一个MYH9综合征家系2例耳聋患者临床特征及耳聋基因检测分析

Clinical features and analysis of deafness genes in 2 patients from a Chinese family with MYH9 disorder

目的分析一个MYH9综合征家系中2例耳聋患者的表型特征,进行候选耳聋基因的突变筛查,明确该家系耳聋表型的基因突变位点。方法对家系进行详细的病史问诊及体格检查、血常规及生化检查、听力学检测、外周血涂片瑞-吉染色及MYH9蛋白质免疫荧光检测;抽提2例患者外周血基因组DNA,使用全外显子组测序技术对包括所有已知的100多个耳聋相关基因进行筛查并对可疑突变进行Sanger测序验证。结果该家系所有患者有巨大血小板、血小板减少和中性粒细胞包涵体三联征,系谱分析符合常染色体显性遗传特征。本研究2例耳聋患者还伴有贫血、高脂血症和转氨酶升高;耳聋表现为语后性、迟发型和渐进性听力下降,以中高频听力损失为主的感音神经性耳聋。全外显子组测序技术检测到MYH9基因致病突变位点:c.G4546C:p.V1516L,未发现其他已知遗传性耳聋基因的致病突变。结论该家系2例患者的耳聋表型可能与MYH9致病突变p.V1516L相关。

Objective To investigate the clinical features of 2 deafness patients from a family with MYH9 disorder, and search the candidate genes related to deafness for mutation sites in this family. Methods Their detailed medical histories were surveyed. Physical examination, routine blood test, biochemical test, audiological test, and Wright-Giemsa staining and immunofluorescence assay of MYH9 protein in the peripheral blood smears were performed. Genomic DNA was extracted from the peripheral blood samples of 2 patients. More than 100 known genes associated with deafness were sequenced by whole exome sequencing, and the results were confirmed by Sanger sequencing. Results All affected members in this family had the typical triad of giant platelets, thrombocytopenia and neutrophil inclusion bodies, and the pedigree analysis revealed autosomal dominant inheritance. In this study, the 2 deaf patients also suffered from anemia, hyperlipidemia and elevated levels of transaminase. The features of their deafness were postlingual deafness, late-onset and progressive hearing loss, and medium and high frequency dominant sensorineural hearing loss. Whole exome sequencing indicated that the pathogenic mutation site of MYH9 gene was c.G4546 C:p.V1516L, and no other pathogenic mutations of known genes involved in deafness were found. Conclusion The deafness phenotype of the 2 patients in this family may be related to the MYH9 pathogenic mutation p.V1516L.