A Novel Mutation in the Choline Kinase Beta Gene in an Iranian Kindred

Introduction: Mutations in the choline kinase beta (CHKB) gene are associated with a congenital musculardystrophy with giant mitochondria at the periphery of muscle fibers called megaconial congenital musculardystrophy (MDCMC). This form of recessively inherited disease is characterized with early onset rostrocaudalmuscular dystrophy accompanied with a combination of mental retardation, microcephaly, delayed development,dilated cardiomyopathy, skin changes and facial dysmorphism. To the best of our knowledge, there is currently31 cases of MDCMC reported worldwide. This study reports a case of an Iranian family with 2 confirmed casesof MDCMC bearing a novel homozygous mutation.Methods: The DNA sample of the patient was amplified for all eleven CHKB exons and exon-intron boundariesthrough PCR technique, followed by Sanger sequencing.Results: Patient had elevated CK (4809 IU/L, > 20 times normal). Electrophysiologic testing showed normalNCS and an irritable myopathic pattern. Muscle biopsy revealed mild dystrophic features accompanied withincreased internalized nuclei and few nuclear clumps. In modified Gomori Trichrome stain we observed largeand mainly peripherally-located mitochondrias and one red-rimmed vacuole. Central areas were devoid ofmitochondrias on Cox and SDH. A novel homozygous mutation (c.260T> C leu87pro) was identified in exon 2 ofCHKB gene which confirmed by co-segregation of the second affected family member. Functional analysisconfirmed the mutation as disease causing or damaging .Conclusion: We report an Iranian family with two confirmed (and two probable) MDCMC bearing a novelhomozygous mutation in the CHKB gene, which alters leucine to proline.

Keywords:

Congenital muscular dystrophy , Megaconial myopathy , Novel mutation , Choline kinase beta , Mental retardation