Clinical spectrum and genetic variations of LMNA-related muscular dystrophies in a large cohort of Chinese patients. Issue 5 (22nd June 2020)

• Record Type: Journal Article
• Authors: Fan, Yanbin; Tan, Dandan; Song, Danyu; Zhang, Xu; Chang, Xingzhi; Wang, Zhaoxia; Zhang, Cheng; Chan, Sophelia Hoi-Shan; Wu, Qixi; Wu, Liwen; Wang, Shuang; Yan, Hui; Ge, Lin; Yang, Haipo; Mao, Bing; Bönnemann, Carsten; Liu, Jingying; Wang, Suxia; Yuan, Yun; Wu, Xiru; Zhang, Hong; Xiong, Hui
• Is Part Of: Journal of medical genetics. Volume 58:Issue 5(2021)
• Page Start: 326
• Page End: 333
• Publication Date: 2020-06-22
• Subjects: clinical genetics -- muscle disease -- neuromuscular disease; Medical genetics -- Periodicals; 616.042
• DOI: 10.1136/jmedgenet-2019-106671
• Languages: English
• ISSNs: 1468-6244

Abstract

Abstract : 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.