Autosomal dominant deafness-41 (DFNA41) is characterized by onset of progressive sensorineural hearing loss usually in the second decade. The hearing loss is severe and ultimately affects all frequencies. Exposure to noise exacerbates the hearing loss, particularly at high frequencies ...Autosomal dominant deafness-41 (DFNA41) is characterized by onset of progressive sensorineural hearing loss usually in the second decade. The hearing loss is severe and ultimately affects all frequencies. Exposure to noise exacerbates the hearing loss, particularly at high frequencies (summary by Yan et al., 2013)
Blanton et al. (2002) reported a large Chinese family in which 30 members over 6 generations had nonsyndromic progressive sensorineural deafness involving all frequencies. The age at onset ranged from 12 to 20 years and was generally accompanied by ...Blanton et al. (2002) reported a large Chinese family in which 30 members over 6 generations had nonsyndromic progressive sensorineural deafness involving all frequencies. The age at onset ranged from 12 to 20 years and was generally accompanied by high frequency tinnitus. Yan et al. (2005) provided follow-up of the family reported by Blanton et al. (2002) and reported an additional Chinese family with the same disorder. All had moderate to severe progressive sensorineural hearing loss with onset in the second decade with severe loss by age 20 years. Some patients in the second family showed increased thresholds at age 6 to 10 years, suggesting an even earlier onset. Those with occupational noise exposure early in life had more severe hearing loss at high frequencies compared to those without noise exposure. Imaging of the temporal bone in 1 patient showed no abnormalities. Faletra et al. (2013) reported a large Italian family with onset of progressive sensorineural hearing loss in the second decade. The hearing loss could be classified as mild to profound in almost all affected family members, mainly affecting medium to high frequencies (1,000 and 4,000 Hz). The severity of the disorder appeared to worsen with age. Imaging of the temporal bone showed no abnormalities
In affected members of 2 unrelated Chinese families with autosomal dominant deafness-41, Yan et al. (2013) identified a heterozygous missense mutation in the P2RX2 gene (V60L; 600844.0001). The mutation in the first family (Blanton et al., 2002) was found ...In affected members of 2 unrelated Chinese families with autosomal dominant deafness-41, Yan et al. (2013) identified a heterozygous missense mutation in the P2RX2 gene (V60L; 600844.0001). The mutation in the first family (Blanton et al., 2002) was found by whole-exome sequencing; the second family was 1 of 65 families in whom the P2RX2 gene was sequenced. In vitro functional expression studies showed that the V60L mutation caused a loss of channel function with a loss of inward current and macropore permeability. The findings provided a link between P2X2 receptor signaling in the cochlea and protection from noise and progressive hearing loss. Faletra et al. (2013) identified a heterozygous missense mutation in the P2RX2 gene (G353R; 600844.0002) in affected members of a large Italian family with DFNA41, confirming the findings of Yan et al. (2013) that mutations in this gene can cause progressive hearing loss