Targeted next generation sequencing reveals a novel intragenic deletion of the LAMA2 gene in a patient with congenital muscular dystrophy

Yang,Yun; Mao,Bing; Wang,Lixia; Mao,Liangwei; Zhou,Aifen; Cao,Jiangxia; Hu,Jiasheng; Zhou,Yan; Pan,Yanhong; Wei,Xiaoming; Yang,Shuang; Mu,Feng; Liu,Zhisheng

doi:10.3892/mmr.2014.3135

Targeted next generation sequencing reveals a novel intragenic deletion of the LAMA2 gene in a patient with congenital muscular dystrophy

Authors:
- Yun Yang
- Bing Mao
- Lixia Wang
- Liangwei Mao
- Aifen Zhou
- Jiangxia Cao
- Jiasheng Hu
- Yan Zhou
- Yanhong Pan
- Xiaoming Wei
- Shuang Yang
- Feng Mu
- Zhisheng Liu
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Affiliations: Department of Research and Development, BGI‑Central China, Wuhan East Lake High‑Tech Development Zone, Wuhan, Hubei 430075, P.R. China, Department of Neurology, Wuhan Medical and Health Center for Women and Children, Wuhan, Hubei 430016, P.R. China, Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430074, P.R. China, Department of Obstetrics, Wuhan Medical and Health Center for Women and Children, Wuhan, Hubei 430016, P.R. China, Department of Research and Development, BGI‑Shenzhen, Shenzhen, Guangdong 518083, P.R. China
Published online on: December 24, 2014 https://doi.org/10.3892/mmr.2014.3135
Pages: 3687-3693

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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.

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