Sensorineural hearing loss (SNHL) is the most prevalent genetic sensory defect in humans. It is estimated that globally one out of every one thousand children born have profound hearing loss. Of those cases with genetic etiology, approximately 70% are non-syndromic. In addition, 80% of the non-syndromic SNHL cases are recessively inherited (ARNSHL), also known as DFNB. To date, few dozens of genes and gene loci have been implicated in DFNB.
DFNB2 is a form of neurosensory deafness with variable vestibular dysfunction. The age of onset of DFNB2 is usually at birth, but may occur later in life.
Ammar-Khodja et al. (2009) applied a systematic approach, involving haplotyping and genotyping, to depict the molecular etiology of non-syndromic deafness in 50 families and 9 sporadic cases from Algeria. One family with non-syndromic deafness carried a novel unclassified variant of unknown pathogenic effect in the MYO7A gene implicated in DFNB2.
Guilford et al. (1994) reported a consanguineous family from southern Tunisia in which 22 individuals had autosomal recessive non-syndromic sensorineural deafness. All had profound deafness, and 4 also had vertigo. The age of onset of deafness was variable and reported to range from birth to age 16 years. Linkage analysis demonstrated a possible linkage to chromosome 11q13 (maximum lod score of 10.63 at marker D11S527). Homozygosity mapping refined the location of the locus to a 6-cM interval that also contained the olfactory marker protein gene (OMP). The murine homolog of OMP is tightly linked to the autosomal recessive deafness shaker-1 gene in mice, suggesting that the deafness in this Tunisian family is the human homolog of the mouse shaker-1 mutation.
Later, Weil et al. (1997) identified a homozygous mutation in the MYO7A gene in affected members of the Tunisian family reported by Guilford et al. (1994). Much later, Zina et al. (2001) reevaluated the family reported by Guilford et al. (1994) and Weil et al. (1997). Since the original reports, five patients had developed mild retinal degeneration in addition to the progressive deafness. Fundus examination of one patient showed spicule pigmentary changes consistent with retinal dystrophy. Another previously unaffected family member, homozygous for the mutation, had retinitis pigmentosa. Seven patients had abnormal vestibular function as assessed by caloric tests. Zina et al. (2001) concluded that some patients in this Tunisian family had features consistent with Usher syndrome type IB. The findings suggested that other factors must modulate the expression of the phenotype.