Abstract
Dystroglycanopathies are a genetically heterogeneous subset of congenital muscular dystrophies that exhibit autosomal recessive inheritance and are characterized by abnormal glycosylation of α-dystroglycan. In particular, POMT2 (protein O-mannosyltransferase-2) mutations have been identified in congenital muscular dystrophy patients with a wide range of clinical involvement, ranging from the severe muscle-eye-brain disease and Walker–Warburg syndrome to limb girdle muscular dystrophy without structural brain or ocular involvement. Cardiovascular disease is thought to be uncommon in congenital muscular dystrophy, with rare reports of cardiac involvement. We describe three brothers aged 21, 19, and 17 years with an apparently homozygous POMT2 mutation who all presented with congenital muscular dystrophy, intellectual disabilities, and distinct cardiac abnormalities. All three brothers were homozygous for a p.Tyr666Cys missense mutation in exon 19 of the POMT2 gene. On screening echocardiograms, all siblings demonstrated significant dilatation of the aortic root and depressed left ventricular systolic function and/or left ventricular wall motion abnormalities. Our report is the first to document an association between POMT2 mutations and aortopathy with concomitant depressed left ventricular systolic function. On the basis of our findings, we suggest patients with POMT2 gene mutations be screened not only for myocardial dysfunction but also for aortopathy. In addition, given the potential for progression of myocardial dysfunction and/or aortic dilatation, longitudinal surveillance imaging is recommended both for patients with disease as well as those that have normal baseline imaging.
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Martinez, H., Craigen, W., Ummat, M. et al. Novel cardiovascular findings in association with a POMT2 mutation: three siblings with α-dystroglycanopathy. Eur J Hum Genet 22, 486–491 (2014). https://doi.org/10.1038/ejhg.2013.165
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DOI: https://doi.org/10.1038/ejhg.2013.165
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