RT Journal Article SR Electronic T1 Clinical spectrum and genetic variations of LMNA-related muscular dystrophies in a large cohort of Chinese patients JF Journal of Medical Genetics JO J Med Genet FD BMJ Publishing Group Ltd SP 326 OP 333 DO 10.1136/jmedgenet-2019-106671 VO 58 IS 5 A1 Fan, Yanbin A1 Tan, Dandan A1 Song, Danyu A1 Zhang, Xu A1 Chang, Xingzhi A1 Wang, Zhaoxia A1 Zhang, Cheng A1 Chan, Sophelia Hoi-Shan A1 Wu, Qixi A1 Wu, Liwen A1 Wang, Shuang A1 Yan, Hui A1 Ge, Lin A1 Yang, Haipo A1 Mao, Bing A1 Bönnemann, Carsten A1 Liu, Jingying A1 Wang, Suxia A1 Yuan, Yun A1 Wu, Xiru A1 Zhang, Hong A1 Xiong, Hui YR 2021 UL http://jmg.bmj.com/content/58/5/326.abstract AB Background LMNA-related muscular dystrophy is caused by mutations in LMNA gene. We aimed to identify genetic variations and clinical features in a large cohort of Chinese patients with LMNA mutations in an attempt to establish genotype-phenotype correlation.Methods The clinical presentations of patients with LMNA-related muscular dystrophy were recorded using retrospective and prospective cohort study. LMNA mutation analysis was performed by Sanger sequencing or next-generation sequencing. Mosaicism was detected by personal genome machine amplicon deep sequencing for mosaicism.Results Eighty-four patients were identified to harbour LMNA mutations. Forty-one of those were diagnosed with LMNA-related congenital muscular dystrophy (L-CMD), 32 with Emery-Dreifuss muscular dystrophy (EDMD) and 11 with limb-girdle muscular dystrophy type 1B (LGMD1B). We identified 21 novel and 29 known LMNA mutations. Two frequent mutations were identified: c.745C>T and c.1357C>T. A correlation between the location of mutation and the clinical phenotype was observed: mutations affecting the head and coil 2A domains mainly occurred in L-CMD, while the coil 2B and Ig-like domains mainly related to EDMD and LGMD1B. We found somatic mosaicism in one parent of four probands. Muscle biopsies revealed 11 of 20 biopsied L-CMD exhibited inflammatory changes, and muscle cell ultrastructure showed abnormal nuclear morphology.Conclusions Our detailed clinical and genetic analysis of 84 patients with LMNA-related muscular dystrophy expands clinical spectrum and broadens genetic variations caused by LMNA mutations. We identified 21 novel and 29 known LMNA mutations and found two frequent mutations. A correlation between the location of mutation and the clinical severity was observed. Preliminary data suggested that low-dose corticosteroid treatment may be effective.The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information.