Connexin-30 deletion analysis in connexin-26 heterozygotes

Mutations in the Connexin-26 gene (Cx 26, GJB2) are the most common cause of hereditary nonsyndromic sensorineural hearing loss (SNHL). DNA analysis of the Cx 26 gene in deaf or hard-of-hearing individuals frequently demonstrates heterozygosity despite the fact that most mutations are known to be recessive. A 342-kb deletion in a gene adjacent to Cx 26, the Connexin-30 gene (Cx 30, GJB6), has been reported to cause deafness in the homozygous state or in combination with heterozygous mutations in Cx 26 (digenic inheritance). We have analyzed deaf or hard-of-hearing Cx 26 heterozygotes and individuals with no mutations in Cx 26 for this Cx 30 deletion. We found that 4/20 (20%) of the Cx 26 heterozygotes are heterozygous for this deletion and that no individuals were homozygous for the Cx 30 deletion. Cx 30 deletion analysis is recommended for all individuals with nonsyndromic SNHL following Cx 26 sequencing that does not demonstrate two recessive mutations.     

Attitudes of deaf adults toward genetic testing for hereditary deafness.

Recent advances within molecular genetics to identify the genes for deafness mean that it is now possible for genetic-counseling services to offer genetic testing for deafness to certain families. The purpose of this study is to document the attitudes of deaf adults toward genetic testing for deafness. A structured, self-completion questionnaire was given to delegates at an international conference on the "Deaf Nation," held at the University of Central Lancashire in 1997. The conference was aimed at well-educated people, with an emphasis on Deaf culture issues. Eighty-seven deaf delegates from the United Kingdom returned completed questionnaires. The questionnaire had been designed to quantitatively assess attitudes toward genetics, interest in prenatal diagnosis (PND) for deafness, and preference for having deaf or hearing children. The results from this study provide evidence of a predominantly negative attitude toward genetics and its impact on deaf people, in a population for whom genetic-counseling services are relevant. Fifty-five percent of the sample thought that genetic testing would do more harm than good, 46% thought that its potential use devalued deaf people, and 49% were concerned about new discoveries in genetics. When asked about testing in pregnancy, 16% of participants said that they would consider having PND, and, of these, 29% said that they would prefer to have deaf children. Geneticists need to appreciate that some deaf persons may prefer to have deaf children and may consider the use of genetic technology to achieve this. Any genetic-counseling service set up for families with deafness can only be effective and appropriate if clinicians and counselors take into consideration the beliefs and values of the deaf community at large.     

Connexin-26 gene analysis in hearing-impaired newborns

The efficacy and utility of the Connexin-26 (Cx-26) gene (also called GJB2) analysis from DNA isolated from Guthrie newborn screening cards is demonstrated. This analysis precisely defined a major cause of prelingual nonsyndromic deafness in those children requiring amplification in our study. Guthrie cards were obtained from 49 deaf children requiring amplification identified over the last 5 years by the Rhode Island Newborn Screening Program. Children with syndromes or other recognizable causes of hearing loss were excluded. DNA was extracted from the Guthrie cards and analyzed sequentially for the Cx-26 35delG mutation and then for the 167delT mutation followed by gene sequencing on remaining heterozygotes. Three of 42 children were 35delG homozygotes; 2/42 children were 35delG/167delT compound heterozygotes. One child was identified as being a 35delG heterozygote with no other mutation found by sequencing. Nine Guthrie cards yielded no amplification or uninterpretable results. Cx-26 mutations were identified as causing 11.9% of the deafness in the children studied. In conclusion, Cx-26 analysis is an important test that identifies a major cause of prelingual nonsyndromic deafness. Molecular analysis of hearing-impaired newborns will be important for genetic counseling in these families. Failures with Guthrie cards may make use of other collection methods preferable.     

Haptic Spatial Configuration Learning in Deaf and Hearing Individuals

The present study investigated haptic spatial configuration learning in deaf individuals, hearing sign language interpreters and hearing controls. In three trials, participants had to match ten shapes haptically to the cut-outs in a board as fast as possible. Deaf and hearing sign language users outperformed the hearing controls. A similar difference was observed for a rotated version of the board. The groups did not differ, however, on a free relocation trial. Though a significant sign language experience advantage was observed, comparison to results from a previous study testing the same task in a group of blind individuals showed it to be smaller than the advantage observed for the blind group. These results are discussed in terms of how sign language experience and sensory deprivation benefit haptic spatial configuration processing.     

Effect of Exogenous Cues on Covert Spatial Orienting in Deaf and Normal Hearing Individuals

Deaf individuals have been known to process visual stimuli better at the periphery compared to the normal hearing population. However, very few studies have examined attention orienting in the oculomotor domain in the deaf, particularly when targets appear at variable eccentricity. In this study, we examined if the visual perceptual processing advantage reported in the deaf people also modulates spatial attentional orienting with eye movement responses. We used a spatial cueing task with cued and uncued targets that appeared at two different eccentricities and explored attentional facilitation and inhibition. We elicited both a saccadic and a manual response. The deaf showed a higher cueing effect for the ocular responses than the normal hearing participants. However, there was no group difference for the manual responses. There was also higher facilitation at the periphery for both saccadic and manual responses, irrespective of groups. These results suggest that, owing to their superior visual processing ability, the deaf may orient attention faster to targets. We discuss the results in terms of previous studies on cueing and attentional orienting in deaf.     

Intersecting Cultures in Deaf Mental Health: An Ethnographic Study of NHS Professionals Diagnosing Autism in D/deaf Children

Autism assessments for children who are deaf are particularly complex for a number of reasons, including overlapping cultural and clinical factors. We capture this in an ethnographic study of National Health Service child and adolescent mental health services in the United Kingdom, drawing on theoretical perspectives from transcultural psychiatry, which help to understand these services as a cultural system. Our objective was to analyse how mental health services interact with Deaf culture, as a source of cultural-linguistic identity. We ground the study in the practices and perceptions of 16 professionals, who have conducted autism assessments for deaf children aged 0–18. We adopt a framework of intersectionality to capture the multiple, mutually enforcing factors involved in this diagnostic process. We observed that professionals working in specialist Deaf services, or with experience working with the Deaf community, had intersectional understandings of assessments: the ways in which cultural, linguistic, sensory, and social factors work together to produce diagnoses. Working with a diagnostic system that focuses heavily on ‘norms’ based on populations from a hearing culture was a key source of frustration for professionals. We conclude that recognising the intersectionality of mental health and Deaf culture helps professionals provide sensitive diagnoses that acknowledge the multiplicity of D/deaf experiences.     

Information needs of mothers regarding communicating BRCA1/2 cancer genetic test results to their children

Mothers who participate in genetic testing for hereditary breast/ovarian cancer risk must decide if, when, and how to ultimately share their BRCA1 and BRCA2 (BRCA1/2) test results with their minor-age children. One of the primary aides for mothers in making this decision is cancer genetic counseling. However, counseling is limited in how well it can educate mothers about such decisions without the availability of resources that are specific to family communication and genetic testing per se. In an effort to fill this gap and identify mothers most likely to benefit from such resources, surveys were conducted with 187 mothers undergoing BRCA1/2 testing who had children 8-21 years old. Data were collected weeks after genetic testing but prior to mothers' learning of their test results; quantitative assessments of informational resource needs (i.e., speaking with previous BRCA1/2 testing participants who are parents regarding their experiences, reading educational literature about options and what to expect, speaking with a family counselor, attending a family support group, and self-nominated other resources), testing motivations, decision making vigilance, and decisional conflict regarding communicating test results to children were included. Mothers' most-to-least frequently cited information resource needs were: literature (93.4%), family counseling (85.8%), prior participants (79.0%), support groups (53.9%), and other (28.9%; e.g., pediatricians and psychologists). Seventy-eight percent of mothers were interested in accessing three or more resources. In multivariate regression analyses, testing motivations (beta = 0.35, p = 0.03), decision-making vigilance (beta = 0.16, p = 0.00), and decisional conflict (beta = 0.10, p = 0.00) were associated with mothers' need level; mothers with a greater interest in testing to learn about their children's risks, those with more vigilant decision-making styles, and those with higher decisional conflict had the greatest need. In conjunction with enhanced genetic counseling focusing on family disclosure, educational literature, and psychosocial support may promote improved outcomes.     

Multiplex detection of common mutations in the Connexin-26 gene

Hearing impairment that results from inherited genetic defects occurs in approximately 1/2,000 live births. Mutations in the Connexin-26 gene have been shown to be a major contributor to prelingual, nonsyndromic, autosomal recessive deafness in many populations. The most common mutations in this gene are 35delG, 167delT, 235delC, M34T, and W77X. We describe a nonisotopic, single-tube, polymerase chain reaction (PCR) multiplex system for the detection of these common mutations. The method presented is reliable, simple, and low in cost.     

High incidence of profound deafness in an isolated community

In a Muslim Israeli Arab village, different types of hearing loss affect some 2% of the inhabitants. Most cases of profound deafness are due to recessive mutations in the Connexin-26 gene. Since in this community, marriages are by preference within the family (consanguineous), for many of the couples from the village the risk for an affected child is high. There are 30 families living in the village in which both parents have normal hearing and at least one child has a profound hearing defect. In these families, the birth of a child with profound deafness did not change family planning. The rate of marriage was similar for the siblings of deaf children as for other individuals in the village. The major problems were encountered by the deaf individuals themselves; in particular, most of the women were not married. Because of the distinctive nature of this particular problem, different types of screening programs were envisaged. However, all of them are problematic. Therefore, as a first step it was decided to begin a program including individual genetic counseling together with education of the entire population on practical aspects of human genetics.     

Parental attitudes toward genetic testing for pediatric deafness

Recent molecular genetic advances have resulted in genetic testing becoming an option for deaf individuals and their families. However, there is little information about the interest in such testing. To investigate this issue, parents with normal hearing who have one or more deaf children were surveyed about their attitudes toward diagnostic, carrier, and prenatal genetic testing for deafness. This population was chosen because it represents the majority of individuals who are encountered in clinical practice, given that 90%-95% of deaf individuals are born to persons with normal hearing. Of 328 surveys distributed, 96 were completed and returned. Of the respondents, 96% recorded a positive attitude toward genetic testing for deafness, including prenatal testing, although none would use this information to terminate an affected pregnancy. All respondents had a poor understanding of genetics, with 98% both incorrectly estimating the recurrence risk of deafness and misunderstanding the concept of inheritance. Notably, these findings were similar in the group who had had genetic testing for their children and in the group who had not, suggesting either that the parents who received genetic testing did not receive genetic counseling or that the counseling was not effective. On the basis of these results, it was concluded that this population is interested in the use of genetic testing and that testing should not be done without first providing formal genetic counseling. Appropriate counseling can help parents to understand the risks, benefits, and limitations of genetic testing.     

Professional and personal attitudes about access and confidentiality in the genetic testing of children: a pilot study

The ability to perform predictive genetic testing of children raises ethical concerns regarding whether and when to test and the disclosure of results. Semi-structured interviews with a convenience sample of pediatricians (12) and geneticists (13) were conducted to see how they would react to parental requests for predictive genetic testing of their children, and their attitudes about testing their own children. We also asked about disclosure attitudes and practices for their patients' relatives and within their own families. Respondents would provide predictive genetic testing for most conditions, yet were less likely to seek this information about their own children. Respondents believed it was very important for patients to share some types of genetic information with relatives, and were directive in their counseling about intrafamilial disclosure, especially within their own families. Although respondents would almost never breach patient confidentiality, many would breach confidentiality within their own families. Health care professionals distinguish between their professional and personal roles with regard to issues of access and confidentiality in predictive testing of children. They are willing to provide greater access and more confidentiality for their patients than within their own families.     

人工耳蜗植入聋儿术前基因检测及家系分析

摘要: 国内外研究表明GJB2、SLC26A4(PDS)和线粒体DNA(Mitochondrial DNA, mtDNA)的病理性突变导致了大部分的遗传性聋。 文章收集了2006年4月~2007年9月接受人工耳蜗(Cochlear implant, CI)植入的14 例患儿及其父母的外周血, 应用基因诊断方法进行 GJB2、SLC26A4(PDS)和mtDNA 1555位点突变检测。结果显示, 35.7%的患儿检测到致病突变, 其中28.6%为GJB2基因突变, 类型均为235delC纯和突变, 其父母为携带GJB2 235delC的杂和子; 7.1%为mtDNA A1555G突变, 其母亲亦携带mtDNA A1555G突变。这表明CI 植入聋儿最常见的基因突变是GJB2 235delC突变, 其次是mtDNA A1555G突变, 通过对耳聋家系常见致病基因的检测和家系分析, 可以对优生优育及减少耳聋发病率提供科学准确的遗传信息。     

Factors determining dissemination of results and uptake of genetic testing in families with known BRCA1/2 mutations

BACKGROUND: Uptake of genetic testing remains low, even in families with known BRCA1 and BRCA2 (BRCA1/2) mutations, despite effective interventions to reduce risk. We report disclosure and uptake patterns by BRCA1/2-positive individuals to at-risk relatives, in the setting of no-cost genetic counseling and testing. METHODS: Relatives of BRCA1/2-positive individuals were offered cost-free and confidential genetic counseling and testing. If positive for a BRCA1/2 mutation, participants were eligible to complete a survey about their disclosure of mutation status and the subsequent uptake of genetic testing by at-risk family members. RESULTS: One hundred and fifteen of 142 eligible individuals responded to the survey (81%). Eighty-eight (77%) of those surveyed disclosed results to all at-risk relatives. Disclosure to first-degree relatives (FDRs) was higher than to second-degree relatives (SDRs) and third-degree relatives (TDR) (95% vs. 78%; p < 0.01). Disclosure rates to male versus female relatives were similar, but reported completion of genetic testing was higher among female versus male FDRs (73% vs. 49%; p < 0.01) and SDRs (68% vs. 43%; p < 0.01), and among members of maternal versus paternal lineages (63% vs. 0%; p < 0.01). Men were more likely than women to express general difficulty discussing positive BCRA1/2 results with at-risk family members (90% vs. 70%; p = 0.03), while women reported more emotional distress associated with disclosure than men (48% vs. 13%; p < 0.01). DISCUSSION: We report a very high rate of disclosure of genetic testing information to at-risk relatives. However, uptake of genetic testing among at-risk individuals was low despite cost-free testing services, particularly in men, SDRs, and members of paternal lineages. The complete lack of testing among paternally related at-risk individuals and the lower testing uptake among men signify a significant barrier to testing and a challenge for genetic counselors and physicians working with high-risk groups. Further research is necessary to ensure that family members understand their risk and the potential benefits of genetic counseling.     

Genetic tests obtainable through pharmacies: the good,the bad,and the ugly

Genomic medicine seeks to exploit an individual’s genomic information in the context of guiding the clinical decision-making process. In the post-genomic era, a range of novel molecular genetic testing methodologies have emerged, allowing the genetic testing industry to grow at a very rapid pace. As a consequence, a considerable number of different private diagnostic testing laboratories now provide a wide variety of genetic testing services, often employing a direct-to-consumer (DTC) business model to identify mutations underlying (or associated with) common Mendelian disorders, to individualize drug response, to attempt to determine an individual’s risk of a multitude of complex (multifactorial) diseases, or even to determine a person’s identity. Recently, we have noted a novel trend in the provision of private molecular genetic testing services, namely saliva and buccal swab collection kits (for deoxyribonucleic acid (DNA) isolation) being offered for sale over the counter by pharmacies. This situation is somewhat different from the standard DTC genetic testing model, since pharmacists are healthcare professionals who are supposedly qualified to give appropriate advice to their clients. There are, however, a number of issues to be addressed in relation to the marketing of DNA collection kits for genetic testing through pharmacies, namely a requirement for regulatory clearance, the comparative lack of appropriate genetics education of the healthcare professionals involved, and most importantly, the lack of awareness on the part of both the patients and the general public with respect to the potential benefits or otherwise of the various types of genetic test offered, which may result in confusion as to which test could be beneficial in their own particular case. We believe that some form of genetic counseling should ideally be integrated into, and made inseparable from, the genetic testing process, while pharmacists should be obliged to receive some basic training about the genetic tests that they offer for sale.     

Genetic testing for hemochromatosis: attitudes and acceptability among young and older adults

Hemochromatosis is a genetic disorder of iron overload common in persons of northern European descent. We examined attitudes about testing for hemochromatosis in 118 young adults (YA) (19.7 years +/- 1.9) and 50 older adults (OA) (58.5 years +/- 13.7). Participants read about hemochromatosis and two related tests: transferrin saturation measurement (iron test) and HFE genotyping (HFE test). Interest in each test and attitudes about genetic testing were assessed. More than 80% of all participants were willing to undergo either test, if offered. A majority preferred the iron test because of the information it provides about current health. A majority of participants identified at least one benefit of genetic testing, with improved health through early detection/prevention being most common. YA were more likely to report disadvantages of genetic testing (p < 0.001) and were more concerned about potential negative psychological effects (p < 0.005). OA were more concerned about potential discrimination (p < 0.0001). These findings suggest that young and older adults view genetic testing as beneficial and would accept HFE testing were it offered as part of a screening program.     

Low Empathy in Deaf and Hard of Hearing (Pre)Adolescents Compared to Normal Hearing Controls

Objective

The purpose of this study was to examine the level of empathy in deaf and hard of hearing (pre)adolescents compared to normal hearing controls and to define the influence of language and various hearing loss characteristics on the development of empathy.

Methods

The study group (mean age 11.9 years) consisted of 122 deaf and hard of hearing children (52 children with cochlear implants and 70 children with conventional hearing aids) and 162 normal hearing children. The two groups were compared using self-reports, a parent-report and observation tasks to rate the children’s level of empathy, their attendance to others’ emotions, emotion recognition, and supportive behavior.

Results

Deaf and hard of hearing children reported lower levels of cognitive empathy and prosocial motivation than normal hearing children, regardless of their type of hearing device. The level of emotion recognition was equal in both groups. During observations, deaf and hard of hearing children showed more attention to the emotion evoking events but less supportive behavior compared to their normal hearing peers. Deaf and hard of hearing children attending mainstream education or using oral language show higher levels of cognitive empathy and prosocial motivation than deaf and hard of hearing children who use sign (supported) language or attend special education. However, they are still outperformed by normal hearing children.

Conclusions

Deaf and hard of hearing children, especially those in special education, show lower levels of empathy than normal hearing children, which can have consequences for initiating and maintaining relationships.     

Examining Interactions across Language Modalities: Deaf Children and Hearing Peers at School

Deaf youth easily become communicatively isolated in public schools, where they are in a small minority among a majority of hearing peers and teachers. This article examines communicative strategies of deaf children in an American "mainstream " school setting to discover how they creatively manage their casual communicative interactions with hearing peers across multimodal communicative channels, visual and auditory. We argue that unshared sociolinguistic practices and hearing-oriented participation frameworks are crucial aspects of communicative failure in these settings. We also show that what look like "successful" conversational interactions between deaf and hearing children actually contain little real language and few of the complex communication skills vital to cognitive and social development. This study contributes to understanding the social production of communicative isolation of deaf students and implications of mainstream education for this minority group.     

Genetic diversity and relationships among the tribes of Meghalaya compared to other Indian and Continental populations

The autosomal AmpFLSTR markers validated and widely used for forensic applications are used in this study to examine the extent of diversity and genetic relationships among nine Meghalaya populations. Altogether, 932 chromosomes from 9 populations were analyzed using 9 tetrameric AmpFLSTR loci. The included populations were all seven subtribes of the Austro-Asiatic Mon-Khmer-speaking Khasi and the neighboring Tibeto-Burman Garo. The Lyngngam, which are linguistically closer to the Khasi but are culturally intermediate between the Khasi and the Garo, are also included in the study. Although most of the microsatellite loci are highly polymorphic in each of these populations, the allele distributions are fairly uniform across the Meghalaya populations, suggesting relative homogeneity among them. Concurrent with this, the coefficient of gene differentiation (G(ST)) is observed to be low (0.026+/-0.002). This is naturally reflected in the lack of clear differentiation and clustering pattern of the Meghalaya tribes based on either geographic proximity or the historical or current affiliations of these tribes. Analysis of molecular variance (AMOVA) suggests no significant population structure. The structure analysis further suggests that, barring War-Khasi and Pnar, no other population shows any semblance of genetic identity. Even the position of the linguistically distinct Garo is not portrayed as separate from the Khasi. However, when comparable data from other Indian, Southeast Asian, and other continental populations were analyzed, the Meghalaya populations formed a compact cluster clearly separated from other populations, suggesting genetic identity of the Meghalaya populations as a whole. These results are concurrent with the hypothesis of a common and recent origin of these Meghalaya populations, whose genetic differentiation is overwhelmed by the homogenizing effect of continuous gene flow.     

The Double Helix: Applying an Ethic of Care to the Duty to Warn Genetic Relatives of Genetic Information

Genetic testing reveals information about a patient's health status and predictions about the patient's future wellness, while also potentially disclosing health information relevant to other family members. With the increasing availability and affordability of genetic testing and the integration of genetics into mainstream medicine, the importance of clarifying the scope of confidentiality and the rules regarding disclosure of genetic findings to genetic relatives is prime. The United Nations International Declaration on Human Genetic Data urges an appreciation for principles of equality, justice, solidarity and responsibility in the context of genetic testing, including a commitment to honoring the privacy and security of the person tested. Considering this global mandate and recent professional statements in the context of a legal amendment to patient privacy policies in Australia, a fresh scrutiny of the legal history of a physician's duty to warn is warranted. This article inquiries whether there may be anything ethically or socially amiss with a potential future recommendation for health professionals or patients to universally disclose particular cancer predisposition genetic diagnosis to genetic family members. While much of the discussion remains applicable to all genetic diagnosis, the article focuses on the practice of disclosure within the context of BRCA1/2 diagnosis. An ‘ethic of care’ interpretation of legal tradition and current practice will serve to reconcile law and medical policy on the issue of physician disclosure of genetic results to family members without patient consent.     

Visual advantage in deaf adults linked to retinal changes

The altered sensory experience of profound early onset deafness provokes sometimes large scale neural reorganisations. In particular, auditory-visual cross-modal plasticity occurs, wherein redundant auditory cortex becomes recruited to vision. However, the effect of human deafness on neural structures involved in visual processing prior to the visual cortex has never been investigated, either in humans or animals. We investigated neural changes at the retina and optic nerve head in profoundly deaf (N = 14) and hearing (N = 15) adults using Optical Coherence Tomography (OCT), an in-vivo light interference method of quantifying retinal micro-structure. We compared retinal changes with behavioural results from the same deaf and hearing adults, measuring sensitivity in the peripheral visual field using Goldmann perimetry. Deaf adults had significantly larger neural rim areas, within the optic nerve head in comparison to hearing controls suggesting greater retinal ganglion cell number. Deaf adults also demonstrated significantly larger visual field areas (indicating greater peripheral sensitivity) than controls. Furthermore, neural rim area was significantly correlated with visual field area in both deaf and hearing adults. Deaf adults also showed a significantly different pattern of retinal nerve fibre layer (RNFL) distribution compared to controls. Significant correlations between the depth of the RNFL at the inferior-nasal peripapillary retina and the corresponding far temporal and superior temporal visual field areas (sensitivity) were found. Our results show that cross-modal plasticity after early onset deafness may not be limited to the sensory cortices, noting specific retinal adaptations in early onset deaf adults which are significantly correlated with peripheral vision sensitivity.