Published in:
01-02-2017 | Original Article
Severe neurological manifestations in an Egyptian patient with a novel frameshift mutation in the Glutaryl-CoA dehydrogenase gene
Authors:
Ahmed Moseilhy, Magdy M. Hassan, Heba S. A. El Abd, Shaimaa A. Mohammad, Rajaa El Bekay, Ussama M. Abdel-Motal, Allal Ouhtit, Osama K. Zaki, Hatem Zayed
Published in:
Metabolic Brain Disease
|
Issue 1/2017
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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.