Differing disease phenotypes of Duchenne muscular dystrophy and Moyamoya disease in female siblings of a Korean family

BACKGROUND: Variable disease phenotypes can be influenced by several factors such as allelic variation, environmental factors, genetic modifiers, and genotype-environment interaction. Herein to the best of our knowledge, this is the first report of the coexistence of DMD and RNF213 gene mutations in a Korean family with differing disease phenotypes of Duchenne muscular dystrophy (DMD) and Moyamoya disease (MMD) in each female sibling. METHODS: Deletion or duplication of the exon in DMD was screened using multiplex ligation-dependent probe amplification (MLPA). Subsequently, single exon deletion or duplication identified by MLPA was confirmed by Sanger sequencing. On the other hand, a common missense mutation [NM_001256071.2:c.14429G>A (p.Arg4810Lys)] related to MMD in exon 60 of RNF213 was also identified by Sanger sequencing. RESULTS: Three female family members carried the same disease-causing mutations, c.9953_9954delAG of DMD and c.14429G>A of RNF213. Two (II-2 and II-3) of these siblings suffer from the disease but exhibited different DMD or MMD symptoms, while the mother (I-2) seemed almost unaffected. CONCLUSION: This report illustrates the difficulty that might be encountered in the interpretation of complex clinical manifestations when different genetic defects affecting neuromuscular and vascular diseases coexist.