A human gene responsible for neurosensory, non-syndromic recessive deafness is a candidate homologue of the mouse sh-1 gene

Abstract

The identification of mouse models for the various forms of human neurosensory non-syndromic recessive deafness would constitute a major advance in the study of human deafness. Here we describe the localization of a human gene for neurosensory, nonsyndromic recessive deafness (NSRD2) to chromosome 11q13.5 by linkage analysis of a highly consanguineous family. A maximum lod score of 10.63 (theta = 0.018) was obtained for the microsatellite marker D11S527. Homozygosity mapping refined the localization of NSRD2 to a 6 cM interval also containing the olfactory marker protein (OMP) gene. The murine homologue of OMP is tightly linked to the autosomal recessive deafness gene sh-1. These results, and clinical data, suggest that NSRD2 is the human homologue of the mouse sh-1 gene.

A sensorineural progressive autosomal recessive form of isolated deafness, DFNB13, maps to chromosome 7q34-q36

“…23,24 These two studies also proved correct the hypotheses, based on linkage results, that (i) the same gene can be responsible for both a recessive (DFNB1) and a dominant (DFNA3) form of deafness 25 and that (ii) the same gene can be responsible for an isolated (DFNB2) and a syndromic (USH1B) form of deafness. 4,26 Since the autosomal dominant form of deafness, DFNA11, has been assigned to the same chromosomal region as DFNB2 and USH1B, 27 MYO7A is also likely to underly this dominant form of isolated deafness. Based on these considerations, we searched for a dominant form of isolated deafness or a syndromic form of deafness reportedly assigned to the same chromosomal region as DFNB13.…”

“…In such families, the probability of having more than one deafness gene segregating is minimised. Using this approach, we were able to localise the first two genes involved in autosomal recessive deafness, DFNB1 3 and DFNB2, 4 segregating in large families living in northern and southern Tunisia, respectively. Once linkage to a particular chromosomal region has been detected by linkage analysis, the localisation interval can be refined by the characterisation of homozygous regions present in affected individuals.…”

Estudo genético-clínico de 144 pacientes portadores de deficiência auditiva não sindrômica".

“…Podem ser congênitas, com perda unilateral ou bilateral leve e, freqüentemente, progressiva e de início pós-lingüístico (Guilford et al, 1994). Muitas famílias com perda auditiva não sindrômica…”

“…Segundo Guilford et al (1994) e Claros et al (1996), devido ao fato de iniciar-se no período pré-lingüístico e, geralmente, de grau profundo, a deficiência auditiva recessiva tende a ser mais grave do que a deficiência auditiva dominante. Liu e Xu (1994), em uma análise de audiogramas de indivíduos com deficiência auditiva não sindrômica, citam dois tipos de curvas no grupo autossômico recessivo -curva residual e curva com inclinação abrupta.…”

“…Tabela 13: Freqüência dos tipos e graus da deficiência auditiva simétrica e assimétrica nos diferentes modelos de herança genética (o número correspondente aos tipos referemse ao número de pacientes e o número correspondente aos graus referem-se ao número de orelhas) Dados quanto ao tipo, grau, lateralidade, simetria da curva audiométrica e início da perda auditiva encontrados nos pacientes com deficiência auditiva deste grupo foram compatíveis com dados da literatura, embora na sua maioria, a perda auditiva seja progressiva (Guilford et al, 1994;van Laer et al, 1999).…”