title: Clinical and molecular genetic analysis of a family with late-onset LAMA2-related muscular dystrophy.
abstract: OBJECTIVE
  LAMA2-related muscular dystrophy (LAMA2 MD) is an autosomal recessive inherited disease caused by LAMA2 gene mutation. The spectrum of the phenotype is expanding in recent years partially due to the definitive diagnosis of molecular genetics. We investigated the phenotype and genotype in a LAMA2 MD family manifesting as limb-girdle muscular dystrophy (LGMD).
  
  
  METHODS
  The clinical information of the proband and his family was collected. Muscle biopsy and immunohistochemical staining for the muscle specimen were performed. The genomic DNA of the family was extracted from the peripheral blood, and genetic testing was analyzed using the next generation sequencing and multiplex ligation dependent probe amplification (MLPA). The point mutation was verified by Sanger sequencing while exonic deletion was verified by array comparative genomic hybridization.
  
  
  RESULTS
  The patient had mild motor retardation when he was young, and no obvious weakness was reported. Muscle biopsy showed mild atrophy in histochemical staining. Immunohistochemical staining using antibody against merosin showed nearly normal expression surrounding the muscle fiber. The proband's sister had similar symptoms. By analyzing the gene test we found that compound heterozygous LAMA2 mutation inherited from the parents respectively. One coming from the father was a gross deletion expanding from exon 36 to exon 65. The other from the mother was a missense mutation c.1358G>C (p.Cys453Ser). Sanger sequencing verified the point mutation. Array comparative genomic hybridization confirmed a long stretch of deletion about 27.6-34.7 kb. The sister had the same mutations as the proband. We diagnosed the first late onset LAMA2 MD Chinese patients on molecular level and genetic counseling is available.
  
  
  CONCLUSIONS
  We investigated the phenotype and genotype in a family manifesting as limb-girdle muscular dystrophy (LGMD). This LAMA2 MD family manifesting as LGMD was identified in molecular genetic level and their phenotypes was described.
authors: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
authors: Juan
authors: J
authors: Ding
authors: Department of Neurology, Shandong University Qilu Hospital, Jinan 250012, China.
authors: Dandan
authors: D
authors: Zhao
authors: School of Life Sciences, Fudan University, Shanghai 200433, China.
authors: Renqian
authors: R
authors: Du
authors: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
authors: Yuehua
authors: Y
authors: Zhang
authors: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
authors: Haipo
authors: H
authors: Yang
authors: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
authors: Jieyu
authors: J
authors: Liu
authors: Department of Neurology, Shandong University Qilu Hospital, Jinan 250012, China.
authors: Chuanzhu
authors: C
authors: Yan
authors: School of Life Sciences, Fudan University, Shanghai 200433, China.
authors: Feng
authors: F
authors: Zhang
authors: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China. Electronic address: xh_bjbj@163.com.
authors: Hui
authors: H
authors: Xiong
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D055028:Comparative Genomic Hybridization; D005091:Exons; D005260:Female; D056726:Genetic Association Studies; D005820:Genetic Testing; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007797:Laminin / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D049288:Muscular Dystrophies, Limb-Girdle / Q000235:genetics*; D010375:Pedigree; D017354:Point Mutation; D017384:Sequence Deletion
chemical_list: D007797:Laminin; C102645:laminin alpha 2
keywords: Array comparative genomic hybridization; LAMA2; Limb-girdle muscular dystrophy; Multiplex ligation dependent probe amplification; The next generation sequencing