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.