FKRP相关常染色体隐性遗传肢带型肌营养不良9型患者2例的临床特征及基因变异分析  

Analysis of clinical characteristics and genetic variants in two children with Limb-girdle muscular dystrophy autosomal recessive 9 FKRP-related

作　　者：余婕 徐敏 丁乐[1] 黄艳军[1] 郭虎[1] 何燕 Yu Jie;Xu Min;Ding Le;Huang Yanjun;Guo Hu;He Yan(Department of Neurology,Children′s Hospital of Nanjing Medical University,Nanjing,Jiangsu 210008,China)

机构地区：[1]南京医科大学附属儿童医院神经内科,南京210008

出　　处：《中华医学遗传学杂志》2023年第10期1217-1221,共5页Chinese Journal of Medical Genetics

摘　　要：目的探讨FKRP相关常染色体隐性遗传肢带型肌营养不良9型(LGMD R9 FKRP-related)患者的基因型与表型的相关性。方法以2018年9月30日与2018年8月3日于南京医科大学附属儿童医院就诊的2例分别因心肌损害及肝功能损害就诊、经血清学检查为无症状的高磷酸肌酸激酶(CK)、疑似为进行性肌营养不良的患儿作为研究对象。收集患儿的临床资料,采集患儿及其父母的外周血样,进行全外显子组测序及Sanger测序家系验证。结果检测发现患儿1携带FKRP基因c.545A>G和c.941C>T复合杂合变异,二者均为已知变异,其中c.545A>G为中国人群中的热点变异;患儿2携带FKRP基因c.602T>C和c.961G>A复合杂合变异,二者既往均未见报道。结论结合2例患儿的临床特征及基因检测结果,确诊其为LGMD R9 FKRP-related。c.545A>G为中国人群LGMD R9 FKRP-related的热点变异,携带者症状较轻。相较于携带恶性变异的患者,本研究2例患儿均携带FKRP基因复合杂合错义变异,其症状相对较轻,仅表现为无症状的高CK。Objective To explore the correlation between clinical manifestations of limb-girdle muscular dystrophy autosomal recessive 9 FKRP-related(LGMD R9 FKRP-related)and variants of the FKRP gene.Methods Two children who had presented at the Children′s Hospital of Nanjing Medical University respectively due to increased serum myocardial zymogram and hepatic dysfunction on September 30,2018 and August 3,2018 were selected as the study subjects.Clinical data of the children were collected.Both children were suspected for Duchenne or Becker muscular dystrophy for asymptomatic high creatine kinase(CK)levels.Peripheral blood samples of the children and their parents were collected for whole exome sequencing,and candidate variants were validated by Sanger sequencing.Results Genetic testing revealed that both children have carried compound heterozygous variants of the FKRP gene.The c.545A>G and c.941C>T variants in child 1 have been reported previously,among which the c.545A>G is a hot spot mutation in the Chinese population.Child 2 has carried c.602T>C and c.961G>A variants,both of which were unreported previously.Conclusion Both children have met the diagnostic criteria for LGMD R9 FKRP-related.Carriers of the c.545A>G variant may present milder symptoms.Compared with patients carrying null variants,carriers of compound heterozygous missense variants may present with a milder phenotype,manifesting as asymptomatic high CK level.

关 键 词：FKRP相关常染色体隐性遗传肢带型肌营养不良9型 FKRP基因变异 基因型 表型 

分 类 号：R746.2[医药卫生—神经病学与精神病学]