BACKGROUND: Hearing loss with enlarged vestibular aqueduct (EVA) can be inherited as an autosomal recessive trait caused by bi-allelic mutations of SLC26A4. However, many EVA patients have non-diagnostic SLC26A4 genotypes with only one or no detectable mutant alleles. METHODS AND RESULTS: In this study, the authors were unable to detect occult SLC26A4 mutations in EVA patients with non-diagnostic genotypes by custom comparative genomic hybridisation (CGH) microarray analysis or by sequence analysis of conserved non-coding regions. The authors sought to compare the segregation of EVA among 71 families with two (M2), one (M1) or no (M0) detectable mutant alleles of SLC26A4. The segregation ratios of EVA in the M1 and M2 groups were similar, but the segregation ratio for M1 was significantly higher than in the M0 group. Haplotype analyses of SLC26A4-linked STR markers in M0 and M1 families revealed discordant segregation of EVA with these markers in eight of 24 M0 families. CONCLUSION: The results support the hypothesis of a second, undetected SLC26A4 mutation that accounts for EVA in the M1 patients, in contrast to non-genetic factors, complex inheritance, or aetiologic heterogeneity in the M0 group of patients. These results will be helpful for counselling EVA families with non-diagnostic SLC26A4 genotypes.
BACKGROUND:Hearing loss with enlarged vestibular aqueduct (EVA) can be inherited as an autosomal recessive trait caused by bi-allelic mutations of SLC26A4. However, many EVA patients have non-diagnostic SLC26A4 genotypes with only one or no detectable mutant alleles. METHODS AND RESULTS: In this study, the authors were unable to detect occult SLC26A4 mutations in EVA patients with non-diagnostic genotypes by custom comparative genomic hybridisation (CGH) microarray analysis or by sequence analysis of conserved non-coding regions. The authors sought to compare the segregation of EVA among 71 families with two (M2), one (M1) or no (M0) detectable mutant alleles of SLC26A4. The segregation ratios of EVA in the M1 and M2 groups were similar, but the segregation ratio for M1 was significantly higher than in the M0 group. Haplotype analyses of SLC26A4-linked STR markers in M0 and M1 families revealed discordant segregation of EVA with these markers in eight of 24 M0 families. CONCLUSION: The results support the hypothesis of a second, undetected SLC26A4 mutation that accounts for EVA in the M1 patients, in contrast to non-genetic factors, complex inheritance, or aetiologic heterogeneity in the M0 group of patients. These results will be helpful for counselling EVA families with non-diagnostic SLC26A4 genotypes.
Authors: Shannon P Pryor; Gail J Demmler; Anne C Madeo; Yandan Yang; Chris K Zalewski; Carmen C Brewer; John A Butman; Karen B Fowler; Andrew J Griffith Journal: Arch Otolaryngol Head Neck Surg Date: 2005-05
Authors: P D Phelps; R A Coffey; R C Trembath; L M Luxon; A B Grossman; K E Britton; P Kendall-Taylor; J M Graham; B C Cadge; S G Stephens; M E Pembrey; W Reardon Journal: Clin Radiol Date: 1998-04 Impact factor: 2.350
Authors: S P Pryor; A C Madeo; J C Reynolds; N J Sarlis; K S Arnos; W E Nance; Y Yang; C K Zalewski; C C Brewer; J A Butman; A J Griffith Journal: J Med Genet Date: 2005-02 Impact factor: 6.318
Authors: L A Everett; B Glaser; J C Beck; J R Idol; A Buchs; M Heyman; F Adawi; E Hazani; E Nassir; A D Baxevanis; V C Sheffield; E D Green Journal: Nat Genet Date: 1997-12 Impact factor: 38.330
Authors: B Coyle; W Reardon; J A Herbrick; L C Tsui; E Gausden; J Lee; R Coffey; A Grueters; A Grossman4; P D Phelps; L Luxon; P Kendall-Taylor; S W Scherer; R C Trembath Journal: Hum Mol Genet Date: 1998-07 Impact factor: 6.150
Authors: Julie A Muskett; Parna Chattaraj; John F Heneghan; Fabian R Reimold; Boris E Shmukler; Carmen C Brewer; Kelly A King; Christopher K Zalewski; Thomas H Shawker; John A Butman; Margaret A Kenna; Wade W Chien; Seth L Alper; Andrew J Griffith Journal: Laryngoscope Date: 2015-10-20 Impact factor: 3.325
Authors: Jane Rose; Julie A Muskett; Kelly A King; Christopher K Zalewski; Parna Chattaraj; John A Butman; Margaret A Kenna; Wade W Chien; Carmen C Brewer; Andrew J Griffith Journal: Laryngoscope Date: 2016-11-15 Impact factor: 3.325
Authors: Parna Chattaraj; Tina Munjal; Keiji Honda; Nanna D Rendtorff; Jessica S Ratay; Julie A Muskett; Davide S Risso; Isabelle Roux; E Michael Gertz; Alejandro A Schäffer; Thomas B Friedman; Robert J Morell; Lisbeth Tranebjærg; Andrew J Griffith Journal: J Med Genet Date: 2017-08-05 Impact factor: 6.318
Authors: Taku Ito; Byung Yoon Choi; Kelly A King; Christopher K Zalewski; Julie Muskett; Parna Chattaraj; Thomas Shawker; James C Reynolds; John A Butman; Carmen C Brewer; Philine Wangemann; Seth L Alper; Andrew J Griffith Journal: Cell Physiol Biochem Date: 2011-11-18
Authors: Andrea M Oza; Marina T DiStefano; Sarah E Hemphill; Brandon J Cushman; Andrew R Grant; Rebecca K Siegert; Jun Shen; Alex Chapin; Nicole J Boczek; Lisa A Schimmenti; Jaclyn B Murry; Linda Hasadsri; Kiyomitsu Nara; Margaret Kenna; Kevin T Booth; Hela Azaiez; Andrew Griffith; Karen B Avraham; Hannie Kremer; Heidi L Rehm; Sami S Amr; Ahmad N Abou Tayoun Journal: Hum Mutat Date: 2018-11 Impact factor: 4.878
Authors: Taku Ito; Julie Muskett; Parna Chattaraj; Byung Yoon Choi; Kyu Yup Lee; Christopher K Zalewski; Kelly A King; Xiangming Li; Philine Wangemann; Thomas Shawker; Carmen C Brewer; Seth L Alper; Andrew J Griffith Journal: World J Otorhinolaryngol Date: 2013-05-28