Abstract
TIA1 mutations cause Welander distal myopathy. MYH7 mutations result in various clinical phenotypes, including Laing distal myopathy and cardiomyopathy. We describe a family with coexisting TIA1 and MYH7 variants. The proband is a 67-year-old woman with easy tripping since childhood and progressive asymmetric distal limb weakness, but no cardiac involvement. Muscle biopsy showed rare rimmed vacuoles, minicore-like structures and congophilic inclusions. Her 66-year-old sister has a mild distal myopathy, supraventricular tachycardia and hypertrophic cardiomyopathy. Both sisters carry the only known pathogenic TIA1 mutation and a heterozygous MYH7 variant (c.5459G > A; p.Arg1820Gln). Another sibling with isolated distal myopathy carries only the TIA1 mutation. MYH7 p.Arg1820Gln involves a highly conserved residue and is predicted to be deleterious. Furthermore, the proband's childhood-onset distal leg weakness and sister's cardiomyopathy suggest that MYH7 p.Arg1820Gln likely affects function, favoring a digenic etiology of the myopathy.
Original language | English (US) |
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Pages (from-to) | 511-515 |
Number of pages | 5 |
Journal | Neuromuscular Disorders |
Volume | 26 |
Issue number | 8 |
DOIs | |
State | Published - Aug 1 2016 |
Keywords
- Digenic myopathy
- Distal myopathy
- Hypertrophic cardiomyopathy
- MYH7
- TIA1
ASJC Scopus subject areas
- Pediatrics, Perinatology, and Child Health
- Neurology
- Clinical Neurology
- Genetics(clinical)