CHEN Yinyi,ZHANG Ying&rsquo,ai,et al.Clinical features and analysis of deafness genes in 2 patients from a Chinese family with MYH9 disorder [J].J Third Mil Med Univ,2019,41(11):1083-1089.

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(/HTML )




Clinical features and analysis of deafness genes in 2 patients from a Chinese family with MYH9 disorder
CHEN Yinyi ZHANG Ying’ai GAO Xin CHEN Mei WANG Shunlan ZHANG Shufang

Central Laboratory, Affiliated Haikou Hospital of Xiangya Medical College, Central South University, Haikou, Hainan Province, 570208, China

MYH9 disorder deafness sensorineural whole exome sequencing gene mutation  
R394.5; R596.1; R764.43

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.G4546C: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.


[1]KELLEY M J, JAWIEN W, ORTEL T L, et al. Mutation of MYH9, encoding non-muscle myosin heavy chain A, in May-Hegglin anomaly[J]. Nat Genet, 2000, 26(1): 106-108. DOI:10.1038/79069.
[2]KUNISHIMA S, KOJIMA T, MATSUSHITA T, et al. Mutations in the NMMHC-A gene cause autosomal dominant macrothrombocytopenia with leukocyte inclusions (May-Hegglin anomaly/Sebastian syndrome)[J]. Blood, 2001, 97(4): 1147-1149. DOI:10.5050/KSNVE.2010.20.12.1153.
[3]石理华,刘乾,刘沙,等. 我国部分汉族人群MYH9多态性与终末期肾病的关联研究[J]. 中国免疫学杂志, 2016,32(1):79-82,89.DOI:10.3969/j.issn.1000-484X.2016.01.017.
SHI L H, LIU Q, LIU S, et al. Association of MYH9 SNPs with end-stage renal disease in Chinese Han population[J]. Chin J Immunol, 2016, 32(1): 79-82,89. DOI:10.3969/j.issn.1000-484X.2016.01.017.
[4]PECCI A, BIINO G, FIERRO T, et al. Alteration of liver enzymes is a feature of the MYH9-related disease syndrome[J]. PLoS ONE, 2012, 7(4): e35986. DOI:10.1371/journal.pone.0035986.
[5]PECCI A, MA X F, SAVOIA A, et al. MYH9: Structure, functions and role of non-muscle myosin ⅡA in human disease[J]. Gene, 2018, 664: 152-167. DOI:10.1016/j.gene.2018.04.048.
[6]ZHANG S F, ZHOU X Y, LIU S N, et al. MYH9-related disease: description of a large Chinese pedigree and a survey of reported mutations[J]. Acta Haematol, 2014, 132(2): 193-198. DOI:10.1159/000356681.
[7]PECCI A, VERVER E J, SCHLEGEL N, et al. Cochlear implantation is safe and effective in patients with MYH9-related disease[J]. Orphanet J Rare Dis, 2014, 9: 100. DOI:10.1186/1750-1172-9-100.
[8]CANZI P, PECCI A, MANFRIN M, et al. Severe to profound deafness may be associated with MYH9-related disease: report of 4 patients[J]. Acta Otorhinolaryngol Ital, 2016, 36(5): 415-420. DOI:10.14639/0392-100X-702.
[9]VERVER E J, TOPSAKAL V, KUNST H P, et al. Nonmuscle myosin heavy chain ⅡA mutation predicts severity and progression of sensorineural hearing loss in patients with MYH9-related disease[J]. Ear Hear, 2016, 37(1): 112-120. DOI:10.1097/AUD.0000000000000198.
[10]PECCI A, KLERSY C, GRESELE P, et al. MYH9-related disease: A novel prognostic model to predict the clinical evolution of the disease based on genotype-phenotype correlations[J]. Hum Mutat, 2014, 35(2): 236-247. DOI:10.1002/humu.22476.
[11]VERVER E, PECCI A, DE ROCCO D, et al. R705H mutation of MYH9 is associated with MYH9-related disease and not only with non-syndromic deafness DFNA17[J]. Clin Genet, 2015,88(1):85-89. DOI:10.1111/cge.12438.
[12]WASANO K, MATSUNAGA T, OGAWA K, et al. Late onset and high-frequency dominant hearing loss in a family with MYH9 disorder[J]. Eur Arch Otorhinolaryngol, 2016,273(11):3547-3552. DOI:10.1007/s00405-016-3954-0.
[13]WEI Q J, ZHU H M, QIAN X L, et al. Targeted genomic capture and massively parallel sequencing to identify novel variants causing Chinese hereditary hearing loss[J]. J Transl Med,2014,12:311.DOI:10.1186/s12967-014-0311-1.
[14]WANG C C, YUAN H J. Application and progress of high-throughput sequencing technologies in the research of hereditary hearing loss[J]. Hereditas, 2017,39(3):208-219. DOI:10.16288/j.yczz.16-376.
[15]EBRAHIM S, FUJITA T, MILLIS B A, et al. NMII forms a contractile transcellular sarcomeric network to regulate apical cell junctions and tissue geometry[J]. Curr Biol, 2013,23(8):731-736. DOI:10.1016/j.cub.2013.03.039.
[16]WU C C, LIN Y H, LU Y C, et al. Application of massively parallel sequencing to genetic diagnosis in multiplex families with idiopathic sensorineural hearing impairment[J]. PLoS ONE,2013,8(2):e57369. DOI:10.1371/journal.pone.0057369.
[17]DANTAS V G, LEZIROVITZ K, YAMAMOTO G L, et al. c.G2114A MYH9 mutation (DFNA17) causes non-syndromic autosomal dominant hearing loss in a Brazilian family[J]. Genet Mol Biol, 2014,37(4):616-621. DOI:10.1590/S1415-47572014005000025.
[18]KECSKEMTI N, SZNYI M, GBORJN A, et al. Analysis of GJB2 mutations and the clinical manifestation in a large Hungarian cohort[J]. Eur Arch Otorhinolaryngol, 2018,275(10): 2441-2448. DOI:10.1007/s00405-018-5083-4.
[19]XIA W J, LIU F, MA D. Research progress in pathogenic genes of hereditary non-syndromic mid-frequency deafness[J]. Front Med, 2016, 10(2): 137-142. DOI:10.1007/s11684-016-0449-8.


[1]王冰,姚红兵,徐洁,等.非综合征性耳聋儿童GJB2 235delC及线粒体DNA 12S rRNA A1555G 突变分析[J].第三军医大学学报,2009,31(15):1450.
 WANG Bing,YAO Hong-bing,XU Jie,et al.Screening of GJB2 235delC mutation and mtDNA 12S rRNA A1555G mutation in Chongqing children with non-syndromic hearing impairment[J].J Third Mil Med Univ,2009,31(11):1450.
 Hu Huamei,Hu Hua,Dong Yanling,et al.Mutation analysis of 9 mutation spots related to neonatal deafness by DNA microarray[J].J Third Mil Med Univ,2012,34(11):96.

更新日期/Last Update: 2019-06-06