OBJECTIVES: To characterize mitochondrial sequence variants present in a nationwide hereditary deafness DNA repository of samples from deaf subjects and to define the clinical presentation and audiometric characteristics of individuals with a mitochondrial sequence variant. STUDY DESIGN: Retrospective review of results for select mitochondrial mutations performed on DNA samples from subjects compiled from 1997 to 2009. SETTING: National hereditary deafness DNA repository. SUBJECTS AND METHODS: Available samples from subjects in the repository were screened to identify those with mitochondrial sequence variants. Clinical data on the nature of mutation, type and severity of the hearing loss, and sex, age at diagnosis, family history of hearing loss, and ethnicity were analyzed. RESULTS: Eighty-six patients were identified with mitochondrial mutations or 3.5% of the subjects studied. Among those with mitochondrial mutations, 21 (24.4%) had the m.7445A>G substitution, 18 (20.9%) had the m.1555A>G substitution, 18 (20.9%) had the m.961T>G substitution, and 29 (33.7%) had a m.961delT+C(n) complex deletion. The majority of patients had bilateral severe to profound hearing loss. Fifty-three (62%) patients were female, and a family history of hearing loss was documented in 66 (76.7%) patients. The deafness was recognized prior to 3 years of age in 26 patients. CONCLUSION: Mitochondrial deafness in this sample was associated with a variety of genetic mutations and a wide spectrum of clinical presentations. Because of increased aminoglycoside susceptibility associated with some forms of mitochondrial deafness, matrilineal relatives may be at risk in those cases, highlighting the importance of making an accurate diagnosis prior to exposure.
OBJECTIVES: To characterize mitochondrial sequence variants present in a nationwide hereditary deafness DNA repository of samples from deaf subjects and to define the clinical presentation and audiometric characteristics of individuals with a mitochondrial sequence variant. STUDY DESIGN: Retrospective review of results for select mitochondrial mutations performed on DNA samples from subjects compiled from 1997 to 2009. SETTING: National hereditary deafness DNA repository. SUBJECTS AND METHODS: Available samples from subjects in the repository were screened to identify those with mitochondrial sequence variants. Clinical data on the nature of mutation, type and severity of the hearing loss, and sex, age at diagnosis, family history of hearing loss, and ethnicity were analyzed. RESULTS: Eighty-six patients were identified with mitochondrial mutations or 3.5% of the subjects studied. Among those with mitochondrial mutations, 21 (24.4%) had the m.7445A>G substitution, 18 (20.9%) had the m.1555A>G substitution, 18 (20.9%) had the m.961T>G substitution, and 29 (33.7%) had a m.961delT+C(n) complex deletion. The majority of patients had bilateral severe to profound hearing loss. Fifty-three (62%) patients were female, and a family history of hearing loss was documented in 66 (76.7%) patients. The deafness was recognized prior to 3 years of age in 26 patients. CONCLUSION:Mitochondrial deafness in this sample was associated with a variety of genetic mutations and a wide spectrum of clinical presentations. Because of increased aminoglycoside susceptibility associated with some forms of mitochondrial deafness, matrilineal relatives may be at risk in those cases, highlighting the importance of making an accurate diagnosis prior to exposure.
Entities:
Keywords:
DNA mutations; aminoglycoside; deafness; matrilineal inheritance; mitochondria; nonsyndromic hearing loss
Authors: Likhitha Kolla; Michael C Kelly; Zoe F Mann; Alejandro Anaya-Rocha; Kathryn Ellis; Abigail Lemons; Adam T Palermo; Kathy S So; Joseph C Mays; Joshua Orvis; Joseph C Burns; Ronna Hertzano; Elizabeth C Driver; Matthew W Kelley Journal: Nat Commun Date: 2020-05-13 Impact factor: 14.919
Authors: Dong Woo Nam; Sang Soo Park; So Min Lee; Myung-Whan Suh; Moo Kyun Park; Jae-Jin Song; Byung Yoon Choi; Jun Ho Lee; Seung Ha Oh; Kyung Chul Moon; Yo Han Ahn; Hee Gyung Kang; Hae Il Cheong; Ji Hyun Kim; Sang-Yeon Lee Journal: Biomed Res Int Date: 2022-09-09 Impact factor: 3.246