What's new in neuromuscular disorders? The congenital myopathies

AbstractCongenital myopathies are an expanding spectrum of neuromuscular disorders with early infantile or childhood onset hypotonia and slowly or nonprogressive skeletal muscle weakness. RYR1-related myopathies are the most common and frequently diagnosed class of congenital myopathies. Malignant hyperthermia susceptibility and central core disease are autosomal dominant or de novo RYR1 disorder, whereas multiminicore, congenital fiber type disproportion and centronuclear myopathy are autosomal recessive RYR1 disorders. The presence of ptosis, ophthalmoparesis, facial, and proximal muscles weakness, with the presence of dusty cores and multiple internal nuclei on muscle biopsy are clues to the diagnosis. We describe an 18-year-old male, who presented with early infantile onset ptosis, ophthalmoplegia, myopathic facies, hanging lower jaw, and proximal muscle weakness confirmed as an RYR1-related congenital centronuclear myopathy on genetic analysis and muscle biopsy.

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M-line TTN Mutations in Salih Myopathy: Novel Biallelic Mutation and Review of the Literature

10.21203/rs.3.rs-743096/v1 ◽

2021 ◽

Author(s):

Youssef El Kadiri ◽

Ilham Ratbi ◽

Jaber Lyahyai ◽

Abdelaziz Sefiani

Keyword(s):

Next Generation Sequencing ◽

Sanger Sequencing ◽

Neuromuscular Disorders ◽

Genetic Diagnosis ◽

Congenital Myopathy ◽

Next Generation ◽

Congenital Myopathies ◽

Arab Population ◽

Truncating Mutation ◽

Generation Sequencing

Abstract Background: Salih myopathy (SALMY), also known as early-onset myopathy with fatal cardiomyopathy (EOMFC) is a rare, heterogeneous, and severe form of titinopathies with autosomal recessive inherited neuromuscular disorders that affects both skeletal and cardiac muscles. It was previously identified only in the Arab population with unknown incidence. TTN mutations that have been reported in congenital myopathies are associated with a variety of phenotypic spectrum of titinopathies, which are scattered along the 364 exons of the gene. We report a Moroccan family with an affected patient diagnosed with Salih myopathy by next-generation sequencing (NGS) with a literature review of this rare entity.Methods: Genetic investigation by NGS was performed in a consanguineous Moroccan female child aged 29 months with congenital myopathy. Sanger sequencing confirmation was performed on the patient and both of her parents. Clinical and molecular data of the patient were correlated with 14 patients reported in the literature for congenital myopathy associated with a heart defect or development of dilated cardiomyopathy with at least one mutation in the M-band titin protein as inclusion criteria. Results: Bioinformatics analysis of Clinical Exome Sequencing (CES) data identified a novel homozygous truncating mutation c.106541delA p.(Asp35514Valfs*32) in exon 361 of the TTN gene. Sanger sequencing confirmed the mutation at a homozygous state in the proband and that both her parents are heterozygous carriers. Conclusions: Application of next-generation sequencing in rare genetic heterogeneous forms as SALMY provides more evidently an increasing proportion of congenital myopathies than currently recognized and expands the mutation spectrum of the TTN gene for better guiding the genetic diagnosis with adequate genetic counseling to the Moroccan families.

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From Mice to Humans: An Overview of the Potentials and Limitations of Current Transgenic Mouse Models of Major Muscular Dystrophies and Congenital Myopathies

International Journal of Molecular Sciences ◽

10.3390/ijms21238935 ◽

2020 ◽

Vol 21 (23) ◽

pp. 8935

Author(s):

Mónika Sztretye ◽

László Szabó ◽

Nóra Dobrosi ◽

János Fodor ◽

Péter Szentesi ◽

...

Keyword(s):

Gene Therapy ◽

Transgenic Mouse ◽

Mouse Models ◽

Age Of Onset ◽

Neuromuscular Disorders ◽

Muscular Dystrophies ◽

Genetic Defects ◽

Transgenic Mouse Models ◽

Congenital Myopathies ◽

Time Point

Muscular dystrophies are a group of more than 160 different human neuromuscular disorders characterized by a progressive deterioration of muscle mass and strength. The causes, symptoms, age of onset, severity, and progression vary depending on the exact time point of diagnosis and the entity. Congenital myopathies are rare muscle diseases mostly present at birth that result from genetic defects. There are no known cures for congenital myopathies; however, recent advances in gene therapy are promising tools in providing treatment. This review gives an overview of the mouse models used to investigate the most common muscular dystrophies and congenital myopathies with emphasis on their potentials and limitations in respect to human applications.

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