The potential for genetic adaptations to language

from Behavioral and Brain Sciences

We suggest there is somewhat more potential than Christiansen & Chater (C&C) allow for genetic adaptations specific to language. Our uniquely cooperative social system requires sophisticated language skills. Learning and performance of some culturally transmitted elements in animals is genetically based, and we give examples of features of human language that evolve slowly enough that genetic adaptations to them may arise.

Gene link to poor reading skills

from the BBC

A common genetic variant may be partly to blame for poor reading ability, research suggests.

Ear Breakthrough Gives Hope To Millions Of Deaf And Hard Of Hearing People

from Medical News Today.com

The latest research, conducted by Dr Jörg T. Albert, a Deafness Research UK research fellow at the UCL Ear Institute, together with scientists at the University of Cologne, shows that fruit flies have ears which mechanically amplify sound signals in a remarkably similar way to the sensory cells found in the inner ear of vertebrates including humans. The finding means that the wealth of genetic techniques already available to study the fruit fly can now be used to target how the ear works.

Genetics of congenital hearing impairment: A clinical approach

from the International Journal of Audiology

Hearing impairment (HI) is the most frequent sensory disorder, with a genetic etiology in >50% of all cases, due to mutations in >44 identified genes. Autosomal recessive inheritance explains the majority, with GJB2 (connexin 26) mutations accounting for 15-50% of paediatric HI. Delayed presentation of HI to 11-60 months in cases of biallelic GJB2 mutations is a concern, necessitating a good audiological follow-up in addition to neonatal hearing screening. Providing a genetic diagnosis in congenital HI has implications for the prognosis, the possible risk of associated medical manifestations, and precise genetic counseling of the family, and should be integrated into the medical examinations done in order to diagnose syndromic features. Large-scale mutation detection methods, such as micro arrays, are promising for wider genetic testing, but few studies on their clinical utility have been published, so far. Limitations of interpretation of genetic test results, combined with significant ethical issues, currently do not justify to institute genetic screening for GJB2 mutations in neonates before a diagnosis of HI is established.

Sudden hearing loss in a family with GJB2 related progressive deafness

from the International Journal of Pediatric Otorhinolaryngology

Mutations of GJB2, the gene encoding connexin 26, have been associated with prelingual, sensorineural hearing loss of mild to profound severity. One specific mutation, the 35delG, has accounted for the majority of mutations detected in the GJB2 gene in Caucasian populations. Recent studies have described progression of hearing loss in a proportion of cases with GJB2 deafness. We report an unusual family with four 35delG homozygous members, in which the parents were deaf-mute whilst both children had a postlingual progressive hearing loss. Furthermore, the son suffered from sudden hearing loss.

Gap junctions and connexins in the inner ear: their roles in homeostasis and deafness

from Current Opinion in Otolaryngology and Head and Neck Surgery

Purpose of review: Mutations in GJB2 and GJB6, the genes encoding the gap-junction proteins connexin 26 and connexin 30, are the most common cause of autosomal recessive nonsyndromic deafness in many populations across the world. In this review, we discuss current ideas about the roles of gap junctions in the inner ear and the implications of connexin mutations on auditory function.

Recent findings: In recent years, a complex picture of the roles of gap junctions in cochlear physiology emerged. Rather than being mere conduits for the circulation of potassium ions in the inner ear, gap junctions have been implicated in intercellular signaling among nonsensory cells and may be involved in the maintenance of the endothelial barrier in the stria vascularis. Studies of mutant channels and mouse models for connexin-related deafness have provided valuable insights into some of the mechanisms by which connexin dysfunction causes cochlear degeneration. They have also identified potential therapeutic interventions for specific connexin mutations, such as the restoration of normal connexin 26 protein levels in GJB6-associated deafness.

Summary: Despite recent advances, a better understanding of the complexity of gap-junctional communication in the inner ear and the structure-function relationships of connexin proteins is required for the development of mechanism-based treatments of connexin-associated hearing loss.

KCNQ4 mutations associated with nonsyndromic progressive sensorineural hearing loss

from Current Opinion in Otolaryngology and Head and Neck Surgery

Purpose of review: This article provides an update on the current progress in identification of KCNQ4 mutations responsible for DFNA2, a subtype of autosomal dominant nonsyndromic progressive hearing loss.

Recent findings: Hearing loss in pateints with DFNA2 usually start at high frequencies in their 20s and 30s, and then progress to more than 60 dB in less than 10 years, with middle and low frequencies often affected as well. To date, eight missense mutations and two deletions of the KCNQ4 gene have been identified in patients with DFNA2 with various clinical phenotypes. In general, missense mutations are associated with younger-onset and all-frequency hearing loss, whereas deletion mutations are underlying later-onset and pure high-frequency hearing loss. The etiology of DFNA2 remains largely unknown at this point, even though the degeneration of cochlear outer hair cells, caused by dysfunction of KCNQ4 channels, might be one of the underlying mechanisms.

Summary: During the last decade, significant progress has been made in identifying KCNQ4 mutations in patients with DFNA2. Elucidation of the pathogenic effect of these mutations will help to gain insights into the molecular mechanisms of hearing and hearing loss, which, in turn, will facilitate informative genetic counseling, early diagnosis, and even treatment of hearing loss.

The tectorial membrane: one slice of a complex cochlear sandwich

from Current Opinion in Otolaryngology and Head and Neck Surgery

Purpose of review: The review is both timely and relevant, as recent findings have shown the tectorial membrane plays a more dynamic role in hearing than hitherto suspected, and that many forms of deafness can result from mutations in tectorial membrane proteins.

Recent findings: Main themes covered are the molecular composition, the structural organization and properties of the tectorial membrane, the role of the tectorial membrane as a second resonator and a structure within which there is significant longitudinal coupling, and how mutations in tectorial membrane proteins cause deafness in mice and men.

Conclusion: Findings from experimental models imply that the tectorial membrane plays multiple, critical roles in hearing. These include coupling elements along the length of the cochlea, supporting a travelling wave and ensuring the gain and timing of cochlear feedback are optimal. The clinical findings suggest stable, moderate-to-severe forms of hereditary hearing loss may be diagnostic of a mutation in TECTA, a gene encoding one of the major, noncollagenous proteins of the tectorial membrane.

Audiological and genetic studies on large families with non-syndromic deafness

from Audiological Medicine

Abstract
Recent progress in gene identification for non-syndromic deafness demonstrates the efficacy of using a large family approach. To assess if clinical and genetic heterogeneity exists in families with non-syndromic hearing impairment we have identified five large Chinese families suitable for investigating clinical and genetic heterogeneity. Five Chinese families spanning 5-6 generations and comprising 48 to 172 members were identified. The auditory phenotype was investigated with pure tone audiometry and DPOAEs. Age at onset of hearing loss was compared between generations by using life-table analysis and the Wilcoxon test in a family. All statistical analyses were performed using the SAS statistical package. Screening for GJB2 and mitochondrial mutations was performed. Two families showing maternal inheritance were found to have the mitDNA A1555G mutation. Subjects with the A1555G mutation exhibit a normal to profound, progressive deafness. Anticipation of the hearing loss was observed in one of these two families. The other three families are segregating for a late onset form of progressive hearing loss with normal vestibular function. DPOAEs from a group of possible gene carriers with normal audiograms in two families have shown a substantial difference from that of controls. Our data show the existence of clinical and genetic heterogeneity in the five large Chinese deaf families. Marked differences in severity of hearing loss, along with a lack of exposure to aminoglycosides and the presence of anticipation in the mitDNA deafness suggest the presence of a modifier. DPOAEs may be a sensitive test for a subclinical change in carriers. Identification of gene(s) for deafness should allow us to better understand the molecular basis of deafness and to improve patient care.

Susceptibility genes for gentamicin-induced vestibular dysfunction

from the Journal of Vestibular Research

Background:Approximately 5% of patients administered gentamicin (GM), an aminoglycoside antibiotic, experience vestibular ototoxicity resulting in balance dysfunction. In the present study, we sought to identify susceptibility genes associated with GM-induced vestibular dysfunction using a case/control design. Methods: White cases (n = 137; 55 men, 82 women) were recruited based on physician-confirmed unilateral or bilateral vestibular dysfunction attributed to GM administration. Controls (n = 126; 54 men, 72 women) were healthy, age-matched individuals without vestibular dysfunction or balance impairment. Buccal cell samples were obtained from all subjects and DNA was genotyped for 15 polymorphisms in 9 genes. Candidate genes were identified primarily for their roles in oxidative stress based on predicted mechanisms of gentamicin-induced ototoxicity. Statistical analyses included the multi-dimensionality reduction (MDR) method for identifying gene x gene interactions across multiple candidate genes. Results: Both single gene and MDR analyses revealed the NOS3 (ENOS) p.Glu298Asp polymorphism as significantly associated with GM-induced vestibular dysfunction (both p

Phenotype/Genotype Correlations in a DFNB1 Cohort With Ethnical Diversity

from Laryngoscope

Abstract:
Objectives/Hypothesis: The aim of this study was to 1) determine the prevalence of DFNB1 in a cohort of children with prelingual nonsyndromic sensorineural hearing loss (HL), 2) study phenotype/genotype correlations, and 3) establish guidelines for genetic counseling of DFNB1.

Study Design: Prospective cohort study.

Methods: A total of 119 unrelated children (107 sporadic and 12 familial cases) with prelingual nonsyndromic HL underwent mutational screening for DFNB1 in the noncoding and coding exons of GJB2, in addition to the del(GJB6-D13S1830) mutation of GJB6. Information regarding demographics, HL, developmental milestones, inner ear high resolution computed tomography, hearing habilitation, and associated phenotypic manifestations were collected in probands with biallelic pathogenic mutations.

Results: The prevalence of DFNB1 in cases of prelingual nonsyndromic HL was 26% (25% in sporadic and 50% in familial cases). In regards to ethnicity, 19 probands were white and 12 probands of Hispanic ancestry had a mixed racial origin (black, Native-American, white). Greater allelic heterogeneity was shown with Hispanics of mixed descent exhibiting 10 of 12 GJB2 allelic variants, whereas whites had 4 of 10 allelic variants (Fisher exact test, P = .033); both ethnic groups had the GJB6 deletion. The frequency of deaf carriers of the most commonly found mutation (c.35delG) was 8% and higher than that of expected for the general population (Fisher exact test, P = .015). The hearing phenotype was variable in terms of degree of impairment (from mild to profound), onset, symmetry and progression, and there was no correlation with any specific genotype class. DFNB1 probands had normal gross motor development, and the frequency of computed tomography abnormalities of the inner ear was low at 8%. No other specific associated phenotypic manifestations were identified.

Conclusions: DFNB1 is the most common identifiable etiology of nonsyndromic prelingual deafness both in sporadic and familial cases in this cohort with ethnic diversity. The greater allelic variability observed in Hispanics and the high frequency of deaf probands carrying a single allelic variant of DFNB1 support extending the screening to noncoding regions of GJB2 and to the remaining DFNB1 locus. Most probands have a congenital HL that is stable, symmetrical and without associated manifestations, but the audiometric profile should not be the only criteria for offering mutational screening of DFNB1 because of the observed variability. These data can be applied to direct the clinical evaluation and effectively counsel families of children with DFNB1.

In Search of the DFNA11 Myosin VIIA Low- and Mid-Frequency Auditory Genetic Modifier

from Otology & Neurotology

Abstract:
Objectives: To evaluate the auditory, vestibular, and retinal characteristics of a large American DFNA11 pedigree with autosomal dominant progressive sensorineural hearing loss that first impacts the low- and mid-frequency auditory range. The pedigree (referred to as the HL2 family) segregates a myosinVIIA (MYO7A) mutation in exon 17 at DNA residue G2164C (MYO7AG2164C) that seems to be influenced by a genetic modifier that either rescues or exacerbates the MYO7AG2164C alteration. DNA analysis to examine single-nucleotide polymorphisms in 2 candidate modifier genes (ATP2B2 and Wolfram syndrome 1 [WFS1]) is summarized in this report.

Study Design: Family study.

Results: The degree of low- and mid-frequency hearing loss in HL2 family members segregating the MYO7AG2164C mutation varies from mild to more severe, with approximately the same number of HL2 family members falling at each end of the severity spectrum. The extent of hearing loss in HL2 individuals can vary between family generations. Differences in the degree of hearing loss in MYO7AG2164C HL2 family members may be mirrored by vestibular function in at least 2 of these same individuals. The single-nucleotide polymorphisms examined within ATP2B2 and WFS1 did not segregate with the mild versus more severe auditory phenotype.

Conclusion: The severity of the auditory and vestibular phenotypes in MYO7AG2164C HL2 family members may run in parallel, suggesting a common modifier gene within the inner ear. The putative MYO7AG2164C genetic modifier is likely to represent a common polymorphism that is not linked tightly to the MYO7A mutation on the MYO7A2164C allele.

Sensory Cell Regeneration and Stem Cells: What We Have Already Achieved in the Management of Deafness

from Otology & Neurotology

Abstract:
Background/Objective: Genetic manipulation of the cell-cycle exit, induction of new hair cells (HCs) through gene modification therapy, and introduction of stem cells (SCs) into damaged cochleas potentially offer exciting new strategies in treating sensorineural hearing loss.

Materials and Methods: Literature review from Medline and database sources.

Study Selection: Ex vivo models, animal studies, in vitro studies, and review articles.

Data Synthesis: Embryonic SCs, neural SCs, or bone marrow SCs survive in the mammalian inner ear after transplantation. The scala media and the modiolus seem more functionally appropriate injection sites. The clear evidence that transplanted neural SCs can adopt the morphologic phenotypes of HCs was the most significant milestone achieved in the related research. The normal cytoarchitecture in the organ of Corti may also be restored through mouse atonal homologue 1 transgene expression and transduction of the nonsensory cells, producing clinically measured improvement in hearing thresholds. Embryonic SC-derived neurons have the potential for synapse formation with auditory HCs and reinnervation of the auditory epithelia. However, fluctuations in survival rates, functional recovery of the spiral-ganglion neurons, integration to the host tissue, and potential immune barriers are also areas of utmost importance.

Conclusion: There is an already exciting progress in the fields of sensory cell regeneration and SC research in an attempt to restore hearing or prevent deafness. However, further understanding of the underlying mechanisms of auditory genetics, continuing investigation of the human genome, refinement of the delivering techniques, and specification of the therapeutic strategies have to be developed before functional regeneration of the cochlea can be achieved in clinical practice.

Feeding and swallowing dysfunction in genetic syndromes

from Developmental Disabilities Research Reviews

Children with genetic syndromes frequently have feeding problems and swallowing dysfunction as a result of the complex interactions between anatomical, medical, physiological, and behavioral factors. Feeding problems associated with genetic disorders may also cause feeding to be unpleasant, negative, or even painful because of choking, coughing, gagging, fatigue, or emesis, resulting in the child to stop eating and to develop behaviors that make it difficult, if not impossible, for a parent to feed their child. In addition, limited experiences with oral intake related to the medical or physical conditions, or other variables such as prematurity, often result in a failure of the child’s oral motor skills to develop normally. For example, a child with Pierre Robin sequence may be unable to successfully feed orally, initially, due to micrognathia and glossoptosis. Oral-motor dysfunction may develop as a result of both anatomical problems, (e.g., cleft lip/palate), lack of experience (e.g., s/p. surgery), or oral motor abnormalities (e.g., brain malformation). Neuromotor coordination impairments such as those associated with Down syndrome (e.g., hypotonia, poor tongue control, and open mouth posture) frequently interfere with the acquisition of effective oral-motor skills and lead to feeding difficulties. Management of these phenomena is frequently possible, if an appropriate feeding plan exist that allows for three primary factors: (1) feeding program must be safe, (2) feeding program must support optimal growth, and (3) feeding program must be realistic. Researchers have demonstrated the utility of behavioral approaches in the treatment of feeding disorders, such as manipulations in the presentation of foods and drink and consequences for food refusal and acceptance (e.g., praise, extinction, contingent access to preferred foods). However, because a child’s failure to eat is not frequently the result of a single cause, evaluation and treatment are typically conducted by an interdisciplinary team usually consisting of a behavioral psychologist, pediatric gastroenterologist, speech pathologist, nutrition, and sometimes other disciplines. This chapter provides an overview of some of the feeding difficulties experience by some of the more common genetic disorders including identification, interventions, and management. © 2008 Wiley-Liss, Inc. Dev Disabil Res Rev 2008;14:147-157.

Spectrum of GJB2 mutations causing deafness in the British Bangladeshi population

from Clinical Otolaryngology

Objective: Mutations in Gap Junction Beta 2 (GJB2) (the gene encoding the protein Connexin 26) have been found to be a major cause of non-syndromic sensorineural recessive deafness. The mutations in GJB2 causing hearing impairment vary in different populations. The aim of this study was to determine the prevalence and spectrum of GJB2 mutations in prelingual deafness in a population of Bangladeshi origin in the UK.

Design: Cross-sectional survey.

Setting: Community based audiology clinic and tertiary level genetics department.

Methods: Fifty-three families (67 patients) with sensorineural hearing loss of unknown cause were included in the study. Detailed history and examination excluded syndromic and environmental causes of hearing loss in the subjects as far as possible. Genetic analysis was performed, specifically looking for mutations in the GJB2 gene.

Results: Of the 53 families, 14 were confirmed to have biallelic pathogenic mutations in GJB2 (26%). The most common mutations of GJB2 in this population were W24X, IVS1+1, M1V, W77X and Q124X, W24X being the most common mutation seen in 57% of patients.

Conclusion: Mutations in GJB2 are responsible for over one quarter of non-syndromic sensorineural deafness in the British Bangladeshi population. It is recommended that all Bangladeshi patients with non-syndromic hearing loss should be first tested for GJB2 mutations before requesting other aetiological investigations.

SLC26A4 c.919-2A>G varies among Chinese ethnic groups as a cause of hearing loss

from Genetics in Medicine

Purpose: Mutations in the SLC26A4 gene are second only to GJB2 mutations as a currently identifiable genetic cause of sensorineural hearing loss. In most areas of China, genetic testing for sensorineural hearing loss is unavailable because of limited knowledge of the mutation spectrum. Although SLC26A4 c.919-2A>G (IVS7-2A>G) is a common mutation among some Asian populations, the mutation prevalence among various ethnic groups within China has not been studied.

Methods: DNA specimens from 3271 subjects with moderate to profound sensorineural hearing loss from 27 regions of China were genotyped for the c.919-2A>G mutation by polymerase chain reaction/restriction-fragment-length polymorphism. Normal hearing controls from Han (n = 185) and Uigur (n = 152) populations were also tested.

Results: Overall, 408 subjects with sensorineural hearing loss (12.5%) carried at least one c.919-2A>G allele, with 158 (4.8%) homozygotes and 250 (7.6%) heterozygotes. Within the subpopulations examined, the rate varies from 0% to 12.2% for c.919-2A>G homozygotes and from 0% to 17.6% for heterozygotes. Based on this cohort, Chinese subjects with sensorineural hearing loss seem to have a relatively higher c.919-2A>G frequency than that of other Asian populations.

Conclusion: These results demonstrate that a simple and efficient genetic test for the c.919-2A>G mutation alone would identify the molecular cause in up to 8-12% of individuals with sensorineural hearing loss in a few eastern and central regions of China. Those who are negative for the c.919-2A>G mutation would be candidates for further mutational analysis of SLC26A4 or other deafness-related genes. This would greatly improve genetic diagnosis and counseling for a huge number of Chinese individuals and family members with sensorineural hearing loss in China, and many more ethnic Chinese in other countries, which might be up to one million.

Birdsong decreases protein levels of FoxP2, a molecule required for human speech

from the Journal of Neurosphysiology

Cognitive and motor deficits associated with language and speech are seen in humans harboring FOXP2 mutations. The neural bases for FOXP2 mutation-related deficits are thought to reside in structural abnormalities distributed across systems important for language and motor learning including the cerebral cortex, basal ganglia and cerebellum. In these brain regions, our prior research showed that FoxP2 mRNA expression patterns are strikingly similar between developing humans and songbirds. Within the songbird brain, this pattern persists throughout life and includes the striatal subregion, Area X, that is dedicated to song development and maintenance. The persistent mRNA expression suggests a role for FoxP2 that extends beyond the formation of vocal learning circuits to their ongoing use. Since FoxP2 is a transcription factor, a role in shaping circuits likely depends upon FoxP2 protein levels which might not always parallel mRNA levels. Indeed, our current study shows that FoxP2 protein, like its mRNA is acutely down-regulated in mature Area X when adult males sing, with some differences. Total corticosterone levels associated with the different behavioral contexts did not vary, indicating that differences in FoxP2 levels are not likely attributable to stress. Our data, together with recent reports on FoxP2’s target genes, suggest that lowered FoxP2 levels may allow for expression of genes important for circuit modification and thus vocal variability.

New Form of Hearing Loss

from Ivanhoe.com

For those who inherited their hearing loss, a new discovery may take away the mystery surrounding their condition. After years of research, scientists have identified a new form of hereditary deafness.

Brief Report: Relationship Between Non-verbal IQ and Gender in Autism

from the Journal of Autism and Developmental Disorders

Abstract It has been proposed that females at risk for autism are protected in some way, so that only those with the greatest genetic liability are affected. Consequently, affected male siblings of females with autism should be more impaired than affected male siblings of male probands. One hundred and ninety-four (194) families with a single child with autism (simplex, SPX) and 154 families with more than one child with autism (multiplex, MPX) were examined on measures of severity, including non-verbal IQ. Among SPX families, girls had lower IQ than boys, but no such differences were seen among MPX families. Similarly, the affected brothers of girls with autism were no different from affected brothers of male probands. These data suggest that MPX and SPX families differ with respect to the relationship between gender and IQ.

Impairments in phonological processing and nonverbal intellectual function in parents of children with autism

from Topix.net

Abstract Language difficulties have been implicated to be a part of the broad autism phenotype in first-degree relatives of individuals with autism.

Genetic and environmental influences on early speech, language and literacy development

from the Journal of Communication Disorders

The genetic and environmental etiology of speech and broader language skills was examined in terms of their concurrent relationships in young children; their longitudinal association with reading; and the role they play in defining the ‘heritable phenotype’ for specific language impairment (SLI). The work was based on a large sample of 4 1/2-year-old twins, who were assessed at home on a broad range of speech and language measures as part of the Twins Early Development Study. We found that genetic factors strongly influence variation in young children’s speech in typical development as well as in SLI, and that these genetic factors also account for much of the relationship between early speech and later reading. In contrast, shared environmental factors play a more dominant role for broader language skills, and in relating these skills to later reading; isolated impairments in language as opposed to speech appear to have largely environmental origins.

Etiologic and Audiologic Evaluations After Universal Neonatal Hearing Screening: Analysis of 170 Referred Neonates

from Pediatrics

OBJECTIVE. The goal was to clarify the audiologic aspects and causes of congenital hearing loss in children who failed universal neonatal hearing screening.

METHODS. A prospective analysis of 170 consecutive records of neonates referred to a tertiary center after universal neonatal hearing screening failure, between 1998 and 2006, was performed. The data presented here represent the equivalent of 87000 screened newborns. The screening results were validated with a clinical ear, nose, and throat examination and electrophysiological testing, including diagnostic auditory brainstem response, automated steady state response, and/or behavioral testing. A diagnostic evaluation protocol for identification of the cause of the hearing loss was also implemented, in collaboration with the departments of genetics and pediatrics.

RESULTS. Permanent hearing loss was confirmed in 116 children (68.2%). Bilateral hearing loss was diagnosed in 68 infants (58.6%) and unilateral hearing loss in 48 infants (41.4%). Median thresholds for the neonates with confirmed hearing loss were severe in both unilateral and bilateral cases, at 70 dB nHL and 80 dB nHL, respectively. In 55.8% of those cases, no risk factors for hearing loss were found. In 60.4%, the initial automated auditory brainstem response diagnosis was totally in agreement with the audiologic evaluation results. In 8.3% of the cases, however, a unilateral refer result was finally classified as bilateral hearing loss. An etiologic factor could be identified in 55.2% of the cases. Of the causes identified, a genetic mechanism was present in 60.4% of the cases, peripartal problems in 20.8%, and congenital cytomegalovirus infection in 18.8%.

CONCLUSIONS. An etiologic factor could be identified for nearly one half of the children with confirmed congenital hearing loss referred through a universal hearing screening program.

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Why Do Preschool Language Abilities Correlate With Later Reading? A Twin Study

from the Journal of Speech, Language, and Hearing Research

Purpose: Language acquisition is predictive of successful reading development, but the nature of this link is poorly understood.

Method: A sample of 7,179 twin pairs was assessed on parent–report measures of syntax and vocabulary at ages 2, 3, and 4 years and on teacher assessments of reading achievement (RA) at ages 7, 9, and 10 years. These measures were used to construct latent factors of early language ability (LA) and RA in structural equation model-fitting analyses.

Results: The phenotypic correlation between LA and RA (r = .40) was primarily due to shared environmental influences that contribute to familial resemblance. These environmental influences on LA and RA overlapped substantially (rC = .62). Genetic influences made a significant but smaller contribution to the phenotypic correlation between LA and RA, and showed moderate overlap (rA = .36). There was also evidence for a direct causal influence of LA on RA.

Conclusions: The association between early language and later reading is underpinned by common environmental and genetic influences. The effects of some risk factors on RA may be mediated by language. The results provide a foundation for more fine-grained studies that examine links between specific measures of language, reading, genes, and environments.

Ethical and social implications of genetic testing for communication disorders

from the Journal of Communication Disorders

Advances in genetics and genomics have quickly led to clinical applications to human health which have far-reaching consequences at the individual and societal levels. These new technologies have allowed a better understanding of the genetic factors involved in a wide range of disorders. During the past decade, incredible progress has been made in the identification of genes involved in the normal process of hearing. The resulting clinical applications have presented consumers with new information and choices. Many of the same gene identification techniques are increasingly being applied to the investigation of complex disorders of speech and language. In parallel with gene identification, studies of the legal, ethical and psychosocial impacts of the clinical application of these advances and their influence on specific behaviors of individuals with communication disorders are paramount, but often lag behind. These studies will help to ensure that new technologies are introduced into clinical practice in a responsible manner.

Is There an Increased Familial Prevalence of Psychopathology in Children With Nonverbal Learning Disorders?

The cognitive and behavioral symptoms of nonverbal learning disabilities (NLD) have been described by previous investigators. Nevertheless, we know far less about the potential genetic contributions that may predispose a child to have NLD. An endophenotype model was investigated in 5 samples of children ages 9 to 15 years: NLD (n = 32); reading disorders (RD; n = 59); participants with a psychiatric diagnosis but without a learning disability (n = 55); typically developing controls (n = 31); and children with velocardiofacial syndrome (VCFS), a chromosomal deletion syndrome that has been proposed as being an exemplar of NLD (VCFS + NLD; n = 20). Based on a family genetic interview, the authors’ data suggest that children with NLD, RD, or a psychiatric diagnosis have a higher prevalence rate of attention-deficit/hyperactivity disorder (ADHD) and substance abuse/dependence. Psychiatric controls and children with NLD—but not children with RD— showed higher prevalence rates of familial bipolar disorder.

Gene expression analysis of human otosclerotic stapedial footplates

from Hearing Research

Otosclerosis is a complex disease that results in a common form of conductive hearing loss due to impaired mobility of the stapes. Stapedial motion becomes compromised secondary to invasion of otosclerotic foci into the stapedio-vestibular joint. Although environmental factors and genetic causes have been implicated in this process, the pathogenesis of otosclerosis remains poorly understood. To identify molecular contributors to otosclerosis we completed a microarray study of otosclerotic stapedial footplates. Stapes footplate samples from otosclerosis and control patients were used in the analysis. One-hundred-and-ten genes were found to be differentially expressed in otosclerosis samples. Ontological analysis of differentially expressed genes in otosclerosis provides evidence for the involvement of a number of pathways in the disease process that include interleukin signaling, inflammation and signal transduction, suggesting that aberrant regulation of these pathways leads to abnormal bone remodeling. Functional analyses of genes from this study will enhance our understanding of the pathogenesis of this disease.

A Novel SLC26A4 (PDS) Deafness Mutation Retained in the Endoplasmic Reticulum

from Archives of Otolaryngology–Head and Neck Surgery

Objectives To identify mutations in the SLC26A4 gene in individuals with nonsyndromic hearing loss and enlarged vestibular aqueduct, to design a predicted model of the pendrin protein, and to characterize novel mutations by means of localization in mammalian cells and effect of the mutation on the predicted model.

Design Validation of the mutation by its exclusion in more than 300 individuals with normal hearing.

Setting A laboratory of genetics of hearing loss research, clinical genetics laboratories, an otolaryngology department at Tel Aviv University, and medical centers in Israel.

Patients A patient with nonsyndromic hearing loss and enlarged vestibular aqueduct, 203 deaf probands, and 310 controls with normal hearing.

Interventions Sequencing the SLC26A4 gene in the patient with nonsyndromic hearing loss and enlarged vestibular aqueduct. Transfection of yellow fluorescent protein (YFP) constructs into mammalian COS7 cells. Designing a computational model of the human SLC26A4 protein.

Main Outcome Measure Detection of a novel c.1458_1459insT SLC26A4 mutation.

Results A computational model of the human pendrin protein suggests that the novel c.1458_1459insT mutation leads to a prematurely truncated protein, p.Ile487TyrfsX39. Mammalian COS7 cells transfected with the YFP-1458_1459insT construct showed mislocalization of the mutant protein.

Conclusions A novel SLC26A4 mutation was detected in Israel. Because current estimates demonstrate that SLC26A4 mutations are involved in up to 4% of nonsyndromic deafness, our findings emphasize the importance of adding a molecular test for the SLC26A4 gene in the diagnosis of deafness, particularly when bone abnormalities are involved, to the list of genes screened in Israel and elsewhere in the world.

Learning Disabilities May Presage Later Language Problems

from MedicineNet.com

TUESDAY, Feb. 12 (HealthDay News) — People with a personal or family history of learning disabilities may be more at risk for a rare type of dementia that causes them to lose language abilities as they age, according to a new report.

Factors Affecting Articulation Skills In Children With Velocardiofacial Syndrome and Children With Cleft Palate or Velopharyngeal Dysfunction: A Preliminary Report

from the Cleft Palate-Craniofacial Journal

Objective: To examine the influence of speech perception, cognition, and implicit phonological learning on articulation skills of children with velocardiofacial syndrome (VCFS) and children with cleft palate or velopharyngeal dysfunction (VPD).

Design: Cross-sectional group experimental design.

Participants: Eight children with VCFS and five children with nonsyndromic cleft palate or VPD.

Methods and Measures: All children participated in a phonetic inventory task, speech perception task, implicit priming nonword repetition task, conversational sample, nonverbal intelligence test, and hearing screening. Speech tasks were scored for percentage of phonemes correctly produced. Group differences and relations among measures were examined using nonparametric statistics.

Results: Children in the VCFS group demonstrated significantly poorer articulation skills and lower standard scores of nonverbal intelligence compared with the children with cleft palate or VPD. There were no significant group differences in speech perception skills. For the implicit priming task, both groups of children were more accurate in producing primed nonwords than unprimed nonwords. Nonverbal intelligence and severity of velopharyngeal inadequacy for speech were correlated with articulation skills.

Conclusions: In this study, children with VCFS had poorer articulation skills compared with children with cleft palate or VPD. Articulation difficulties seen in the children with VCFS did not appear to be associated with speech perception skills or the ability to learn new phonological representations. Future research should continue to examine relationships between articulation, cognition, and velopharyngeal dysfunction in a larger sample of children with cleft palate and VCFS.

Successful cochlear implantation in a child with Keratosis, Icthiosis and Deafness (KID) Syndrome and Dandy-Walker malformation

from the International Journal of Pediatric Otorhinolaryngology

Keratosis, Icthiosis, and Deafness (KID) Syndrome is a rare congenital disorder associated with dominant connexin 26 mutations, affecting epidermis, corneal epithelium, and inner ear. Given eventual visual impairment, cochlear implantation is an important consideration despite an increased risk of wound complications. We present a child with KID Syndrome and bilateral profound sensorineural hearing loss associated with a novel heterozygous missense D50A connexin 26 mutation (c.149A > C). Imaging revealed mild cochlear malformation and Dandy-Walker malformation. She received a cochlear implant at the age of 12 months, using a small incision approach. Following an immediate minor wound infection, implantation has been successful without further complication over 4 years.