Distal myopathy with coexisting heterozygous TIA1 and MYH7 Variants.
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.
Department of Neurology, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA.
Patricio
P
Brand
Department of Neurology, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA.
P James B
PJ
Dyck
PreventionGenetics, 3800 S. Business Park Ave, Marshfield, Wisconsin 54449, USA; Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Jie
J
Liu
Department of Neurology, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA.
Sarah
S
Berini
Department of Neurology, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA.
Duygu
D
Selcen
Department of Neurology, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA. Electronic address: Milone.Margherita@mayo.edu.
Margherita
M
Milone
D000368:Aged; D024722:Cardiac Myosins / Q000235:genetics*; D049310:Distal Myopathies / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000473:pathology; D018995:Myosin Heavy Chains / Q000235:genetics*; D010375:Pedigree; D035781:Siblings; D000074019:T-Cell Intracellular Antigen-1 / Q000235:genetics*
C501641:MYH7 protein, human; D000074019:T-Cell Intracellular Antigen-1; C071558:TIA1 protein, human; D024722:Cardiac Myosins; D018995:Myosin Heavy Chains
Digenic myopathy; Distal myopathy; Hypertrophic cardiomyopathy; MYH7; TIA1