OBJECTIVES: Determine the diagnostic yield of a shared genetic testing algorithm in adult and pediatric populations with sensorineural hearing loss (SNHL) and recommend effective testing strategies to evaluate for genetic causes of deafness in patients presenting with idiopathic sensorineural hearing loss. STUDY DESIGN: Hospital-based cohort study. SETTING: University of Miami outpatient otology clinics between 2001 and 2010. SUBJECTS: Two hundred twenty-one adult and 163 pediatric patients with nonsyndromic sensorineural hearing loss. METHODS: Peripheral blood samples were screened for mutations in GJB2 and GJB6 and mitochondrial DNA mutations 1555A>G, 7444G>A, and 3243A>G. Audiometric data and family history were also collected. RESULTS: GJB2/GJB6-related deafness was diagnosed in 23 of 163 pediatric patients (14%) compared with only 3 of 221 adults (1%). All adults had a family history of hearing loss, and 2 patients noted deafness onset at birth. Nineteen GJB2 mutations were identified with 35delG the most common mutation. The 35delG homozygous state was the most common pathogenic genotype (54%). Mitochondrial DNA (mtDNA) mutations were found in 6 adult probands (3%). No mtDNA mutations were found in pediatric patients. CONCLUSION: Testing for common GJB2/GJB6 mutations in pediatric patients has considerable value in establishing an etiologic diagnosis for SNHL. Similar testing in adults is of very low yield except perhaps in cases of early-onset SNHL or strong family history. Mitochondrial DNA testing should be considered in adults with idiopathic SNHL.
OBJECTIVES: Determine the diagnostic yield of a shared genetic testing algorithm in adult and pediatric populations with sensorineural hearing loss (SNHL) and recommend effective testing strategies to evaluate for genetic causes of deafness in patients presenting with idiopathic sensorineural hearing loss. STUDY DESIGN: Hospital-based cohort study. SETTING: University of Miami outpatient otology clinics between 2001 and 2010. SUBJECTS: Two hundred twenty-one adult and 163 pediatric patients with nonsyndromic sensorineural hearing loss. METHODS: Peripheral blood samples were screened for mutations in GJB2 and GJB6 and mitochondrial DNA mutations 1555A>G, 7444G>A, and 3243A>G. Audiometric data and family history were also collected. RESULTS:GJB2/GJB6-related deafness was diagnosed in 23 of 163 pediatric patients (14%) compared with only 3 of 221 adults (1%). All adults had a family history of hearing loss, and 2 patients noted deafness onset at birth. Nineteen GJB2 mutations were identified with 35delG the most common mutation. The 35delG homozygous state was the most common pathogenic genotype (54%). Mitochondrial DNA (mtDNA) mutations were found in 6 adult probands (3%). No mtDNA mutations were found in pediatric patients. CONCLUSION: Testing for common GJB2/GJB6 mutations in pediatric patients has considerable value in establishing an etiologic diagnosis for SNHL. Similar testing in adults is of very low yield except perhaps in cases of early-onset SNHL or strong family history. Mitochondrial DNA testing should be considered in adults with idiopathic SNHL.
Authors: S Usami; S Abe; J Akita; A Namba; H Shinkawa; M Ishii; S Iwasaki; T Hoshino; J Ito; K Doi; T Kubo; T Nakagawa; S Komiyama; T Tono; S Komune Journal: J Med Genet Date: 2000-01 Impact factor: 6.318
Authors: Diego A Preciado; Lynne H Y Lim; Aliza P Cohen; Colm Madden; David Myer; Chris Ngo; John K Bradshaw; Louise Lawson; Daniel I Choo; John H Greinwald Journal: Otolaryngol Head Neck Surg Date: 2004-12 Impact factor: 3.497
Authors: X Estivill; N Govea; E Barceló; C Badenas; E Romero; L Moral; R Scozzri; L D'Urbano; M Zeviani; A Torroni Journal: Am J Hum Genet Date: 1998-01 Impact factor: 11.025
Authors: M'hamed Grati; Denise Yan; Manmeet H Raval; Tom Walsh; Qi Ma; Imen Chakchouk; Abhiraami Kannan-Sundhari; Rahul Mittal; Saber Masmoudi; Susan H Blanton; Mustafa Tekin; Mary-Claire King; Christopher M Yengo; Xue Zhong Liu Journal: Hum Mutat Date: 2016-02-16 Impact factor: 4.878