title: Phenotype-Genotype Analysis of Chinese Patients with Early-Onset LMNA-Related Muscular Dystrophy.
abstract: This study aimed to analyze the correlation between the phenotype and genotype of Chinese patients with early-onset lamin A (LMNA)-related muscular dystrophy (MD). The clinical and myopathological data of 21 Chinese pediatric patients with early-onset LMNA-related MD were collected and analyzed. LMNA gene mutation analysis was performed by direct sequencing of genomic DNA. Sublocalization of wild-type and mutant proteins were observed by immunofluorescence using cultured fibroblasts and human embryonic kidney 293 (HEK 293) cell. Seven patients were diagnosed with Emery-Dreifuss muscular dystrophy (EDMD) and 14 were diagnosed with LMNA-associated congenital muscular dystrophy (L-CMD). Four biopsy specimens from the L-CMD cases exhibited inflammatory changes. Abnormal nuclear morphology was observed with both transmission electron microscopy and lamin A/C staining. We identified 10 novel and nine known LMNA gene mutations in the 21 patients. Some mutations (c.91G>A, c.94_96delAAG, c.116A>G, c.745C>T, c.746G>A, and c.1580G>C) were well correlated with EDMD or L-CMD. LMNA-related MD has a common symptom triad of muscle weakness, joint contractures, and cardiac involvement, but the severity of symptoms and disease progression differ greatly. Inflammatory change in biopsied muscle is a characteristic of early-stage L-CMD. Phenotype-genotype analysis determines that some mutations are well correlated with LMNA-related MD.
authors.affiliation: Department of Pediatric, Peking University First Hospital, Beijing, China; Department of Neurology, The First Affiliated Hospital of Nanchang University, Nanchang, China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Tan
authors.affiliation: Department of Pediatric, Peking University First Hospital, Beijing, China.
authors.forename: Haipo
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Neurology, Peking University First Hospital, Beijing, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Neuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke/NIH, Bethesda, MD, United States of America.
authors.forename: Carsten
authors.initials: C
authors.lastname: Bonnemann
authors.affiliation: Department of Pediatric, Peking University First Hospital, Beijing, China.
authors.forename: Xingzhi
authors.initials: X
authors.lastname: Chang
authors.affiliation: Department of Pediatric, Peking University First Hospital, Beijing, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Nanchang University, Nanchang, China.
authors.forename: Yuchen
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Pediatric, Peking University First Hospital, Beijing, China.
authors.forename: Xiru
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Pediatric, Peking University First Hospital, Beijing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Xiong
mesh_terms: D002648:Child; D002675:Child, Preschool; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005838:Genotype; D006801:Humans; D007223:Infant; D034904:Lamin Type A / Q000235:genetics*; D008297:Male; D020389:Muscular Dystrophy, Emery-Dreifuss / Q000175:diagnosis / Q000235:genetics*; D020125:Mutation, Missense; D010641:Phenotype
chemical_list: C494847:LMNA protein, human; D034904:Lamin Type A