Deafness, Autosomal Recessive 29

A number sign (#) is used with this entry because of evidence that autosomal recessive nonsyndromic deafness-29 (DFNB29) is caused by homozygous mutation in the CLDN14 gene (605608) on chromosome 21q22.

Clinical Features

Wilcox et al. (2001) described 2 large consanguineous Pakistani families segregating profound congenital deafness.

Lee et al. (2012) reported 4 consanguineous Pakistani families in which multiple members had prelingual onset of nonsyndromic, nonprogressive severe to profound hearing loss affecting all frequencies, with greater loss in the high frequencies. The audiograms showed a downward slope.

Mapping

In 2 Pakistani families segregating autosomal recessive nonsyndromic deafness, Wilcox et al. (2001) found maximum 2-point lod scores of 6.7 at theta of zero for marker D21S1252 and 6.1 at theta of zero for marker D21S2079, respectively. Critical recombinants and homozygosity for polymorphic markers defined a linkage interval of 228,600 bp on 21q22.1. The authors designated the locus DFNB29.

Molecular Genetics

Wilcox et al. (2001) screened the candidate gene CLDN14 for mutations in 2 Pakistani families with DFNB29. They identified 2 homozygous mutations: a 1-bp deletion (398delT; 605608.0001) in 1 family and a missense mutation (V85D; 605608.0002) in the other.

In affected members of 4 consanguineous Pakistani families with DFNB29, Lee et al. (2012) identified 4 different homozygous mutations in the CLDN14 gene (605608.0002; 605608.0004-605608.0006). Functional studies of the variants were not performed. The families were ascertained from a larger cohort of 353 consanguineous Pakistani families with autosomal recessive nonsyndromic hearing loss who underwent linkage scans.