Novel LAMA2 Gene Mutations Associated with Merosin-Deficient Congenital Muscular Dystrophy

Background: Merosin-deficient congenital muscular dystrophy (MDC1A) is a rare autosomal recessive genetic disease occurred due to mutations in the LAMA2 gene. This study investigated the molecular genetics of three Iranian MDC1A patients who manifested hypotonia, muscle weakness at birth, elevated l...

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Bibliographic Details
Published in:Iranian biomedical journal 2018-11, Vol.22 (6), p.408
Main Authors: Hashemi-Gorji, Feyzollah, Yassaee, Vahid Reza, Dashti, Parisa, Miryounesi, Mohammad
Format: Article
Language:English
Subjects:
Autosomal recessive inheritance
Consents
Creatine
Creatine kinase
Deoxyribonucleic acid
Diagnosis
DNA
DNA sequencing
Dystrophy
Genetic counseling
Genetic screening
Genetics
Hypotonia
Kinases
Magnetic resonance imaging
Missense mutation
Muscles
Muscular dystrophy
Mutation
Next-generation sequencing
Nucleotide sequence
Peripheral blood
Prenatal diagnosis
RNA-directed DNA polymerase
Splicing
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Summary:Background: Merosin-deficient congenital muscular dystrophy (MDC1A) is a rare autosomal recessive genetic disease occurred due to mutations in the LAMA2 gene. This study investigated the molecular genetics of three Iranian MDC1A patients who manifested hypotonia, muscle weakness at birth, elevated levels of creatine kinase, and normal magnetic resonance imaging before the age of six months. Methods: Peripheral blood samples were collected from three unrelated patients and their families after obtaining informed written consents. Genomic DNA was extracted and sequenced using next-generation sequencing, followed by Sanger confirmation. Results: Sequencing results revealed a known missense mutation, c.8665G>A, and two novel heterozygous sequencing variants affecting splicing, c.397-4_c.478del and c.7452-1G>A, in the LAMA2 gene. Reverse transcriptase-PCR analysis showed that a new intronic variant, c.7452-1G>A, produced aberrant splicing pattern in the patient. Conclusions: This study expands the mutation spectrum of LAMA2 and assists in the diagnosis, genetic counseling, and prenatal diagnosis of the affected families.
ISSN:1028-852X
2008-823X
DOI:10.29252/ibj.22.6.408