Chunyan Qu1, Fenghe Liang2, Qin Long3, Min Zhao1, Haiqiong Shang4, Lynn Fan5, Li Wang6, Joseph Foster7, Denise Yan8, Xuezhong Liu7,8,9. 1. China Rehabilitation and Research Center for Deaf Children, Beijing 100029, China. 2. Department of Otolaryngology-Head and Neck Surgery, Capital Medical University, Beijing Tongren Hospital, Beijing 100730, China. 3. Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China. 4. Department of Otolaryngology-Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China. 5. BSc, University of Miami, Miami, FL 33136, USA. 6. Institute of Medical Genetics, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou 450003, China. 7. Department of Human Genetics, John P. Hussman Institute for Human Genomics, University of Miami, FL 33136, USA. 8. Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL 33136, USA. 9. Dr. John T. Macdonald Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
Abstract
INTRODUCTION: Usher syndrome is the most common cause of hereditary deaf-blindness. Three clinical subtypes have been classified. Usher syndrome type I is the most severe subtype characterized by congenital severe-to-profound hearing loss, retinitis pigmentosa and vestibular dysfunction. METHODS: One family was analyzed and the analysis included the combination of a custom capture/next-generation sequencing panel of 180 known deafness gene, Sanger sequencing and bioinformatics approaches. RESULTS: Compound heterozygous mutations in the MYO7A gene: a known missense mutation c.494C>T (p.Thr165Met) and a novel missense mutation c.6113G>A (p.Gly2038Glu) were identified in a proband. This Chinese hearing-impaired child was misdiagnosed as non-syndromic hearing loss which was later changed to the diagnosis of Usher syndrome type I after comprehensive audiometric, vestibular and ophthalmological examinations at 9 years old. CONCLUSIONS: Due to the features of genetic heterogeneity and variation in clinical manifestation, molecular diagnosis and ophthalmological examinations by skilled ophthalmologists with knowledge of Usher syndrome should be suggested as a routine assessment which may improve the accuracy and reliability of etiological diagnosis for hearing loss.
INTRODUCTION: Usher syndrome is the most common cause of hereditary deaf-blindness. Three clinical subtypes have been classified. Usher syndrome type I is the most severe subtype characterized by congenital severe-to-profound hearing loss, retinitis pigmentosa and vestibular dysfunction. METHODS: One family was analyzed and the analysis included the combination of a custom capture/next-generation sequencing panel of 180 known deafness gene, Sanger sequencing and bioinformatics approaches. RESULTS: Compound heterozygous mutations in the MYO7A gene: a known missense mutation c.494C>T (p.Thr165Met) and a novel missense mutation c.6113G>A (p.Gly2038Glu) were identified in a proband. This Chinese hearing-impaired child was misdiagnosed as non-syndromic hearing loss which was later changed to the diagnosis of Usher syndrome type I after comprehensive audiometric, vestibular and ophthalmological examinations at 9 years old. CONCLUSIONS: Due to the features of genetic heterogeneity and variation in clinical manifestation, molecular diagnosis and ophthalmological examinations by skilled ophthalmologists with knowledge of Usher syndrome should be suggested as a routine assessment which may improve the accuracy and reliability of etiological diagnosis for hearing loss.
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