Molecular diagnosis of mtDNA syndromes in Egyptian pediatric patients: a hospital-based study

Abstract Background MCDs, or mitochondrial disorders, are a major contributor to morbidity and mortality. There are few studies on the prevalence of gene mutations in pediatric MCD patients in Egypt. The objective of the current study was to determine the frequencies of the most prevalent mtDNA mutations in a group of Egyptian children with classical mitochondrial disorders. Methods Over two years, 140 pediatric patients clinically suspected of having classical mitochondrial disorders and 50 controls were examined for the most prevalent mtDNA mutations at Cairo University Children’s Hospital. Polymerase Chain Reaction/Restriction Fragment Length Polymorphism analyses were used to screen for the 17 most common mtDNA mutations (G3460A, G11778A, T14484C, T3271C, G13513A, A3243G, A8344G, G8363A, T9176C, T8993C/G, A8344G, T8356C, G8363A, C3303T, A3260G, A4300G, and C9997T) based on the suspected syndrome. To validate the abnormal patterns, direct sequencing was carried out. Results Of the 114 children evaluated, 54 were female and 60 were male, with a median age (range) of 3.5 years (7 months–16 years). 77 out of 114 (67.5%) patients were born into consanguineous marriages. Merely 1.8% of mtDNA point mutations were detected; of those with Leber’s hereditary optic neuropathy, only two had the homoplasmic pathogenic variant T14484C of MTND6 verified. Conclusions Screening for the most prevalent mtDNA mutations could be used as preliminary noninvasive testing for such syndromes. The low positive incidence raises the possibility that these mtDNA point mutations are not unique to pediatric patients in Egypt. Given Egypt’s high percentage of consanguineous marriage, the molecular pathogenesis of such disorders is suspected to be of nuclear genetic origin.