Analysis of GFM1 gene mutations in a family with combined oxidative phosphorylation deficiency 1

Objective To analyze the clinical phenotype and genetic characteristics of a family with combined oxidative phosphorylation deficiency 1 (COXPD-1). Methods The whole exome sequencing was performed in parents of the proband; and the genetic defects were verified by Sanger sequencing technology in the dried blood spot of the proband, the amniotic fluid sample of the little brother of proband, and the peripheral blood of the parents. Results Whole exome sequencing and Sanger validation showed compound heterozygous mutations of GFM1 gene c.688G>A(p.G230S) and c.1576C>T (p.R526X) in both the proband and her little brother, and the c.1576C>T of GFM1 variant was first reported. The two patients were died in early infancy, and presented with metabolic acidosis, high lactic acid, abnormal liver function, feeding difficulties, microcephaly, development retardation and epilepsy. Conclusions GFM1 gene c.688G>A and c.1576C>T compound heterozygous mutations are the cause of this family of COXPD-1.