Oculoauriculovertebral spectrum: report of nine familial cases with evidence of autosomal dominant inheritance and review of the literature

Oculoauriculovertebral spectrum (OAVS; OMIM 164210) is a complex condition characterized by defects of aural, oral, mandibular and vertebral development. The aetiology of this condition is likely to be heterogeneous; most cases are sporadic, however, familial cases suggesting autosomal recessive end autosomal dominant inheritance have been reported. In this study, we describe the clinical aspects of nine familial cases with evidence of autosomal dominant inheritance and compare them with reports in the literature. Interfamilial and intrafamilial clinical variabilities were observed in this study (reinforcing the necessity of careful examination of familial members). We suggest that oculoauriculovertebral spectrum with autosomal dominant inheritance is characterized mainly by bilateral auricular involvement and rarely presents extracranial anomalies. Clin Dysmorphol 18:67-77 (C) 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins.

The search of a genetic basis for noise-induced hearing loss (NIHL)

Background and aim: Knowledge about the genetic factors responsible for noise-induced hearing loss (NIHL) is still limited. This study investigated whether genetic factors are associated or not to susceptibility to NIHL. Subjects and methods: The family history and genotypes were studied for candidate genes in 107 individuals with NIHL, 44 with other causes of hearing impairment and 104 controls. Mutations frequently found among deaf individuals were investigated (35delG, 167delT in GJB2, Delta(GJB6- D13S1830), Delta(GJB6- D13S1854) in GJB6 and A1555G in MT-RNR1 genes); allelic and genotypic frequencies were also determined at the SNP rs877098 in DFNB1, of deletions of GSTM1 and GSTT1 and sequence variants in both MTRNR1 and MTTS1 genes, as well as mitochondrial haplogroups. Results: When those with NIHL were compared with the control group, a significant increase was detected in the number of relatives affected by hearing impairment, of the genotype corresponding to the presence of both GSTM1 and GSTT1 enzymes and of cases with mitochondrial haplogroup L1. Conclusion: The findings suggest effects of familial history of hearing loss, of GSTT1 and GSTM1 enzymes and of mitochondrial haplogroup L1 on the risk of NIHL. This study also described novel sequence variants of MTRNR1 and MTTS1 genes.

Role of the Mitochondrial Mutations, m. 827A > G and the Novel m. 7462C > T, in the Origin of Hearing Loss

Samples from 30 deaf probands exhibiting features suggestive of syndromic mitochondrial deafness or from families with maternal transmission of deafness were selected for investigation of mutations in the mitochondrial genes MT-RNR1 and MT-TS1. Patients with mutation m. 1555A>G had been previously excluded from this sample. In the MT-RNR1 gene, five probands presented the m. 827A>G sequence variant, of uncertain pathogenicity. This change was also detected in 66 subjects of an unaffected control sample of 306 Brazilian individuals from various ethnic backgrounds. Given its high frequency, we consider it unlikely to have a pathogenic role on hereditary deafness. As to the MT-TS1 gene, one proband presented the previously known pathogenic m. 7472insC mutation and three probands presented a novel variant, m. 7462C>T, which was absent from the same control sample of 306 individuals. Because of its absence in control samples and association with a family history of hearing impairment, we suggest it might be a novel pathogenic mutation.

Mandibulofacial Dysostosis, Severe Lower Eyelid Coloboma, Cleft Palate, and Alopecia: A New Distinct Form of Mandibulofacial Dysostosis or a Severe Form of Johnson-McMillin Syndrome?

We describe a patient with a phenotype characterized by mandibulofacial dysostosis with severe lower eyelid coloboma, cleft palate, abnormal ears, alopecia, delayed eruption and crowded teeth, and sensorioneural hearing loss. The karyotype and the screening for mutations in the coding region of TCOF1 gene were normal. The clinical signs of our case overlap the new mandibulofacial dysostosis described by Stevenson et al. [2007] and the case with Johnson-McMillin syndrome described by Cushman et al. [2005]. The similar clinical signs, mainly, the severe facial involvement observed in these cases suggest that they can represent a new distinct form of mandibulofacial dysostosis or the end of the spectrum of Johnson McMillin syndrome. (C) 2010 Wiley-Liss, Inc.

Chromosome imbalances in syndromic hearing loss

The cause of hearing impairment has not been elucidated in a large proportion of patients. We screened by 1-Mb array-based comparative genomic hybridization (aCGH) 29 individuals with syndromic hearing impairment whose clinical features were not typical of known disorders. Rare chromosomal copy number changes were detected in eight patients, four de novo imbalances and four inherited from a normal parent. The de novo alterations define candidate chromosome segments likely to harbor dosage-sensitive genes related to hearing impairment, namely 1q23.3-q25.2, 2q22q23, 6p25.3 and 11q13.2-q13.4. The rare imbalances also present in normal parents might be casually associated with hearing impairment, but its role as a predisposition gene remains a possibility. Our results show that syndromic deafness is frequently associated with chromosome microimbalances (14-27%), and the use of aCGH for defining disease etiology is recommended.

Prevalence of GJB2 (Connexin-26) and GJB6 (Connexin-30) Mutations in a Cohort of 300 Brazilian Hearing-Impaired Individuals: Implications for Diagnosis and Genetic Counseling

Objective: Hereditary nonsyndromic deafness is an autosomal recessive condition in about 80% of cases, and point mutations in the GJB2 gene (connexin 26) and two deletions in the GJB6 gene (connexin 30), del(GJB6-D13S1830) and del(GJB6-D13S1854), are reported to account for 50% of recessive deafness, Aiming at establishing the frequencies of GJB2 mutations and GJB6 deletions in the Brazilian population, we screened 300 unrelated individuals with hearing impairment, who were not affected by known deafness related syndromes. Methods: We firstly screened the most frequently reported mutations, c.35delG and c.167delT in the GJB2 gene, and del(GJB6-D13S1830) and del(GJB6-D13S1854) in the GJB6 gene, through specific techniques. The detected c.35delG and c.167delT mutations were validated by sequencing. Other mutations in the GJB2 gene were screened by single-strand conformation polymorphism and the coding region was sequenced when abnormal patterns were found. Results: Pathogenic mutations in GJB2 and GJB6 genes were detected in 41 individuals (13.7%), and 80.5% (33/41) presented these mutations in homozygosis or compound heterozygosis, thus explaining their hearing defect. The c.35delG in the GJB2 gene was the most frequent mutation (37/300; 12.4%), detected in 23% familial and 6.2% the sporadic cases. The second most frequent mutation (1%; 3/300) was the del(GJB6- D13S1830), always found associated with the c.35delG mutation. Nineteen different sequence variations were found in the GJB2 gene. In addition to the c.35delG mutation, nine known pathogenic alterations were detected 0 67delT, p.Trp24X, p.Val37lle, c.176_191del16, c.235delC, p.Leu90Pro, p.Arg127His, c.509insA, and p.Arg184Pro, Five substitutions had been previously considered benign polymorphisms: c.-15C>T, p.Val27lle, p.Met34hr, p.Ala40Ala, and p.Gly160Ser. Two previously reported Mutations of unknown pathogenicity were found (p.Lys168Arg, and c.684C>A), and two novel substitutions, p.Leu81Val (c.G241C) and p.Met195Val (c.A583G), both in heterozygosis without an accompanying mutation in the other allele. None of these latter four variants of undefined status was present in a sample of 100 hearing controls. Conclusions: The present study demonstrates that Mutations in the GJB2 gene and del(GJB6 D13S1830) are important causes of hearing impairment in Brazil, thus justifying their screening in a routine basis. The diversity of variants in our sample reflects the ethnic heterogeneity of the Brazilian population.

Novel OTOF mutations in Brazilian patients with auditory neuropathy

The OTOF gene encoding otoferlin is associated with auditory neuropathy (AN), a type of non-syndromic deafness. We investigated the contribution of OTOF mutations to AN and to non-syndromic recessive deafness in Brazil. A test for the Q829X mutation was carried out on a sample of 342 unrelated individuals with non-syndromic hearing loss, but none presented this mutation. We selected 48 cases suggestive of autosomal recessive inheritance, plus four familial and seven isolated cases of AN, for genotyping of five microsatellite markers linked to the OTOF gene. The haplotype analysis showed compatibility with linkage in 11 families (including the four families with AN). Samples of the 11 probands from these families and from seven isolated cases of AN were selected for an exon-by-exon screening for mutations in the OTOF gene. Ten different pathogenic variants were detected, among which six are novel. Among the 52 pedigrees with autosomal recessive inheritance (including four familial cases of AN), mutations were identified in 4 (7.7%). Among the 11 probands with AN, seven had at least one pathogenic mutation in the OTOF gene. Mutations in the OTOF gene are frequent causes of AN in Brazil and our results confirm that they are spread worldwide. Journal of Human Genetics (2009) 54, 382-385; doi: 10.1038/jhg.2009.45; published online 22 May 2009

Deaf education and underlying structures of power in communication

This article argues that claims of diversity in communication in deaf education are empty rhetoric when underlying structures of power are unexamined and remain unchanged. The field of deafness provides a powerful example of the way in which competing interests can be played out under the guise of choice of communication methods. Historically, teachers of the deaf have been divided about whether deaf children should be educated through speech or sign. However, recognition of the legitimacy of native sign languages has caused a shift in the debate to the linguistic basis of this communication and the way in which language policy privileges one cultural group and its method of communication over another.

Allegations of unlawful discrimination in education: parents taking their fight for Auslan to the courts

This paper examines the use of the Disability Discrimination Act (Commonwealth of Australia, 1992) by parents seeking access for their deaf children to native sign language in the classroom. It reviews a number of cases in which Australian parents have claimed indirect discrimination by educational authorities over their children's lack of access to instruction through Australian Sign Language (Auslan) and discusses the outcomes of such litigation. The policies endorsed by deafness organizations are contrasted with those of state educational authorities. The author discusses the limitations of a complaints-based system to address systemic discrimination and suggests the need for legislation to protect the linguistic rights of deaf children.

HIV, stigma, and rates of infections : a rumour without evidence

The modern concept of a social stigma comes from the work of American sociologist Erving Goffman, who described it as a response to a deeply discrediting attribute that devalues the person [1]. In the medical literature, stigma is almost inevitably written about in terms of adverse social sequelae of a disease—such as leprosy, tuberculosis, epilepsy, schizophrenia, or filariasis [2–6]—or a physical characteristic or functional loss, such as obesity, deafness, or paraplegia [7–9]. The consequences of stigma range from moderate opprobrium at one end of the spectrum to death [10].

Applying social critical literacy theory to deaf education

This article explores social critical literacy theory and its application to deaf education. It argues that critical literacy offers an approach that can lead to engagement with and empowerment over written text, repositioning students as researchers of language. Texts that represent deaf people - if only through their absence - offer an opportunity for deaf students to engage in literate practices in meaningful contexts. An example of critical text analysis is provided using articles on a contested issue: cochlear implantation.

The mathematical and science skills of students who are deaf or hard of hearing educated in inclusive settings

This study examined the science and mathematics achievements of 16 Year 9 students with hearing loss in an inclusive high-school setting in Western Australia. Results from the Monitoring Standards in Education (MSE) compulsory state tests were compared with state and class averages for students with normal hearing. Data were collected from three cohorts of Year 9 students across a 3-year period (2005‐2007). Results from mathematics MSE9 and the MSE9 science assessments showed that the majority of students with hearing loss performed below the state average (88%). Findings in this study suggest that students with hearing loss demonstrated more mathematical strength in the areas of space and measurement, which use visuo-spatial skills. Results for students with hearing loss in the five sections of the science assessment suggest more consistency across the different areas tested in the MSE. Comparisons with the MSE9 English paper for the 2005 cohort of students with hearing loss suggest a strong relationship between reading and writing skills and performance on mathematics and science assessment. In particular, questions with high language content created difficulty. On the science assessment, questions requiring a written explanation appeared to be particularly challenging. These findings have implications for teaching and learning in these crucial areas for students with hearing loss in inclusive secondary school settings. Greater attention to the interpretation of the language of mathematics and to writing about science concepts may help to improve outcomes for students with hearing loss on statewide assessments

Social and professional participation of individuals who are deaf : utilizing the psychosocial potential maximization framework

This article documents a strength-based understanding of how individuals who are deaf maximize their social and professional potential. This exploratory study was conducted with 49 adult participants who are deaf (n ¼ 30) and who have typical hearing (n ¼ 19) residing in America, Australia, England, and South Africa. The findings support a systematic and comprehensive framework of proactive psychosocial attributes and tactics. Statistical analysis showed no significant differences between the groups across four variables of psychosocial competencies. Qualitative data further suggests that participants who are deaf maximize their potential using two types of proactive psychosocial attributes and tactics: 1) skills that individuals with typical hearing use and 2) specialized skills for identifying, circumventing, or mastering deafness-related difficulties. These findings contribute to understandings of how individuals who are deaf can achieve social and professional success.

When William Wallace was a unionist

  James Russell Thompson was a successful businessman from Airdrie in Scotland. He arrived in the Victorian gold-mining town of Ballarat in 1853, having previously struck gold on the Ovens goldfields. Deafness caused by his earlier career in mining prevented Thompson from becoming involved in public life in Ballarat but, dying a wealthy man in May 1886, he was able to leave significant bequests to relatives and requested that his remaining estate be put towards the purchase of statues for Ballarat's sprawling botanic gardens. A fellow Scot, Thomas Stoddart, was executor of Thompson's estate, and was able to procure for the gardens numerous monuments and statues made of Italian Carrara marble. The most notable of Stoddart's procurements was the statue of the Scottish hero William Wallace. The Ballarat Star noted that "the statue of Wallace was decided on as a compliment to Mr Thompson's love for the country he came from-an effigy of the greatest character ... in Scottish history or legend". The statue of Wallace in Ballarat's botanic gardens was unveiled and bequeathed to the city on May 24, 1889. It is one of very few outside Scotland.