A rare case of dysferlinopathy with paternal isodisomy for chromosome 2 determined by exome sequencing

BACKGROUND: Dysferlinopathies are autosomal recessive muscular dystrophies resulting from defects in DYSF (MIM: 603009), which is located on chromosome 2p13 and encodes the dysferlin protein. METHODS: We performed exome sequencing and subsequent trio‐based analysis in a family with dysferlinopathy. RESULTS: We report a young patient presenting with hyperCKemia and mild muscle weakness of the lower limbs. Exome sequencing of the proband revealed a homozygous frameshift mutation, NM_001130987.2:c.1471dupA(p.M491Nfs*15), in DYSF. The father was heterozygous for the mutation and the mother did not carry the mutation, as determined by genetic analyses, exome sequencing of parental samples, and a trio‐based analysis. Further analysis revealed that the DYSF gene was not deleted; instead, the entire chromosome 2 of the proband was inherited from the father. Thus, the child had paternal uniparental isodisomy for chromosome 2 (uniparental disomy [UPD]2 pat). CONCLUSION: We report the first case of dysferlinopathy caused by paternal isodisomy for chromosome 2. Furthermore, our findings highlight the importance of exome sequencing of the proband and parents and trio analyses in clinical settings, particularly when Mendelian inheritance cannot be confirmed, to identify the presence of UPD and to rule out large pathogenic deletions.