ITGA7 – Congenital Fiber-Type Disproportion Myopathy

Congenital fiber-type disproportion myopathy is characterized by type 1 fiber predominance and muscle weakness. A single autosomal recessive case links homozygous ITGA7 missense mutation p.Glu882Lys to CFTD in a proband presenting severe fiber-type disproportion and left ventricular non-compaction ([PMID:23800289]). The variant was absent from population databases and predicted deleterious, but no additional affected relatives or unrelated cases have been reported.

ITGA7 encodes the α7 integrin subunit of the laminin receptor in skeletal and cardiac muscle. Alternative splicing yields extracellular X1/X2 and cytoplasmic A/B isoforms with distinct laminin-binding affinities and developmental regulation ([PMID:8253814], [PMID:11744715], [PMID:12972542]). These studies confirm tissue-specific expression and receptor function but have not assessed the p.Glu882Lys variant. Pathogenicity likely arises from impaired integrin-mediated myofiber adhesion and maturation.

References

• Orphanet Journal of Rare Diseases | 2013 | Digenic mutational inheritance of the integrin alpha 7 and the myosin heavy chain 7B genes causes congenital myopathy with left ventricular non-compact cardiomyopathy PMID:23800289
• The Journal of Biological Chemistry | 1993 | Alternative extracellular and cytoplasmic domains of the integrin alpha 7 subunit are differentially expressed during development PMID:8253814
• Cell Adhesion and Communication | 1995 | An alternatively spliced exon in the extracellular domain of the human alpha 6 integrin subunit--functional analysis of the alpha 6 integrin variants PMID:7583007
• Molecular Biology of the Cell | 2003 | The beta1 cytoplasmic domain regulates the laminin-binding specificity of the alpha7X1 integrin PMID:12972542

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