Mdc1a

INTRODUCTION/AIMS: Merosin is a protein complex located in the basement membrane of skeletal muscles and laminin α2-containing regions of the central and peripheral nervous systems. However, because of the prominence of muscle-related symptoms, peripheral neuropathy associated with merosin-deficient congenital muscular dystrophy type 1A (MDC1A) has received little clinical attention. This study aimed to present pathological changes in intramuscular nerves of three patients with MDC1A and discuss their relationship with electrophysiological findings to provide new evidence of peripheral nerve involvement in MDC1A...

INTRODUCTION: Mutations of LAMA2 gene are associated with congenital muscular dystrophy (CMD). The LAMA2 -related CMD mainly consists of two diseases, merosin deficient congenital muscular dystrophies type 1A (MDC1A) and limb girdle muscular dystrophy 23 (LGMD23). LGMD23 is characterized by slowly progressive proximal muscle weakness, which primarily affects the lower limbs and results in gait difficulties. Additional clinical features include increased serum creatine kinase, abnormal electromyography with or without white matter abnormalities on brain imaging...

Background: Merosin-deficient congenital muscular dystrophy type 1A (MDC1A), also known as laminin-α2 chain-deficient congenital muscular dystrophy ( LAMA2 -MD), is an autosomal recessive disease caused by biallelic variants in the LAMA2 gene. In MDC1A, laminin- α2 chain expression is absent or significantly reduced, leading to some early-onset clinical symptoms including severe hypotonia, muscle weakness, skeletal deformity, non-ambulation, and respiratory insufficiency. Methods: Six patients from five unrelated Vietnamese families presenting with congenital muscular dystrophy were investigated...

Muscular dystrophies (MDs) comprise a diverse group of inherited disorders characterized by progressive muscle loss and weakness. Given the genetic etiology underlying MDs, researchers have explored the potential of CRISPR/Cas9 genome editing as a therapeutic intervention, resulting in significant advances. Here we review recent progress on the use of CRISPR/Cas9 genome editing as a potential therapy for MDs. Significant strides have been made in this realm, made possible through innovative techniques such as precision genetic editing by modified forms of CRISPR/Cas9...

LAMA2 -related muscular dystrophy (LAMA2 MD or MDC1A) is a devastating congenital muscular dystrophy that is caused by mutations in the LAMA2 gene encoding laminin-α2, the long chain of several heterotrimeric laminins. Laminins are essential components of the extracellular matrix that interface with underlying cells. The pathology of LAMA2 MD patients is dominated by an early-onset, severe muscular dystrophy that ultimately leads to death by respiratory insufficiency. However, pathology in nonmuscle tissues has been described...

Laminin-α2-related Congenital Muscular Dystrophy (LAMA2-CMD) is a neuromuscular disease affecting around 1-9/1,000,000 children. LAMA2-CMD is caused by mutations in the LAMA2 gene resulting in the loss of laminin-211/221 heterotrimers in skeletal muscle. LAMA2-CMD patients exhibit severe hypotonia and progressive muscle weakness. Currently, there is no effective treatment for LAMA2-CMD and patients die prematurely. The loss of laminin-α2 results in muscle degeneration, defective muscle repair, and dysregulation of multiple signaling pathways...

Merosin-deficient congenital muscular dystrophy (MDC1A) is an autosomal recessive disorder caused by mutations in the LAMA2 gene, resulting in a defective form of the extracellular matrix protein laminin-α2 (LAMA2). Individuals diagnosed with MDC1A exhibit progressive muscle wasting and declining neuromuscular functions. No treatments for this disorder are currently available. We previously showed that postnatal Lama1 upregulation, achieved through CRISPR activation (CRISPRa), compensates for Lama2 deficiency and prevents neuromuscular pathophysiology in a mouse model of MDC1A...

The laminin α2 (LAMA2) gene pathogenic variants can lead to limb-girdle muscular dystrophy (known as LGMDR23), which is rarely reported and characterized by proximal weakness in the limbs. We present the case of a 52-year-old woman who gradually developed weakness in both lower extremities since the age of 32 years. Magnetic resonance imaging (MRI) brain showed symmetrical sphenoid wings-like white matter demyelination in bilateral lateral ventricles. Electromyography showed quadriceps muscle damage on the bilateral lower extremity...

Technological advancements in molecular genetics and cytogenetics have led to the diagnostic definition of complex or atypical clinical pictures. In this paper, a genetic analysis identifies multimorbidities, one due to either a copy number variant or a chromosome aneuploidy, and a second due to biallelic sequence variants in a gene associated with an autosomal recessive disorder. We diagnosed the simultaneous presence of these conditions, which co-occurred by chance, in three unrelated patients: a 10q11.22q11...

LAMA2-related congenital muscular dystrophy (MDC1A), the most commonly recognized type of congenital muscular dystrophies, is a severe neonatal onset muscle disease caused by recessive mutations in the LAMA2 gene. Here, we established an induced pluripotent stem cell line from a MDC1A patient carrying a frameshift deletion c.3367delA in LAMA2 gene. The iPSC line expressed pluripotency markers, retained normal karyotype, showed capability of differentiating into three germ layers. The iPSC line will help to further elucidate the pathogenic mechanisms of LAMA2 mutation, and benefit treatment for congenital muscular dystrophies in the future...

LAMA2-related muscular dystrophy (LAMA2-MD) and SELENON(SEPN1)-related myopathy (SELENON-RM) are rare neuromuscular diseases caused by mutations in the LAMA2 and SELENON (SEPN1) gene, respectively. Systematic reviews on cardiac features in both neuromuscular diseases are lacking. This scoping review aims to elucidate the cardiac involvement in LAMA2-MD or SELENON-RM. Three electronic databases (PubMed, Embase and Cochrane) were searched. All studies, case reports and case series with information on cardiac features in LAMA2-MD or SELENON-RM patients were included...

No abstract text is available yet for this article.

LAMA2-related muscular dystrophy (LAMA2-MD) is classified into congenital muscular dystrophy type 1A (MDC1A) and autosomal recessive limb-girdle muscular dystrophy-23 (LGMDR23). The purpose of this study was to identify the involvement pattern of thigh muscles of LAMA2-MD patients on magnetic resonance imaging. Fourteen MDC1A and 3 LGMDR23 patients were included, with 21 known and 8 novel LAMA2 disease-causing variants. In LAMA2-MD, the gluteus maximus, anterior (quadriceps femoris) and posterior (adductor magnus and biceps femoris) thigh muscles were extensively and severely affected with fatty infiltration, with relatively sparing of the adductor longus...

Congenital muscular dystrophy type 1A (MDC1A), the most common congenital muscular dystrophy in Western countries, is caused by recessive mutations in LAMA2, the gene encoding laminin alpha 2. Currently, no cure or disease modifying therapy has been successfully developed for MDC1A. Examination of patient muscle biopsies revealed altered distribution of lysosomes. We hypothesized that this redistribution was a novel and potentially druggable aspect of disease pathogenesis. We explored this hypothesis using candyfloss (caf), a zebrafish model of MDC1A...

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 laminins (LM) are a family of basement membranes glycoproteins with essential structural roles in supporting epithelia, endothelia, nerves and muscle adhesion, and signaling roles in regulating cell migration, proliferation, stem cell maintenance and differentiation. Laminins are obligate heterotrimers comprised of α, β and γ chains that assemble intracellularly. However, extracellularly these heterotrimers then assemble into higher-order networks via interaction between their laminin N-terminal (LN) domains...

BACKGROUND: SELENON (SEPN1)-related myopathy (SELENON-RM) is a rare congenital myopathy characterized by slowly progressive proximal muscle weakness, early onset spine rigidity and respiratory insufficiency. A muscular dystrophy caused by mutations in the LAMA2 gene (LAMA2-related muscular dystrophy, LAMA2-MD) has a similar clinical phenotype, with either a severe, early-onset due to complete Laminin subunit α2 deficiency (merosin-deficient congenital muscular dystrophy type 1A (MDC1A)), or a mild, childhood- or adult-onset due to partial Laminin subunit α2 deficiency...

No abstract text is available yet for this article.

Recessive mutations in the LAMA2 gene lead to congenital muscular dystrophy type 1A and limb girdle muscular dystrophy R23 with complete or partial laminin α2 chain deficiency. Complete laminin α2 chain deficiency presents with early onset of severe hypotonia and generalized weakness, whereas partial deficiency shows a milder and more variable course with limb girdle weakness. Here, we report a child with mildly delayed motor development, elevated serum creatine kinase levels (>1000 U/l) and brain white matter hypointensity, indicative of laminin α2 chain deficiency...

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)...