Novel CHKB mutation expands the megaconial muscular dystrophy phenotype.

Introduction: Mutations in the choline kinase beta (CHKB) gene are associated with a congenital muscular dystrophy with giant mitochondria at the periphery of muscle fibers.

Methods: We describe a patient of Italian origin in whom whole-exome sequencing revealed a novel homozygous nonsense mutation, c.648C>A, p.(Tyr216*), in exon 5 of CHKB.

Results: The patient presented with limb-girdle weakness and hypotonia from birth with mental retardation, and had sudden and transient deteriorations of muscle strength with acute intercurrent illnesses. Previously undescribed sarcolemmal overexpression of utrophin was noted in the muscle biopsy.

Conclusions: Pathological features broaden the description of the entity and provide new insight in the pathogenic mechanisms. This case highlights the usefulness of next-generation sequencing in the diagnosis of rare and incompletely understood conditions.