OBJECTIVE: To delineate the phenotype and genotype of an autosomal dominant low-frequency sensorineural nonsyndromic hearing impairment trait in relation to similar traits. STUDY DESIGN: Family study, including retrospective case reviews. SETTING: Tertiary referral center. PATIENTS: Hearing impairment was documented in 11 family members in five generations, 8 of whom were alive and participated in this study. INTERVENTION: Diagnostic. MAIN OUTCOME MEASURES: Clinical study: medical and otologic history and examination, retrieval of previous audiograms, pure-tone audiometry, and statistical analysis of audiometric data. Genetic study: linkage analysis of blood samples in 18 clinically affected and nonaffected family members. RESULTS: Hearing impairment had been present since early childhood, mainly affecting the low frequencies (mean threshold 45 dB HL at 0.25-1 kHz); speech recognition was hardly affected during the first three decades of life. Higher frequencies became involved with increasing age, thus causing a flat-type audiogram at middle age and down-sloping audiograms after age 60 years. Progression was mild but significant at all frequencies (0.5 dB/year at 0.25 kHz to 1.3 dB/year at 8 kHz) and persisted after correction was applied for normal presbyacusis. The trait was linked to chromosome 4p16.3, in a region comprising both the previously located, closely adjacent DFNA6 and the DFNA14 loci for low-frequency hearing impairment. CONCLUSION: A third family (designated Dutch II) was identified with a low-frequency hearing impairment trait showing linkage to chromosome 4p16.3 (DFNA6/14). The progression of hearing impairment beyond presbyacusis in the current study is unprecedented for DFNA6/14 traits.
OBJECTIVE: To delineate the phenotype and genotype of an autosomal dominant low-frequency sensorineural nonsyndromic hearing impairment trait in relation to similar traits. STUDY DESIGN: Family study, including retrospective case reviews. SETTING: Tertiary referral center. PATIENTS: Hearing impairment was documented in 11 family members in five generations, 8 of whom were alive and participated in this study. INTERVENTION: Diagnostic. MAIN OUTCOME MEASURES: Clinical study: medical and otologic history and examination, retrieval of previous audiograms, pure-tone audiometry, and statistical analysis of audiometric data. Genetic study: linkage analysis of blood samples in 18 clinically affected and nonaffected family members. RESULTS:Hearing impairment had been present since early childhood, mainly affecting the low frequencies (mean threshold 45 dB HL at 0.25-1 kHz); speech recognition was hardly affected during the first three decades of life. Higher frequencies became involved with increasing age, thus causing a flat-type audiogram at middle age and down-sloping audiograms after age 60 years. Progression was mild but significant at all frequencies (0.5 dB/year at 0.25 kHz to 1.3 dB/year at 8 kHz) and persisted after correction was applied for normal presbyacusis. The trait was linked to chromosome 4p16.3, in a region comprising both the previously located, closely adjacent DFNA6 and the DFNA14 loci for low-frequency hearing impairment. CONCLUSION: A third family (designated Dutch II) was identified with a low-frequency hearing impairment trait showing linkage to chromosome 4p16.3 (DFNA6/14). The progression of hearing impairment beyond presbyacusis in the current study is unprecedented for DFNA6/14 traits.
Authors: Kyle R Taylor; Kevin T Booth; Hela Azaiez; Christina M Sloan; Diana L Kolbe; Emily N Glanz; A Eliot Shearer; Adam P DeLuca; V Nikhil Anand; Michael S Hildebrand; Allen C Simpson; Robert W Eppsteiner; Todd E Scheetz; Terry A Braun; Patrick L M Huygen; Richard J H Smith; Thomas L Casavant Journal: Ann Otol Rhinol Laryngol Date: 2015-11-03 Impact factor: 1.547