Lalwani et al. (1999) studied a 5-generation American family, previously reported by Lalwani et al. (1997), with deafness caused by cochleosaccular degeneration (CSD). CSD is the most common histopathologic finding in cases of profound congenital deafness and is ... Lalwani et al. (1999) studied a 5-generation American family, previously reported by Lalwani et al. (1997), with deafness caused by cochleosaccular degeneration (CSD). CSD is the most common histopathologic finding in cases of profound congenital deafness and is estimated to occur in approximately 70% of cases. CSD was first described by Scheibe (1892) and is commonly known as Scheibe dysplasia. It affects structures that are derived from the pars inferior of the otocyst. Thus, the membranous cochlea and saccule are affected, but the osseous labyrinth, the membranous utricle, and the semicircular canals are normal. The family studied by Lalwani et al. (1997, 1999) had been identified through a temporal bone database; because there is no clinically available test to diagnose CSD, postmortem histologic examination of the temporal bone is required. The affected family members exhibited nonsyndromic hearing loss with an autosomal dominant mode of transmission; there was no pigmentary abnormality. The hearing impairment began at age 10 years and involved only the high frequencies; by the third decade of life, affected family members had moderate to severe deafness. Hildebrand et al. (2006) reported a 5-generation Australian family of Anglo Celtic origin with nonsyndromic DFNA17. The self-reported age of onset ranged from 6 years to the mid-twenties. The hearing loss was progressive with a general trend of initial mild high-frequency loss during childhood and adolescence and with a flattening of the audiogram over time. The hearing loss became severe to profound by the second to third decades, although there was some intrafamilial variability.
DFNA17 maps to the same region as MYH9 (160775), a nonmuscle-myosin heavy-chain gene. Because of the importance of myosins in hearing, Lalwani et al. (2000) tested MYH9 as a candidate gene for DFNA17. Expression of MYH9 in the ... DFNA17 maps to the same region as MYH9 (160775), a nonmuscle-myosin heavy-chain gene. Because of the importance of myosins in hearing, Lalwani et al. (2000) tested MYH9 as a candidate gene for DFNA17. Expression of MYH9 in the rat cochlea was confirmed using RT-PCR and immunohistochemistry analysis. MYH9 was immunolocalized in the organ of Corti, the subcentral region of the spiral ligament, and the Reissner membrane. Sequence analysis of MYH9 in the family previously studied by Lalwani et al. (1997, 1999) demonstrated that a heterozygous mutation (R705H; 160775.0008) cosegregated with deafness. In affected members of a 5-generation Australian family of Anglo Celtic origin with nonsyndromic DFNA17, Hildebrand et al. (2006) identified a heterozygous R705H mutation in the MYH9 gene.