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

Molecular Medicine Reports
Yun YangZhisheng Liu

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 r...Continue Reading

Citations

Jan 1, 1990·Muscle & Nerve·J R Mendell, J Florence
Mar 11, 2000·Neuromuscular Disorders : NMD·N Darin, M Tulinius
Apr 9, 2002·European Journal of Human Genetics : EJHG·Valérie Allamand, Pascale Guicheney
Aug 24, 2004·Diagnostic Molecular Pathology : the American Journal of Surgical Pathology, Part B·Lydia U YamamotoMariz Vainzof
Sep 9, 2005·Connective Tissue Research·Nobuharu SuzukiMotoyoshi Nomizu
Apr 18, 2007·Proceedings of the National Academy of Sciences of the United States of America·Thomas E HallPeter D Currie
Aug 15, 2008·Clinical Genetics·J OliveiraE Bronze-da-Rocha
May 8, 2009·Genome Research·Ruiqiang LiJun Wang
Jun 10, 2009·Bioinformatics·Heng Li1000 Genome Project Data Processing Subgroup
Jan 19, 2010·Bioinformatics·Heng Li, Richard Durbin
Jan 14, 2011·Science Translational Medicine·Callum J BellStephen F Kingsmore
Aug 4, 2011·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Melanie A JonesMadhuri R Hegde
Sep 14, 2011·Clinica Chimica Acta; International Journal of Clinical Chemistry·Xiaoming WeiXin Yi
Aug 18, 2012·Clinica Chimica Acta; International Journal of Clinical Chemistry·Xiaoming WeiXin Yi
Oct 19, 2012·Nature Reviews. Genetics·Leslie G BieseckerRon Zimmern
Dec 12, 2012·Acta Neuropathologica·Nasim Vasli, Jocelyn Laporte
May 18, 2013·Nature Reviews. Genetics·Sara Huston Katsanis, Nicholas Katsanis
Jun 15, 2013·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Mark A UmbargerGregory J Porreca
Oct 4, 2013·The New England Journal of Medicine·Yaping YangChristine M Eng
Jun 11, 2014·BMC Genomics·Chandra Sekhar Reddy ChilamakuriLeonardo A Meza-Zepeda

Related Concepts

Real-Time Polymerase Chain Reaction
Exons
LAMA2 gene
Brain
Myopathy
Gene Deletion Abnormality
Gene Deletion
Sequencing
Massively-Parallel Sequencing
Synapses

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