OTOF mutations revealed by genetic analysis of hearing loss families including a potential temperature sensitive auditory neuropathy allele
OTOF mutations revealed by genetic analysis of hearing loss families including a potential temperature sensitive auditory neuropathy allele
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DOI：
10.1136/jmg.2005.038612
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发表时间：
2006-07-01
影响因子：
4
通讯作者：
Kimberling, W. J.
中科院分区：
文献类型：
--
作者：
Varga, R.;Avenarius, M. R.;Kimberling, W. J.
介绍：大多数儿童听力损失可以由遗传原因引起。非综合征性听力损失占儿童遗传性听力损失的80%，其中DFNB 1/GJB 2突变是最常见的原因。在儿童听力损失的第二层遗传原因是突变的DFNB 9/OTOF gene.Methods：总共，65隐性非综合征性听力损失的家庭进行了筛选基因分型与DFNB 9/OTOF基因。结果：在6个家系中发现了8个OTOF病理性变异。其中，Q829 X在两个家族中被发现。我们还注意到23个其他编码变异，认为没有病理。一个先前发表的错义等位基因I515 T被发现在杂合子状态中的一个人被观察到是温度敏感的听神经病phenotype.Conclusions：突变OTOF引起深刻的听力损失和一种类型的听力损失耳声发射被称为听神经病。
Introduction: The majority of hearing loss in children can be accounted for by genetic causes. Nonsyndromic hearing loss accounts for 80% of genetic hearing loss in children, with mutations in DFNB1/GJB2 being by far the most common cause. Among the second tier genetic causes of hearing loss in children are mutations in the DFNB9/OTOF gene.Methods: In total, 65 recessive non-syndromic hearing loss families were screened by genotyping for association with the DFNB9/OTOF gene. Families with genotypes consistent with linkage or uninformative for linkage to this gene region were further screened for mutations in the 48 known coding exons of otoferlin.Results: Eight OTOF pathological variants were discovered in six families. Of these, Q829X was found in two families. We also noted 23 other coding variant, believed to have no pathology. A previously published missense allele I515T was found in the heterozygous state in an individual who was observed to be temperature sensitive for the auditory neuropathy phenotype.Conclusions: Mutations in OTOF cause both profound hearing loss and a type of hearing loss where otoacoustic emissions are spared called auditory neuropathy.