Grillet et al. (2009) studied a 5-generation consanguineous Iranian family segregating autosomal recessive nonsyndromic hearing loss. Affected members had preserved low-frequency hearing and a trend toward mild to moderate mid-frequency (500 to 2,000 Hz) and high-frequency (greater than ... Grillet et al. (2009) studied a 5-generation consanguineous Iranian family segregating autosomal recessive nonsyndromic hearing loss. Affected members had preserved low-frequency hearing and a trend toward mild to moderate mid-frequency (500 to 2,000 Hz) and high-frequency (greater than 2,000 Hz) hearing loss during childhood and adolescence. The onset of hearing loss was self-reported to occur at 7 to 8 years of age and progressed to become moderate to severe at mid and high frequencies during adulthood, with flattening of the audiogram over time. All affected individuals reported age-appropriate developmental motor milestones for sitting and walking and remained free of tinnitus, balance disorders, or vertigo, consistent with normal vestibular function.
In a 5-generation consanguineous Iranian family with nonsyndromic hearing loss mapping to chromosome 18q12-q21, Grillet et al. (2009) sequenced the LOXHD1 gene and identified a homozygous mutation (R670X; 613072.0001) in all affected family members tested. Unaffected family member ... In a 5-generation consanguineous Iranian family with nonsyndromic hearing loss mapping to chromosome 18q12-q21, Grillet et al. (2009) sequenced the LOXHD1 gene and identified a homozygous mutation (R670X; 613072.0001) in all affected family members tested. Unaffected family member were heterozygous for the mutation, which was not found in 243 controls. In 5 affected children from an Ashkenazi Jewish family with severe to profound congenital nonprogressive nonsyndromic hearing loss mapping to chromosome 18q, in which linkage to the GJB2 (121011)/GJB6 (604418) genes had been excluded, Edvardson et al. (2011) identified homozygosity for a nonsense mutation in the LOXHD1 gene (R1572X; 613072.0002). Analysis of LOXHD1 in an additional 8 Ashkenazi probands and 3 probands of mixed Jewish ethnicity led to the identification of another Ashkenazi Jewish family in which 4 affected children were found to be homozygous for R1572X. Screening for the mutation in 719 anonymous Ashkenazi individuals revealed 4 heterozygotes, indicating a carrier rate of 1:180 Ashkenazi Jews.