机构：[1]Department of Otolaryngology-Head and Neck Surgery, Institute of Otolaryngology,PLA General Hospital, Beijing, China[2]Molecular Otolaryngology and Renal Research Laboratories and the Department ofOtolaryngology-Head and Neck Surgery, University of Iowa, Iowa City, Iowa, USA[3]Department of Otolaryngology-Head & Neck Surgery, Stanford University School ofMedicine, Stanford, California, USA[4]Beijing Institute of Otorhinolaryngology, Beijing Tongren Hospital, Capital MedicalUniversity, Beijing, China研究所耳鼻咽喉科研究所首都医科大学附属北京同仁医院首都医科大学附属同仁医院[5]National Institute of Biological Sciences, Beijing, China[6]Department of Communicative Disorders & Sciences, Center for Hearing andDeafness, University at Buffalo, Buffalo, New York, USA[7]Department of Radiology, PLA General Hospital, Beijing, China[8]Department of Neurology, PLA General Hospital, Beijing, China[9]Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy ofSciences, Beijing, China[10]BGI-Shenzhen, Shenzhen, China[11]Unité de Génétique et Physiologie de l’Audition, Institut Pasteur, Collège deFrance, Paris, France
Auditory neuropathy spectrum disorder (ANSD) is a form of hearing loss in which auditory signal transmission from the inner ear to the auditory nerve and brain stem is distorted, giving rise to speech perception difficulties beyond that expected for the observed degree of hearing loss. For many cases of ANSD, the underlying molecular pathology and the site of lesion remain unclear. The X-linked form of the condition, AUNX1, has been mapped to Xq23-q27.3, although the causative gene has yet to be identified.
We performed whole-exome sequencing on DNA samples from the AUNX1 family and another small phenotypically similar but unrelated ANSD family.
We identified two missense mutations in AIFM1 in these families: c.1352G>A (p.R451Q) in the AUNX1 family and c.1030C>T (p.L344F) in the second ANSD family. Mutation screening in a large cohort of 3 additional unrelated families and 93 sporadic cases with ANSD identified 9 more missense mutations in AIFM1. Bioinformatics analysis and expression studies support this gene as being causative of ANSD.
Variants in AIFM1 gene are a common cause of familial and sporadic ANSD and provide insight into the expanded spectrum of AIFM1-associated diseases. The finding of cochlear nerve hypoplasia in some patients was AIFM1-related ANSD implies that MRI may be of value in localising the site of lesion and suggests that cochlea implantation in these patients may have limited success.
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基金：
the National Key Basic Research
Program of China (no. 2014CB943001) and the National Natural Science
Foundation of China, Major Project (no. 81120108009) to QW; and the National
Institutes of Health (NIDCD DC003544, DC002842 and DC012049 to RJHS).
第一作者机构：[1]Department of Otolaryngology-Head and Neck Surgery, Institute of Otolaryngology,PLA General Hospital, Beijing, China
共同第一作者：
通讯作者：
通讯机构：[1]Department of Otolaryngology-Head and Neck Surgery, Institute of Otolaryngology,PLA General Hospital, Beijing, China[2]Molecular Otolaryngology and Renal Research Laboratories and the Department ofOtolaryngology-Head and Neck Surgery, University of Iowa, Iowa City, Iowa, USA[*1]Department of Otolaryngology- Head and Neck Surgery, Institute of Otolaryngology, PLA General Hospital, 28 Fuxing Road, Beijing 100853, China[*2]Department of Otolaryngology- Head and Neck Surgery, University of Iowa, Iowa City, IA 52242, USA
推荐引用方式(GB/T 7714)：
Liang Zong,Jing Guan,Megan Ealy,et al.Mutations in apoptosis-inducing factor cause X-linked recessive auditory neuropathy spectrum disorder.[J].JOURNAL OF MEDICAL GENETICS.2015,52(8):523-531.doi:10.1136/jmedgenet-2014-102961.
APA：
Liang Zong,Jing Guan,Megan Ealy,Qiujing Zhang,Dayong Wang...&Qiuju Wang.(2015).Mutations in apoptosis-inducing factor cause X-linked recessive auditory neuropathy spectrum disorder..JOURNAL OF MEDICAL GENETICS,52,(8)
MLA：
Liang Zong,et al."Mutations in apoptosis-inducing factor cause X-linked recessive auditory neuropathy spectrum disorder.".JOURNAL OF MEDICAL GENETICS 52..8(2015):523-531
