Merosin-deficient congenital muscular dystrophy: A novel homozygous mutation in the laminin-2 gene

Turner, Clinton; Mein, R.; Sharpe, Cynthia; Love, Donald R.

doi:10.1016/j.jocn.2015.04.016

Cited by 5 publications

(3 citation statements)

References 20 publications

(16 reference statements)

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“… 5 , 6 The various mutations in the LAMA2 gene (with 65 exons) are the main cause of MDC1A. 7 Other major factors involved in congenital muscular dystrophies are presented in Figure 1 .…”

Section: Introductionmentioning

confidence: 99%

Identification of a compound heterozygous missense mutation in LAMA2 gene from a patient with merosin‐deficient congenital muscular dystrophy type 1A

Khorrami

Goleij

Karamad

et al. 2021

Clinical Laboratory Analysis

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Background Merosin‐deficient congenital muscular dystrophy type 1A (MDC1A) is occurred by mutations in LAMA2 gene that encodes the laminin α2 chain (merosin). MDC1A is a predominant subtype of congenital muscular dystrophy. Herein, we identified two missense mutations in LAMA2 gene in compound heterozygous status in an Iranian patient with MDC1A using whole‐exome sequencing (WES). Methods In the present study, we evaluated genetic alterations in an Iranian 35‐month‐old boy with MDC1A and his healthy family using WES method. The identified mutations further confirmed by Sanger sequencing method. Finally, in silico analysis was conducted to further evaluation of molecular function of the identified genetic variants. Results We identified two potentially pathogenic missense mutations in compound heterozygous state (c.7681G>A p.Gly2561Ser and c.4840A>G p.Asn1614Asp) in LAMA2 gene as contributing to the MDC1A phenotype. The healthy parents of our proband are single heterozygous for identified mutations. These variants were found to be pathogenic by in silico analysis. Conclusions In general, we successfully identified LAMA2 gene mutations in an Iranian patient with MDC1A using WES. The identified mutations in LAMA2 gene can be useful in genetic counseling, prenatal diagnosis, and predicting prognosis of MDC1A.

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“… 5 , 6 The various mutations in the LAMA2 gene (with 65 exons) are the main cause of MDC1A. 7 Other major factors involved in congenital muscular dystrophies are presented in Figure 1 .…”

Section: Introductionmentioning

confidence: 99%

Identification of a compound heterozygous missense mutation in LAMA2 gene from a patient with merosin‐deficient congenital muscular dystrophy type 1A

Khorrami

Goleij

Karamad

et al. 2021

Clinical Laboratory Analysis

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“…First described in 1994 by Tome et al, it is one of the most common forms of CMD [3]. The cellular defect results in the premature truncation, and thereby defective function of the laminin-211 glycoprotein, which plays a crucial role in establishing the structural and functional scaffolding between the basement membrane and the extracellular matrix in cardiac muscle, skeletal muscle, Schwann cells, oligodendrocytes and trophoblasts [1,[4][5][6][7][8]. The mechanical stress on muscle fibers without basement membrane support from laminin-211 leads to progressive muscle injury and atrophy, resulting in inflammation, scarring and elevation of creatinine phosphokinase (CPK) levels.…”

Section: Introductionmentioning

confidence: 99%

Anesthetic Care of a Child With Merosin-Deficient Muscular Dystrophy

2020

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Merosin-deficient congenital muscular dystrophy (MDCMD) is a progressive autosomal recessive disorder caused by the lack of expression of the α 2-chain of laminin-211 glycoprotein. The defect results in skeletal muscle dysfunction with severe muscle weakness, hypotonia, proximal joint contractures, facial dysmorphism, and late or failed ambulation. Given the progressive neuromuscular involvement and the potential for neuromuscular scoliosis, patients frequently require anesthetic care during surgical procedures to correct orthopedic deformities. We present a 9-year-old girl with MDCMD who required anesthetic care during insertion of growing rods to correct neuromuscular scoliosis. Previous reports of anesthetic care for patients with MDCMD are presented and options for perioperative care are reviewed.

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“…A previous study has shown a correlation between the levels of merosin expression and clinical severity[6]. The disorder is caused by the mutations in the LAMA2 (Gene ID: 3908, OMIM: 156225) on chromosome 6q22, which encodes the α2 chain subunit of laminin 2 (merosin) and laminin 4 (s-merosin)[7]. A recessive mutation in this gene also causes a wide phenotypic spectrum of LAMA2 -related muscular dystrophy from a severe early-onset CMD to a mild later childhood-onset limb-girdle type muscular dystrophy[8-10].…”

Section: Introductionmentioning

confidence: 99%

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

Hashemi‐Gorji

Yassaee

Dashti

et al. 2018

IBJ

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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.Conclusion:This study expands the mutation spectrum of LAMA2 and assists in the diagnosis, genetic counseling, and prenatal diagnosis of the affected families.

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Merosin-deficient congenital muscular dystrophy: A novel homozygous mutation in the laminin-2 gene

Cited by 5 publications

References 20 publications

Identification of a compound heterozygous missense mutation in LAMA2 gene from a patient with merosin‐deficient congenital muscular dystrophy type 1A

Identification of a compound heterozygous missense mutation in LAMA2 gene from a patient with merosin‐deficient congenital muscular dystrophy type 1A

Anesthetic Care of a Child With Merosin-Deficient Muscular Dystrophy

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

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