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

Hashemi‐Gorji, Feyzollah; Yassaee, Vahid Reza; Dashti, Parisa; Miryounesi, Mohammad

doi:10.29252/.22.6.408

Cited by 13 publications

(15 citation statements)

References 26 publications

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“…In previous studies, patients with LAMA2 mutations, showed normal brain magnetic resonance imaging (MRI) when has been detected during the neonatal period or in the first 6 months of life [ 11 – 13 ]. However, white matter abnormalities have been shown in the later period of life except for the case of an Italian patient reported by Saredi et al [ 14 ], who carried a compound heterozygous nonsense mutation with an atypical phenotype and nearly normal brain MRI performed at 16 years of age.…”

Section: Discussionmentioning

confidence: 99%

Identification of a novel LAMA2 c.2217G > A, p.(Trp739*) mutation in a Moroccan patient with congenital muscular dystrophy: a case report

et al. 2021

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Background Merosin-deficient congenital muscular dystrophy type 1A (MDC1A) is a rare autosomal recessive genetic condition caused by deleterious mutations in the LAMA2 gene encoding the laminin-α2 chain. It is the most frequent subtype of congenital muscular dystrophies (CMDs) characterized by total laminin-α2 deficiency with muscle weakness at birth or in the first six months of life. To the best of our knowledge, this study reports the first molecular diagnosis and genetic defect of this heterogeneous form of CMD performed in a Moroccan medical genetic center using next-generation sequencing (NGS). It allows us to expand the mutational spectrum of the LAMA2 gene. Case presentation We report the case of a female Moroccan child with clinical and paraclinical features in favor of a CMD. She has global congenital hypotonia with generalized muscle weakness, psychomotor retardation, increased serum creatine kinase, and normal brain scan at the age of six months. Targeted NGS leads to the identification of a novel homozygous nonsense mutation c.2217G > A, p.(Trp739*) in the exon 16 of LAMA2. Sanger sequencing confirmed this mutation in the affected patient and showed that her parents are heterozygous carriers. Conclusions A modern genetic analysis by NGS improves the genetic diagnosis pathway for adequate genetic counseling of affected families more precisely. An accession number from the National Center for Biotechnology Information (NCBI) ClinVar database was retrieved for this novel LAMA2 mutation.

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Section: Discussionmentioning

confidence: 99%

Identification of a novel LAMA2 c.2217G > A, p.(Trp739*) mutation in a Moroccan patient with congenital muscular dystrophy: a case report

et al. 2021

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“…Merosin was absent in all patients. Hashemi-Gorji et al [ 47 ] identified a likely pathogenic missense variant, c.8665G>A (p.G2889R), in two unrelated Iranian boys of consanguineous parents. Both patients presented with a hypotonia since birth and elevated CK and aldolase in the first year of life.…”

Section: Discussionmentioning

confidence: 99%

“…One patient had kyphosis and contractures of elbow and wrist at age 7 years. Another patient also had kyphosis and normal cognitive function at age 6 years [ 47 ]. Recently, two homozygous variants, c.2882G>A (p.A961T) and c.4406G>A (p.C1469Y), were reported in a Chinese patient who presented with seizures, slight weakness of the proximal leg muscles, mild cognitive impairment, and severe leukoencephalopathy [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

Whole Exome Sequencing as a Diagnostic Tool for Unidentified Muscular Dystrophy in a Vietnamese Family

Nguyen

Ngọc

et al. 2020

Diagnostics

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Muscular dystrophies are a group of heterogeneous clinical and genetic disorders. Two siblings presented with characteristics like muscular dystrophy, abnormal white matter, and elevated serum creatine kinase level. The high throughput of whole exome sequencing (WES) makes it an efficient tool for obtaining a precise diagnosis without the need for immunohistochemistry. WES was performed in the two siblings and their parents, followed by prioritization of variants and validation by Sanger sequencing. Very rare variants with moderate to high predicted impact in genes associated with neuromuscular disorders were selected. We identified two pathogenic missense variants, c.778C>T (p.H260Y) and c.2987G>A (p.C996Y), in the LAMA2 gene (NM_000426.3), in the homozygous state in two siblings, and in the heterozygous state in their unaffected parents, which were confirmed by Sanger sequencing. Variant c.2987G>A has not been reported previously. These variants may lead to a change in the structure and function of laminin-α2, a member of the family of laminin-211, which is an extracellular matrix protein that functions to stabilize the basement membrane of muscle fibers during contractions. Overall, WES enabled an accurate diagnosis of both patients with LAMA2-related muscular dystrophy and expanded the spectrum of missense variants in LAMA2.

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“…ANK2 variant is mainly related to arrhythmia phenotypes [45]. LAMA2 is linked with muscular dystrophy [46]. SRRM2 is associated with Parkinson's disease and papillary thyroid carcinoma [47,48].…”

Section: Comparative Analysismentioning

confidence: 99%

Single nucleotide polymorphism mutation related genes in bladder cancer for the treatment of patients: a study based on the TCGA database

Long

Zhang

et al. 2020

Biotechnology & Biotechnological Equipment

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Bladder cancer (BLCA) is a common malignancy and has a poor prognosis. Single nucleotide polymorphisms (SNPs) in genes are closely associated with the tumorigenesis and tumor development and yet are not well illustrated in BLCA. In this study, we downloaded SNP-related data and transcriptome profiling of BLCA from the Cancer Genome Atlas (TCGA) database and identified high frequency mutation genes using Maftools package and differentially expressed genes (DEGs) between BLCA and normal bladder tissues by the Limma package. Then, the overlapping genes between high frequency mutation genes and DEGs were obtained by the Venn diagram tool. These overlapping genes were analyzed by Gene Ontology (GO) and Kyoto Gene and Genome Encyclopedia (KEGG) pathway enrichment analysis, protein-protein interaction (PPI) network construction, survival analysis and drug-gene interaction analysis. As a result, 33 overlapping mutant genes were obtained, which were enriched in multiple KEGG pathways (e.g. cellular senescence) and GO items (e.g. muscle organ development, costamere and actin binding). A significant gene module was constructed by PPI network analysis and included 12 hub genes (SYNE1, DMD, ATM, EP300, ANK2, LAMA2, FAT1, SRRM2, MACF1, TSC1, VCAN and RXRA). Moreover, ATM, RXRA, TSC1, DMD, EP300, LAMA2 and VCAN were drug targets. These findings provide important bioinformatics and theoretical basis for understanding the pathogenesis of BLCA and exploring the detailed mechanisms of mutant genes in the disease.

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

Cited by 13 publications

References 26 publications

Identification of a novel LAMA2 c.2217G > A, p.(Trp739*) mutation in a Moroccan patient with congenital muscular dystrophy: a case report

Identification of a novel LAMA2 c.2217G > A, p.(Trp739*) mutation in a Moroccan patient with congenital muscular dystrophy: a case report

Whole Exome Sequencing as a Diagnostic Tool for Unidentified Muscular Dystrophy in a Vietnamese Family

Single nucleotide polymorphism mutation related genes in bladder cancer for the treatment of patients: a study based on the TCGA database

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