Brand Patricio, Dyck P James B, Liu Jie, Berini Sarah, Selcen Duygu, Milone Margherita
Department of Neurology, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA.
PreventionGenetics, 3800 S. Business Park Ave, Marshfield, Wisconsin 54449, USA; Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Neuromuscul Disord. 2016 Aug;26(8):511-5. doi: 10.1016/j.nmd.2016.05.012. Epub 2016 May 24.
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.
TIA1基因突变导致韦兰德远端肌病。MYH7基因突变会导致多种临床表型，包括莱因远端肌病和心肌病。我们描述了一个同时存在TIA1和MYH7变异的家系。先证者是一名67岁女性，自幼易绊倒，有进行性不对称的远端肢体无力，但无心脏受累。肌肉活检显示有罕见的镶边空泡、微小核心样结构和嗜刚果红包涵体。她66岁的姐姐有轻度远端肌病、室上性心动过速和肥厚型心肌病。两姐妹都携带唯一已知的致病性TIA1突变和一个杂合的MYH7变异（c.5459G＞A；p.Arg1820Gln）。另一名患有孤立性远端肌病的兄弟姐妹仅携带TIA1突变。MYH7的p.Arg1820Gln涉及一个高度保守的残基，预计具有有害性。此外，先证者儿童期起病的远端腿部无力以及其姐姐的心肌病表明，MYH7的p.Arg1820Gln可能影响功能，支持该肌病的双基因病因。
