Castro-Gago Manuel, Dacruz-Alvarez David, Pintos-Martínez Elena, Beiras-Iglesias Andrés, Delmiro Aitor, Arenas Joaquín, Martín Miguel Ángel, Martínez-Azorín Francisco
Servicio de Neuropediatría, Departamento de Pediatría, Hospital Clínico Universitario, Facultad de Medicina, Santiago de Compostela, Spain.
Servicio de Anatomía Patológica, Hospital Clínico Universitario, Facultad de Medicina, Santiago de Compostela, Spain.
Eur J Paediatr Neurol. 2014 Nov;18(6):796-800. doi: 10.1016/j.ejpn.2014.06.005. Epub 2014 Jun 20.
Choline kinase beta gene (CHKB) mutations have been identified in Megaconial Congenital Muscular Dystrophy (MDCMC) patients, but never in patients with an additional combined deficiency of complexes I, III and IV and mitochondrial DNA (mtDNA) depletion.
To report mutations in carry genes for MDCMC with respiratory chain defects and mtDNA depletion.
Whole-exome sequencing (WES) was used to identify the carry genes in a Spanish child with muscle weakness, mild hypotonia at lower limb muscles, mildly elevated creatine kinase (CK), enlarged mitochondria in the periphery of the fibers, combined deficiency of complex I, III and IV and depletion of mtDNA.
With WES data, it was possible to get the whole mtDNA sequencing and discard any pathogenic variant in this genome. The first filter of WES data with the nuclear-encoded mitochondrial genes (MitoCarta) did not get any candidate. However, the analysis of whole exome uncovered a homozygous nonsense pathogenic mutation in CHKB gene (NM_005198.4:c.810T>A, p.Tyr270*).
Our data confirm the role of CHKB in MDCMC and point to this gene as unique candidate for the combined deficiency of respiratory chain and mtDNA depletion observed in this patient.
在大空泡先天性肌营养不良（MDCMC）患者中已鉴定出胆碱激酶β基因（CHKB）突变，但在伴有复合物I、III和IV联合缺陷以及线粒体DNA（mtDNA）耗竭的患者中从未发现过。
报告伴有呼吸链缺陷和mtDNA耗竭的MDCMC相关基因的突变情况。
采用全外显子组测序（WES）来鉴定一名患有肌无力、下肢肌肉轻度张力减退、肌酸激酶（CK）轻度升高、纤维外周线粒体增大、复合物I、III和IV联合缺陷以及mtDNA耗竭的西班牙儿童的相关基因。
利用WES数据，得以完成整个mtDNA测序并排除该基因组中的任何致病变异。对带有核编码线粒体基因（线粒体编码基因集）的WES数据进行首轮筛选未得到任何候选基因。然而，对整个外显子组的分析发现CHKB基因存在纯合无义致病变异（NM_005198.4:c.810T>A，p.Tyr270*）。
我们的数据证实了CHKB在MDCMC中的作用，并指出该基因是此患者中观察到的呼吸链联合缺陷和mtDNA耗竭的唯一候选基因。
