Analysis of clinical phenotype and genetic variants in a child with mitochondrial F-S disease due to variants of FDXR gene / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical phenotype and genetic variants of a child suspected for mitochondrial F-S disease.@*METHODS@#A child with mitochondrial F-S disease who visited Department of Neurology, Hunan Provincial children's Hospital on November 5, 2020 was selected as research subject of this study. Clinical data of the child was collected. The child was subjected to whole exome sequencing (WES). Bioinformatics tools were used to analyze the pathogenic variants. Candidate variants were verified by Sanger sequencing of the child and her parents.@*RESULTS@#WES revealed that the child has harbored compound heterozygous variants of the FDXR gene, namely c.310C>T (p.R104C) and c.235C>T (p.R79C), which were inherited from her father and mother, respectively. Neither variant has been reported in HGMD, PubMed, 1000 Genomes, and dbSNP databases. Both of the variants have been suggested as deleterious according to the prediction results from different bioinformatics analysis software.@*CONCLUSION@#Mitochondrial diseases should be suspected for patients with multiple system involvement. The compound heterozygous variants of the FDXR gene probably underlay the disease in this child. Above finding has enriched the spectrum of FDXR gene mutations underlying mitochondrial F-S disease. WES can facilitate the diagnosis of mitochondrial F-S disease at the molecular level.

Analysis of clinical phenotype and gene variation of pyridoxine-dependent epilepsy caused by ALDH7A1 gene mutation / 中华神经科杂志

Objective:To analyze the clinical phenotype and genotype characteristics of children with pyridoxine-dependent epilepsy (PDE) and provide evidence for diagnosis.Methods:Clinical data of 3 children with PDE enrolled in the Department of Neurology of Hunan Children′s Hospital from July 2016 to December 2020 were collected, and whole-exome sequencing (WES) was used for analysis. Pathogenic variants were analyzed and screened using bioinformatics tools combined with clinical phenotype. Sanger sequencing was used to analyze the source of mutations in children′s core family members.Results:Cases 1 (female) and 2 (male) were siblings, both of whom had convulsions within 24 hours after birth. WES results showed that the siblings carried compound heterozygous mutations of c.796C>T (p.R266 *) and c.1553G>C (p.R518T) in the ALDH7A1 gene, coming from the father and mother of the siblings respectively. Both of the mutations have been reported as pathogenic. Case 3, female, developed convulsions at the age of 1. WES results revealed that she carried compound heterozygous mutations of c.1094-109T>A and c.7C>T (p.R3C) in the ALDH7A1 gene, coming from her father and mother respectively. After searching HGMDPro, PubMed, 1000 Genomes, and dbSNP databases, both of the 2 mutations of c.1094-109T>A and c.7C>T (p.R3C) were not reported. The pathogenicity predictions of the 2 mutations were carried out by different biological information analysis software. The results showed that both of the mutations were harmful. All the 3 children had no epileptic seizures after treatment with increased doses of vitamin B6. Conclusions:When infants have unexplained convulsions, especially in the neonatal stage, PDE caused by ALDH7A1 gene mutation should be considered. Pyridoxine precision treatment has a good effect. The 2 de novo mutations of c.1094-109T>A and c.7C>T (p.R3C) enrich the mutation spectrum in the ALDH7A1 gene. WES has the auxiliary significance in the diagnosis of epilepsy.