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: Dandan Tan, Haipo Yang, Yun Yuan, Carsten Bonnemann, Xingzhi Chang, Shuang Wang, Yuchen Wu, Xiru Wu, Hui Xiong
• Journal: PloS one (PLoS One) Vol. 10 Issue 6 Pg. e0129699 ( 2015) ISSN: 1932-6203 [Electronic] United States
• PMID: 26098624 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• LMNA protein, human
• Lamin Type A

Topics

• Child
• Child, Preschool
• Female
• Fibroblasts (metabolism)
• Genotype
• Humans
• Infant
• Lamin Type A (genetics)
• Male
• Muscular Dystrophy, Emery-Dreifuss (diagnosis, genetics)
• Mutation, Missense
• Phenotype