进行性非综合征型聋家系临床表型及遗传学分析

目的分析一个连续五代常染色体显性遗传性非综合征型聋家系的临床表型及遗传学特征。方法对该耳聋家系成员进行病史采集、全身及听力学检查,绘制遗传图谱并进行遗传学特征分析。应用微卫星标记连锁分析方法及外显子序列分析对常染色体显性遗传(DFNA)23个基因的22个位点进行初步筛查。结果该耳聋家系共五代,现存家系成员44人,参与本研究的39人中耳聋患者16人,除1人为语前聋外,其他患者均表现为迟发性、渐进性听力下降,发病年龄介于14～40岁,早期以中频听力下降为主,逐渐累及高频,随着年龄的增长,呈全频听力下降。除DFNA5外,各DFNA位点连锁分析所得LOD值均<-2,提示该家系的致聋基因与这些位点均不连锁。对家系中2例患者和2例正常者DFNA5的所有外显子进行测序分析,未发现突变。结论该家系遗传方式符合常染色体显性遗传规律,表现为以中高频听力下降为主的感音神经性聋;对已知耳聋基因位点进行筛查,未发现明确的阳性位点;通过新一代测序技术进行全外显子组分析可能发现新的感音神经性聋致病基因。

Genetic and Audiological Characteristic of a Chinese Family with Autosomal Dominant Hereditary Nonsyndromic Hearing Loss

Objective To study the phenotype and genetic characteristic of a five-generation Chinese family with autosomal dominant nonsyndromic hearing loss. Methods Members of this family were interviewed to identify their medical histories of hearing loss.Detailed audiology examination was performed and clinical data of this family was collected.A pedigree diagram was drawn according to the hereditary information.Prescreening of 22 DFNA loci with 23 known DFNA genes by using microsatellite makers and linkage analysis and gene sequence analysis was performed. Results This family comprises 44 members.Thirty-nine family members anticipated showed prelingual onset.The other patients showed late-onset,progressive hearing loss,occurred between 14~40 years of age.The hearing loss began at the medium-frequency and whole frequencies became involved along with age.In addition to DFNA5,all other DFNA loci were less than-2,linkage analysis showed no linkages between pedigree gene and reported loci.Sequencing of the DFNA5 gene of 4 members(two patients and two normal) in this family found no mutation. Conclusion Pedigree analysis suggested an autosomal dominant inheritance pattern in this family.Positive linkage were not found in the known deafness loci we screened.The information should facilitate future gene identification by using next-generation sequencing technology for discovering of novel deafness genes.