Molecular genetic study of glutaric aciduria, type I: Identification of a novel mutation
| Autor: | Mohammad Amin Tabatabaiefar, Mohammad Reza Pourreza, Najmeh Fattahi, Javad Tavakkoly Bazzaz, Reza Sharifi, Shahnaz Zarifi, Mojtaba Darbouy, Azam Ahmadi Shadmehri, Mahboobeh Koohiyan |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Proband medicine.medical_specialty Mutation Missense Biology Biochemistry 03 medical and health sciences symbols.namesake Exon 0302 clinical medicine medicine Humans Missense mutation Amino Acid Metabolism Inborn Errors Molecular Biology Genetics Sanger sequencing Glutaryl-CoA Dehydrogenase Brain Diseases Metabolic Homozygote Glutaric aciduria Infant Cell Biology medicine.disease Pedigree 030104 developmental biology Inborn error of metabolism 030220 oncology & carcinogenesis Mutation (genetic algorithm) symbols Medical genetics Female |
| Zdroj: | Journal of Cellular Biochemistry. 120:3367-3372 |
| ISSN: | 1097-4644 0730-2312 |
| Popis: | Glutaric acidemia type I (GA-1) is an inborn error of metabolism due to deficiency of glutaryl-CoA dehydrogenase (GCDH), which catalyzes the conversion of glutaryl-CoA to crotonyl-CoA. GA-1 occurs in about 1 in 100 000 infants worldwide. The GCDH gene is on human chromosome 19p13.2, spans about 7 kb and comprises 11 exons and 10 introns. Tandem mass spectrometry (MS/MS) was used for clinical diagnosis in a proband from Iran with GA-1. Sanger sequencing was performed using primers specific for coding exons and exon-intron flanking regions of the GCDH gene in the proband. Cosegregation analysis and in silico assessment were performed to confirm the pathogenicity of the candidate variant. A novel homozygous missense variant c.1147C > A (p.Arg383Ser) in exon 11 of GCDH was identified. Examination of variant through in silico software tools determines its deleterious effect on protein in terms of function and stability. The variant cosegregates with the disease in family. In this study, the clinical and molecular aspects of GA-1 were investigated, which showed one novel mutation in the GCDH gene in an Iranian patient. The variant is categorized as pathogenic according to the the guideline of the American College of Medical Genetics and Genomics (ACMG) for variant interpretation. This mutation c.1147C > A (p.Arg383Ser) may also be prevalent among Iranian populations. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text