The genetics of diabetes mellitus

Genes play an important role in the development of diabetes mellitus. Putative susceptibility genes could be the key to the development of diabetes. Type 1 diabetes mellitus is one of the most common chronic diseases of childhood. A combination of genetic and environmental factors is most likely the cause of Type 1 diabetes. The pathogenetic sequence leading to the selective autoimmune destruction of islet beta-cells and development of Type 1 diabetes involves genetic factors, environmental factors, immune regulation and chemical mediators. Unlike Type 1 diabetes mellitus, Type 2 diabetes is often considered a polygenic disorder with multiple genes located on different chromosomes being associated with this condition. This is further complicated by numerous environmental factors which also contribute to the clinical manifestation of the disorder in genetically predisposed persons. Only a minority of cases of type 2 diabetes are caused by single gene defects such as maturity onset diabetes of the young (MODY), syndrome of insulin resistance (insulin receptor defect) and maternally inherited diabetes and deafness (mitochondrial gene defect). Although Type 2 diabetes mellitus appears in almost epidemic proportions our knowledge of the mechanism of this disease is limited. More information about insulin secretion and action and the genetic variability of the various factors involved will contribute to better understanding and classification of this group of diseases. This article discusses the results of various genetic studies on diabetes with special reference to Indian population.

Opportunistic assessment of hearing in elderly inpatients

Objective: To determine the prevalence of occult hearing loss in elderly inpatients, to evaluate feasibility of opportunistic hearing screening and to determine subsequent provision of hearing aids. Materials and methods: Subjects (>65 years) were recruited from five elderly care wards. Hearing loss was detected by a ward-based hearing screen comprising patient-reported assessment of hearing disability and a whisper test. Subjects failing the whisper test or reporting hearing difficulties were offered formal audiological assessment. Results: Screening was performed on 51 patients aged between 70 and 95 years. Of the patients, 21 (41%) reported hearing loss and 16 (31%) failed the whisper test. A total of 37 patients (73%) were referred for audiological assessment with 17 (33%) found to have aidable hearing loss and 11 were fitted with hearing aids (22%). Discussion: This study highlights the high prevalence of occult hearing loss in elderly inpatients. Easy two-step screening can accurately identify patients with undiagnosed deafness resulting in significant proportions receiving hearing aids.

Rethinking disability theory and practice: challenging essentialism

This edited volume argues that even in recent Critical Disability Studies which have sought to critique essentialist assumptions in relation to Disability, nevertheless essentialisms remain which predetermine and predirect definitions and arguments in the field. This volume analyses such essentialisms in a wide range of areas such as childhood, gender, sexuality, reproduction, ADHD, autism, the animal, d/Deafness, hirsutism, the body, and vision. Particularly issues such as 'agency', 'voice' and 'body' are explored in terms of their political implications.

An analysis of teaching methods for children who are deaf with multiple disabilities

This study analyzes the placement, services, and teaching methods of students who are deaf with additional disabilities. Through this analysis, these students are compared to students with multiple disabilities, not including deafness.

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

Escuta clínica e atitude fenomenológica no atendimento à pessoa surda: reflexões sobre um processo psicoterápico

Psychology uses listening as a work resource. When it comes to psychotherapy, listening establishes communication and makes psychologist-client dialogue easier. This qualitative research aims to discuss the clinic listening in phenomenological attitude in existential-phenomenological psychotherapy with deaf people. This perspective is based on the thinking of German philosopher Martin Heidegger, who considers humane a being-with and being-in-the-world, always unveiling meanings. Regarding the deaf people, Libras is currently the natural language of Brazilian deaf people. In this new language configuration, communication occurs in a visual-spatial modality. Thus, listening and speech gain new dimensions, demanding different ways of understanding in the field of psychotherapy. To the development of this research, we present excerpts from therapeutic sessions narratives with a deaf client, interpreted in the light of Heidegger s hermeneutics. We consider that it is possible for the psychotherapist to listen to deaf people in phenomenological attitude. Such position, which does not naturalize and limit the humane, helps so that the clients do not feel responsible for their existence and can hermeneutically converse in their language. In this context, the psychologist must be qualified to conduct the treatment in Libras. We hope that this research can, somehow, fill the existing gap of the scientific production about such theme in the field of Psychology and, mainly, instigate discussion in the context of Psychology courses on the importance and need to qualify psychologists for the management of clinical practice with deaf people

Análise da produção científica nacional fonoaudiológica acerca da linguagem escrita

TEMA: a produção científica nacional sobre a linguagem escrita no âmbito da Fonoaudiologia. OBJETIVO: analisar parte da produção fonoaudiológica brasileira acerca da linguagem escrita, entre os anos de 1980 a 2004, levando em conta o período da publicação; a distribuição de freqüência por período; os tipos de publicações; as sub-temáticas abordadas e a autoria. MÉTODO: a pesquisa de caráter documental configurou a opção metodológica selecionada para a realização desse estudo. Foram analisados livros, capítulos de livros e artigos publicados em sete periódicos nacionais de Fonoaudiologia (1980 a 2004). RESULTADOS: as produções científicas em torno da linguagem escrita, no período considerado, perfazem um total de 236 publicações. Desse total, 3,39% foram publicadas na década de 1980; 44,1% na década de 1990; e 52,5% durante o período de 2000-2004. Quanto ao tipo das publicações, 18,5% foram publicadas em forma de livro, 39% de capítulo de livro e 42,5% de artigo em periódico. Quanto à autoria das publicações, 42 autores (76,36%), são vinculados a instituições de ensino superior, como docentes ou discentes, com maior concentração no Estado de São Paulo e menor no Rio de Janeiro. As produções analisadas versaram sobre cinco sub-temáticas: distúrbios de linguagem escrita (52%); processo de apropriação da linguagem escrita (23,5%); surdez e linguagem escrita (8,90%); alterações neurológicas e linguagem escrita (8,22%) e escola e linguagem escrita (7,53%). CONCLUSÃO: a pesquisa permitiu recuperar parte da memória acerca da construção de um campo de atuação e de conhecimento da área fonoaudiológica: a linguagem escrita. O ascendente crescimento de publicações em torno dessa temática aponta para o implemento de pesquisas nesse campo da Fonoaudiologia e, portanto, a pertinência de estudos que objetivem analisar os rumos da produção científica relativa ao mesmo.

Potencial evocado auditivo para diagnóstico de surdez bilateral em dois cães

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)