title: Severe neurological manifestations in an Egyptian patient with a novel frameshift mutation in the Glutaryl-CoA dehydrogenase gene.
abstract: To characterize an Egyptian patient with glutaric acidemia type I (GA I) and to identify the causative mutation(s) that may be responsible for the disease phenotype. MRI was performed on the patient using the 1.5 T magnet, biochemical analysis was carried out using gas chromatography/mass spectrometry on the patient's dried blood spot, and the patient's organic acids were measured in dried blood and a urine sample using MS/MS and GC/MS, respectively. Total RNA was isolated from the patient's peripheral blood, and the synthesized cDNA was bi-directionally sequenced. The patient exhibited clinical features and MRI findings compatible with a diagnosis of GA I. The abnormal elevation of organic acids in the urine supported the presence of glutaryl-CoA dehydrogenase deficiency. Gene sequencing revealed a novel homozygous frameshift mutation, c.644_645insCTCG; p.(Pro217Leufs*14), in exon 8 of the GCDH gene. The present study revealed a novel frameshift mutation responsible for a severe GA I phenotype in an Egyptian patient. This novel mutation will ultimately contribute to a better understanding of the molecular pathology of the disease and shed light on the intricacies of the genotype-phenotype correlation of GA I disease.
authors.affiliation: Medical Genetics Unit, Pediatric Department, Faculty of Medicine, Ain Shams University Hospital, Cairo, 11665, Egypt.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Moseilhy
authors.affiliation: Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo, Egypt.
authors.forename: Magdy M
authors.initials: MM
authors.lastname: Hassan
authors.affiliation: Medical Genetics Unit, Department of Pediatrics, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
authors.forename: Heba S A
authors.initials: HS
authors.lastname: El Abd
authors.affiliation: Department of Radiodiagnosis, Faculty of Medicine, Ain-Shams University, Cairo, Egypt.
authors.forename: Shaimaa A
authors.initials: SA
authors.lastname: Mohammad
authors.affiliation: Laboratory of Biomedical Research, Virgen de la Victoria Clinical University Hospital, 29010, Málaga, Spain.
authors.forename: Rajaa
authors.initials: R
authors.lastname: El Bekay
authors.affiliation: Sidra Medical and Research Center, Doha, Qatar.
authors.forename: Ussama M
authors.initials: UM
authors.lastname: Abdel-Motal
authors.affiliation: Department of Biological & Environmental Sciences, College of Arts & Sciences, Qatar University, Doha, Qatar.
authors.forename: Allal
authors.initials: A
authors.lastname: Ouhtit
authors.affiliation: Medical Genetics Unit, Pediatric Department, Faculty of Medicine, Ain Shams University Hospital, Cairo, 11665, Egypt. ozaki@med.asu.edu.eg.|Medical Genetics Unit, Department of Pediatrics, Faculty of Medicine, Ain Shams University, Cairo, Egypt. ozaki@med.asu.edu.eg.
authors.forename: Osama K
authors.initials: OK
authors.lastname: Zaki
authors.affiliation: Biomedical Sciences Department, College of Health Sciences, Qatar University, Doha, Qatar. hatem.zayed@qu.edu.qa.
authors.forename: Hatem
authors.initials: H
authors.lastname: Zayed
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000000981:diagnostic imaging / Q000235:genetics*; D001921:Brain / Q000000981:diagnostic imaging; D001928:Brain Diseases, Metabolic / Q000000981:diagnostic imaging / Q000235:genetics*; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004534:Egypt; D017809:Fatal Outcome; D016368:Frameshift Mutation; D050770:Glutaryl-CoA Dehydrogenase / Q000172:deficiency* / Q000235:genetics*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D013058:Mass Spectrometry
chemical_list: D050770:Glutaryl-CoA Dehydrogenase
keywords: GC/MS; Glutaric acidemia type I; Glutaryl-CoA dehydrogenase; MRI; MS/MS