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Recessive ACTA1 variant causes congenital muscular dystrophy with rigid spine.

ABSTRACT: Variants in ACTA1, which encodes ?-skeletal actin, cause several congenital myopathies, most commonly nemaline myopathy. Autosomal recessive variants comprise approximately 10% of ACTA1 myopathy. All recessive variants reported to date have resulted in loss of skeletal ?-actin expression from muscle and severe weakness from birth. Targeted next-generation sequencing in two brothers with congenital muscular dystrophy with rigid spine revealed homozygous missense variants in ACTA1. Skeletal ?-actin expression was preserved in these patients. This report expands the clinical and histological phenotype of ACTA1 disease to include congenital muscular dystrophy with rigid spine and dystrophic features on muscle biopsy. This represents a new class of recessive ACTA1 variants, which do not abolish protein expression.

SUBMITTER: O'Grady GL

PROVIDER: S-EPMC4795062 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Recessive ACTA1 variant causes congenital muscular dystrophy with rigid spine.

O'Grady Gina L GL Best Heather A HA Oates Emily C EC Kaur Simranpreet S Charlton Amanda A Brammah Susan S Punetha Jaya J Kesari Akanchha A North Kathryn N KN Ilkovski Biljana B Hoffman Eric P EP Clarke Nigel F NF

European journal of human genetics : EJHG 20140903 6

Variants in ACTA1, which encodes α-skeletal actin, cause several congenital myopathies, most commonly nemaline myopathy. Autosomal recessive variants comprise approximately 10% of ACTA1 myopathy. All recessive variants reported to date have resulted in loss of skeletal α-actin expression from muscle and severe weakness from birth. Targeted next-generation sequencing in two brothers with congenital muscular dystrophy with rigid spine revealed homozygous missense variants in ACTA1. Skeletal α-acti ...[more]

PMID: 25182138

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