title: Targeted next generation sequencing reveals a novel intragenic deletion of the LAMA2 gene in a patient with congenital muscular dystrophy.
abstract: Mutations in the LAMA2 gene cause laminin α‑2 (merosin)‑deficient congenital muscular dystrophies, which are autosomal recessive muscle disorders. Laminin α‑2 is widely expressed in the basement membrane of skeletal muscle, the myotendinous junctions and extra‑synaptically at neuromuscular synapses. In the present study, target next‑generation sequencing was used for mutation detection, and polymerase chain reaction (PCR) analysis and Sanger sequencing were used in the identification of small deletions. Subsequently, quantitative PCR (qPCR) was performed to characterize the identified deletion encompassing exon five of the LAMA2 gene. Two causative mutations were identified using target region sequencing which provided the additional information required to facilitate clinical diagnosis. One heterozygous mutation (p. Lys682LysfsX22) was identified and confirmed by Sanger sequencing, and another heterozygous mutation (Exon5del) was found and validated by qPCR. Co‑segregation analysis indicated that the Exon5del mutation originated from the proband's mother and the previously reported frameshift mutation (p. Lys682LysfsX22) was inherited from the proband's father. To the best of our knowledge, the present study was the first to report an entire exon five deletion in the LAMA2 gene.
authors.affiliation: Department of Research and Development, BGI‑Central China, Wuhan East Lake High‑Tech Development Zone, Wuhan, Hubei 430075, P.R. China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Neurology, Wuhan Medical and Health Center for Women and Children, Wuhan, Hubei 430016, P.R. China.
authors.forename: Bing
authors.initials: B
authors.lastname: Mao
authors.affiliation: Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430074, P.R. China.
authors.forename: Lixia
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Research and Development, BGI‑Central China, Wuhan East Lake High‑Tech Development Zone, Wuhan, Hubei 430075, P.R. China.
authors.forename: Liangwei
authors.initials: L
authors.lastname: Mao
authors.affiliation: Department of Obstetrics, Wuhan Medical and Health Center for Women and Children, Wuhan, Hubei 430016, P.R. China.
authors.forename: Aifen
authors.initials: A
authors.lastname: Zhou
authors.affiliation: Department of Obstetrics, Wuhan Medical and Health Center for Women and Children, Wuhan, Hubei 430016, P.R. China.
authors.forename: Jiangxia
authors.initials: J
authors.lastname: Cao
authors.affiliation: Department of Neurology, Wuhan Medical and Health Center for Women and Children, Wuhan, Hubei 430016, P.R. China.
authors.forename: Jiasheng
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Obstetrics, Wuhan Medical and Health Center for Women and Children, Wuhan, Hubei 430016, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Research and Development, BGI‑Shenzhen, Shenzhen, Guangdong 518083, P.R. China.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Department of Research and Development, BGI‑Shenzhen, Shenzhen, Guangdong 518083, P.R. China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Wei
authors.affiliation: Department of Research and Development, BGI‑Central China, Wuhan East Lake High‑Tech Development Zone, Wuhan, Hubei 430075, P.R. China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of Research and Development, BGI‑Central China, Wuhan East Lake High‑Tech Development Zone, Wuhan, Hubei 430075, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Mu
authors.affiliation: Department of Neurology, Wuhan Medical and Health Center for Women and Children, Wuhan, Hubei 430016, P.R. China.
authors.forename: Zhisheng
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000328:Adult; D000483:Alleles; D001483:Base Sequence; D001921:Brain / Q000473:pathology; D002648:Child; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D017353:Gene Deletion; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007797:Laminin / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D008969:Molecular Sequence Data; D009136:Muscular Dystrophies / Q000175:diagnosis / Q000235:genetics*; D009154:Mutation; D016415:Sequence Alignment
chemical_list: D007797:Laminin; C102645:laminin alpha 2