Phenotype–Genotype Analysis of Chinese Patients with Early-Onset LMNA-Related Muscular Dystrophy
| Autor: | Yun Yuan, Carsten G. Bönnemann, Shuang Wang, Yuchen Wu, Xingzhi Chang, Hui Xiong, Dandan Tan, Xiru Wu, Haipo Yang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Male
Pathology medicine.medical_specialty congenital hereditary and neonatal diseases and abnormalities Genotype Mutation Missense lcsh:Medicine Gene mutation LMNA Biopsy medicine Humans Muscular dystrophy lcsh:Science Child Multidisciplinary medicine.diagnostic_test integumentary system business.industry lcsh:R Muscle weakness Infant Fibroblasts medicine.disease Lamin Type A Hypotonia Muscular Dystrophy Emery-Dreifuss Phenotype Child Preschool Congenital muscular dystrophy lcsh:Q Female medicine.symptom business Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 10, Iss 6, p e0129699 (2015) |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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