Jain et al. (1997, 1998) reported a large consanguineous Indian family in which several members had profound, prelingual, nonsyndromic sensorineural deafness. Vestibular function and visual function were normal.
Verpy et al. (2000) identified a PDZ-domain-containing gene on 11p15.1-p14, mutations in which are responsible for USH1C. They proposed that the USH1C gene underlies the DFNB18 form of isolated deafness also. They suggested that the fact that several ... Verpy et al. (2000) identified a PDZ-domain-containing gene on 11p15.1-p14, mutations in which are responsible for USH1C. They proposed that the USH1C gene underlies the DFNB18 form of isolated deafness also. They suggested that the fact that several of the inner ear Ush1c transcripts of the mouse are not present in the eye is consistent with mutations in the USH1C gene underlying a form of isolated deafness. Mutations in connexin-26 (121011) provide another example of syndrome deafness and nonsyndromic deafness being caused by different alleles of the same gene: isolated autosomal recessive deafness (220290), autosomal dominant isolated deafness (601544), and keratoderma with deafness (148350). In the family in which Jain et al. (1998) mapped DFNB18 to 11p, Ahmed et al. (2002) identified a leaky splice site mutation in the harmonin gene (605242.0008), indicating that Usher syndrome type IC and DFNB18 are allelic. Ouyang et al. (2002) indeed demonstrated that mutations in alternatively spliced exons of USH1C cause nonsyndromic recessive deafness DFNB18. They screened 32 Chinese multiplex families with nonsyndromic recessive deafness for USH1C mutations. In 1 family, congenital profound deafness without RP was associated with a C-to-G transversion in the alternatively spliced exon D, predicting an arg608-to-pro (605242.0009) amino acid substitution in the proline-, serine-, and threonine-rich region of harmonin. They also screened 320 deaf probands from other ethnic backgrounds and found 3 who were heterozygous for changes in the alternately spliced exons. None of these mutations were detected in DNA from 200 control subjects with normal hearing, including 110 Chinese. These findings showed that USH1C mutations can also cause nonsyndromic deafness and that some harmonin isoforms are specifically required for inner ear function.