Juan Ding1, Dandan Zhao2, Renqian Du3, Yuehua Zhang1, Haipo Yang1, Jieyu Liu1, Chuanzhu Yan2, Feng Zhang3, Hui Xiong4. 1. Department of Pediatrics, Peking University First Hospital, Beijing 100034, China. 2. Department of Neurology, Shandong University Qilu Hospital, Jinan 250012, China. 3. School of Life Sciences, Fudan University, Shanghai 200433, China. 4. Department of Pediatrics, Peking University First Hospital, Beijing 100034, China. Electronic address: xh_bjbj@163.com.
Abstract
PURPOSE: 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. CONCLUSION: 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.
PURPOSE: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. CONCLUSION: 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: Min Wook Kim; Dae Hyun Jang; Jun Kang; Seungok Lee; Sun Young Joo; Ja Hyun Jang; Eun Hae Cho; Young Chul Choi; Jung Hwan Lee Journal: Ann Lab Med Date: 2017-07 Impact factor: 3.464
Authors: Chunping Qiao; Yi Dai; Viktoriya D Nikolova; Quan Jin; Jianbin Li; Bin Xiao; Juan Li; Sheryl S Moy; Xiao Xiao Journal: Mol Ther Methods Clin Dev Date: 2018-01-31 Impact factor: 6.698