肌巨蛋白基因新位点突变致遗传性肌病伴早期呼吸衰竭1例并文献复习  

A case report of hereditary myopathy with early respiratory failure caused by new point mutations of TTN gene and literature review

作　　者：熊明秀 张静[2] Xiong Ming-Xiu;Zhang Jing(School of Medicine,University of Electronic Science and Technology of China,Chengdu,Sichuan 610054,China;Department of Pulmonary and Critical Care Medicine,Sichuan Academy of Medical Sciences/Sichuan Provincial People's Hospital,Chengdu,Sichuan 610072,China)

机构地区：[1]电子科技大学医学院,四川成都610054 [2]四川省医学科学院·四川省人民医院呼吸与危重症医学科,四川成都610072

出　　处：《解放军医学杂志》2024年第6期651-655,共5页Medical Journal of Chinese People's Liberation Army

基　　金：四川省科技厅重点研发项目(2022YFS0107);四川省医学会青年创新基金(S19011)。

摘　　要：目的报道1例遗传性肌病伴早期呼吸衰竭(HMERF)的临床病理特征、基因突变位点、诊断与治疗情况并进行文献复习,以提高对该病的认识。方法回顾性分析2021年4月四川省人民医院收治的以呼吸衰竭为首发表现的遗传性肌病1例的临床资料、影像学检查、组织病理和基因测序结果,以及诊断与治疗情况。结合文献报道总结中国HMERF患者的临床特征。结果本病例表现为四肢无力、呼吸困难进行性加重,肌肉MRI显示小腿腓肠肌内侧头选择性脂肪浸润;肌巨蛋白(TTN)基因的两个突变位点来自双亲,分别为341外显子c.94828G>A(P.a31610t)和50外显子c.14915C>T(P.S.4972L),诊断为HMERF;采用支持性治疗措施。在PubMed数据库检索到近10年报道的诊断为HMERF的中国患者15例,发病年龄(26.1±17.0)岁,多为男性,均检出TTN基因突变,突变类型以c.95195C>T(p.P31732L)较多,其次为c.95134T>C(p.C31712R)。结论HMERF是由基因突变引起的罕见遗传性疾病,骨骼肌无力和呼吸肌无力是主要临床表现,临床症状可不典型,TTN基因的344外显子是常见突变位点。本病例突变位点位于TTN基因的341外显子c.94828G>A(P.a31610t)和50外显子c.14915C>T(P.S4972L),可能为HMERF的新遗传标记。Objective To report the clinicopathological features,gene mutation sites,diagnosis and treatment of a case of hereditary myopathy with early respiratory failure(HMERF),and review the literature to enhance the understanding of the disease.Methods A retrospective analysis was conducted on the clinical data,imaging examinations,histopathological and genetic sequencing results,as well as the diagnosis and treatment of a case of HMERF as the initial presenting symptom,admitted to Sichuan Provincial People's Hospital in April 2021.The clinical characteristics of Chinese patients with HMERF were summarized in conjunction with literature reports.Results This patient presented with limb weakness and progressive dyspnea.Magnetic resonance imaging(MRI)showed selective fat infiltration of the medial head of calf gastrocnemius muscle.Two mutation sites in titin(TTN)gene inherited from both parents were identified,exon 341 c.94828G>A(P.a31610t)and exon 50 c.14915C>T(P.S.4972L),leading to the diagnosis of HMERF.The patient received supportive therapy.The PubMed database was searched and 15 cases of HMERF were diagnosed in Chinese patients over the past decade.The onset age of these patients was(26.1±17.0)years,predominantly affecting males.All patients exhibited mutations in TTN gene.The most prevalent mutation was identified as c.95195C>T(p.P31732L),followed by c.95134T>C(p.C31712R).Conclusions HMERF is a rare genetic disease caused by genetic mutation,with skeletal muscle weakness and respiratory muscle weakness as the main clinical manifestations.Clinical symptoms can be atypical,and exon 344 of TTN gene is a common mutation site.The mutation sites in this case,located at exon 341 c.94828G>A(P.a31610t)and exon 50 c.14915C>T(P.S4972L)of the TTN gene,may represent novel genetic markers for HMERF.

关 键 词：遗传性肌病伴早期呼吸衰竭 肌巨蛋白 基因突变 

分 类 号：R562.25[医药卫生—呼吸系统]