Phenotypic Intermediate Forms Overlapping to Emery-Dreifuss and Limb Girdle Muscular Dystrophies Caused by Lamin A/C Gene Mutations

Albuquerque, Marco Antônio Veloso; Pasqualin, Lívia M.A.; Martins, Cristiane Aparecida; Reed, Umbertina Conti; Zanoteli, Edmar

doi:10.1016/j.pediatrneurol.2014.01.036

Cited by 2 publications

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“…Muscular dystrophies are clinically, and genetically heterogeneous group of rare disorders characterized by progressive, generalized muscle weakness and cardiac manifestations 1 . Among them, limb‐girdle muscular dystrophy (LGMD) shares clinical features such as proximal and distal muscle weakness, which are limited to hips and shoulders 2,3 …”

Section: Introductionmentioning

confidence: 99%

A novel biallelic variant in the Popeye domain‐containing protein 1 (POPDC1) underlies limb girdle muscle dystrophy type 25

et al. 2022

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POPDC1 also known as BVES, is a highly conserved transmembrane protein, important for striated muscle function and homeostasis. Pathogenic variants in the POPDC1 gene are associated with limb‐girdle muscular dystrophy type 25 (LGMDR25). In the present study, we performed trio‐whole exome sequencing (WES) followed by Sanger sequencing on a single family having LGMD clinical features. Protein modeling of all POPDC1 missense variants (POPDC1Pro134Leu, POPDC1Ile193Ser, and POPDC1Ser201Phe) associated with LGMDR25 were performed using Molecular Dynamics (MD) simulation. We identified a homozygous missense variant (c.401C>T; p.Pro134Leu) in the POPDC1 gene. Altered 3D structure, disruptive fluctuation, less compactness, and instability were observed in all the three variants of POPDC1 protein models. In comparison, POPDC1Ser201Phe protein dynamics were more unstable than other variants. Functional study of newly identified variant would add key answers to underlying mechanisms of the disease.

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Section: Introductionmentioning

confidence: 99%

A novel biallelic variant in the Popeye domain‐containing protein 1 (POPDC1) underlies limb girdle muscle dystrophy type 25

et al. 2022

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Molecular Genetics ofEmery–Dreifuss Muscular Dystrophy

Meinke

2018

Encyclopedia of Life Sciences

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Emery–Dreifuss muscular dystrophy (EDMD) is a rare neuromuscular disorder typically characterised by early contractures, slowly progressive muscular wasting and life‐threatening heart conduction disturbances, which can develop into a cardiomyopathy. There is a wide intrafamilial and interfamilial clinical variability. Genetically, X‐linked recessive, autosomal dominant and autosomal recessive forms can be distinguished. Female carriers of the X‐linked forms may manifest with cardiac symptoms. By molecular genetic methods, EDMD can be associated with mutations in several genes encoding nuclear envelope proteins. These proteins are lamin A, emerin, FHL1, nesprins and SUN proteins. Still only approximately half of unrelated patients diagnosed with EDMD have a mutation in known genes pointing to further genetic heterogeneity in EDMD. The molecular pathogenesis is not fully resolved, but there are effects on signalling, mechanical stability and gene expression. Key Concepts Emery–Dreifuss muscular dystrophy (EDMD) is a neuromuscular disorder recognised clinically by three features: early contractures, a characteristic pattern of muscle wasting and cardiac conduction defects. EDMD was originally described as an X‐linked disorder, later found to be caused by mutations in the EMD gene encoding a nuclear membrane protein, emerin. Molecular genetic analysis allows precise subtyping of EDMD into X‐linked forms ( EMD and FHL1 associated), autosomal dominant forms ( LMNA , SYNE1 / SYNE2 associated) and autosomal recessive forms ( LMNA and SUN1 associated). Wide clinical variability of EDMD and clinical overlap with other clinical entities frequently require consideration of patients not completely fulfilling the EDMD diagnostic criteria for molecular genetic differentiation in EMD , LMNA , SYNE1/SYNE2 , SUN1 and FHL1 . Digenic pathogenesis has been observed including LMNA / EMD , LMNA / DES , SYNE1/SYNE2 , LMNA / SUN1 , LMNA / SUN2 and EMD / SUN1 . In all cases, EDMD mutations affect proteins located at the nuclear envelope where they interact with each other. Many patients do not have mutations in genes identified so far, so further genes are expected to be involved in the pathogenesis of EDMD.

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Phenotypic Intermediate Forms Overlapping to Emery-Dreifuss and Limb Girdle Muscular Dystrophies Caused by Lamin A/C Gene Mutations

Cited by 2 publications

References 3 publications

A novel biallelic variant in the Popeye domain‐containing protein 1 (POPDC1) underlies limb girdle muscle dystrophy type 25

A novel biallelic variant in the Popeye domain‐containing protein 1 (POPDC1) underlies limb girdle muscle dystrophy type 25

Molecular Genetics ofEmery–Dreifuss Muscular Dystrophy

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