Coucke et al. (1994) reported a large Indonesian family with autosomal dominant nonsyndromic progressive sensorineural hearing loss. The hearing loss first affected the high frequencies during the teens or 20s and became profound within 10 years.
... Coucke et al. (1994) reported a large Indonesian family with autosomal dominant nonsyndromic progressive sensorineural hearing loss. The hearing loss first affected the high frequencies during the teens or 20s and became profound within 10 years. Van Camp et al. (1997) reported 3 families with autosomal dominant hearing loss from Belgium and the Netherlands. The families showed a similar progressive sensorineural hearing loss, starting in the high frequencies and also affecting the middle and low frequencies later in life. Marres et al. (1997) examined 43 presumably affected persons in a 6-generation Dutch family with autosomal dominant hearing loss and linkage to chromosome 1p. Regression analysis showed significant and equal linear progression in the disorder with age (by about 1 decibel per year) at all frequencies. In 25 to 35% of the patients, an increased vestibuloocular reflex as measured by rotatory responses was observed. Kubisch et al. (1999) reported a French family with autosomal dominant progressive deafness. In the first generation, deafness was detected in early childhood, in the second generation around puberty, and in the third generation in early childhood. The third generation individual complained about tinnitus since the age of 3 years. In all 3 affected individuals, the hearing loss was more severe on high frequencies, with hearing loss between 50 and 90 dB at 500 Hz and between 90 and 120 dB at 2 and 4 kHz. There was no evidence of vestibular involvement.
Kubisch et. al (1999) cloned the voltage-gated potassium channel KCNQ4 gene and identified a heterozygous mutation (G285S; 603537.0001) in affected members of a pedigree with DFNA2A.
In affected members of 2 Dutch families, an American family, ... Kubisch et. al (1999) cloned the voltage-gated potassium channel KCNQ4 gene and identified a heterozygous mutation (G285S; 603537.0001) in affected members of a pedigree with DFNA2A. In affected members of 2 Dutch families, an American family, and a Belgian family with DFNA2A, Coucke et al. (1999) identified 4 different heterozygous mutations in the KCNQ4 gene (603537.0002-603537.0005). In affected members of a Japanese family with DFNA2A, Kamada et al. (2006) identified a heterozygous 1-bp deletion (603537.0008) in the KCNQ4 gene, resulting in a truncated protein without transmembrane domains. Affected individuals had late-onset (8 to 50 years) pure high frequency hearing loss, which was less severe compared to previously reported patients with missense mutations in the KCNQ4 gene. Kamada et al. (2006) postulated different pathogenic mechanisms to explain the phenotypic differences: haploinsufficiency in deletion mutations and dominant-negative effects in missense mutations. In affected members of a 4-generation Spanish family with postlingual, bilateral, symmetric, and progressive sensorineural hearing impairment at mid and high frequencies, Mencia et al. (2008) identified a heterozygous mutation in the KCNQ4 gene (G296S; 603537.0009). The earliest clinical evidence of hearing loss in the family was at 5 years of age. Affected individuals did not exhibit tinnitus or clinical features suggestive of vestibular dysfunction.