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Article: Clinical spectrum and genetic variations of LMNA-related muscular dystrophies in a large cohort of Chinese patients

TitleClinical spectrum and genetic variations of LMNA-related muscular dystrophies in a large cohort of Chinese patients
Authors
Issue Date2020
PublisherBMJ Group. The Journal's web site is located at http://jmg.bmj.com/
Citation
Journal of Medical Genetics, 2020, Epub 2020-06-22 How to Cite?
AbstractBackground: 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.
Persistent Identifierhttp://hdl.handle.net/10722/290956
ISSN
2019 Impact Factor: 4.943
2015 SCImago Journal Rankings: 3.820

 

DC FieldValueLanguage
dc.contributor.authorFan, Y-
dc.contributor.authorTan, D-
dc.contributor.authorSong, D-
dc.contributor.authorZhang, X-
dc.contributor.authorChang, X-
dc.contributor.authorWang, Z-
dc.contributor.authorZhang, C-
dc.contributor.authorChan, HSS-
dc.contributor.authorWu, Q-
dc.contributor.authorW, L-
dc.contributor.authorWang, S-
dc.contributor.authorYan, H-
dc.contributor.authorGe, L-
dc.contributor.authorYang, H-
dc.contributor.authorMao, B-
dc.contributor.authorBönnemann, C-
dc.contributor.authorLiu, J-
dc.contributor.authorWang, S-
dc.contributor.authorYuan, Y-
dc.contributor.authorWu, X-
dc.contributor.authorZhang, H-
dc.contributor.authorXiong, H-
dc.date.accessioned2020-11-02T05:49:30Z-
dc.date.available2020-11-02T05:49:30Z-
dc.date.issued2020-
dc.identifier.citationJournal of Medical Genetics, 2020, Epub 2020-06-22-
dc.identifier.issn0022-2593-
dc.identifier.urihttp://hdl.handle.net/10722/290956-
dc.description.abstractBackground: 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.-
dc.languageeng-
dc.publisherBMJ Group. The Journal's web site is located at http://jmg.bmj.com/-
dc.relation.ispartofJournal of Medical Genetics-
dc.rightsJournal of Medical Genetics. Copyright © BMJ Group.-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleClinical spectrum and genetic variations of LMNA-related muscular dystrophies in a large cohort of Chinese patients-
dc.typeArticle-
dc.identifier.emailChan, HSS: sophehs@hku.hk-
dc.identifier.authorityChan, HSS=rp02210-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1136/jmedgenet-2019-106671-
dc.identifier.pmid32571898-
dc.identifier.hkuros317724-
dc.identifier.volumeEpub 2020-06-22-
dc.identifier.spagejmedgenet-
dc.identifier.epage2019-
dc.publisher.placeUnited Kingdom-
dc.identifier.issnl0022-2593-

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