title: Phenotypic and genotypic spectrum of Turkish patients with isovaleric acidemia.
abstract: We aim to investigate the genetic basis of isovaleryl-CoA dehydrogenase (IVD) gene mutations and genotype-phenotype correlations in Turkish patients. Accordingly, bi-directional sequencing was performed to screen 26 patients with isovaleric acidemia (IVA). Nine novels (c.145delC, c.234 + 3G > C, c.506_507insT, p.Glu85Gln, p.Met147Val, p.Ala268Val, p.Ile287Met, p.Gly346Asp and p.Arg382Trp) and six previously reported (c.456 + 2T > C, p.Arg21His, p.Arg21Pro, p.Arg363Cys, p.Arg363His p.Glu379Lys) pathogenic mutations were identified. Pathogenicity of the novel mutations was supported using computational programs. No clear genotype-phenotype correlation could be determined. One of the cases with the novel c.234 + 3G > C mutation has portoseptal liver fibrosis, the clinical condition that was first reported for IVA. This study is the first comprehensive report from Turkey related to IVA genetics that provides information about the high number of disease-causing novel mutations.
authors.affiliation: Hacettepe University, Faculty of Medicine, Department of Pediatrics, Metabolism Unit, Ankara, Turkey; Hacettepe University, Institute of Child Health, Ankara, Turkey.
authors.forename: Rıza Koksal
authors.initials: RK
authors.lastname: Ozgul
authors.affiliation: Aksaray University, Faculty of Science and Arts, Department of Biology, Aksaray, Turkey.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Karaca
authors.affiliation: Dr. Sami Ulus Maternity and Children Hospital, Training and Research Hospital, Division of Metabolism, Ankara, Turkey.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Kilic
authors.affiliation: Public Health Organisation of Turkey, Ankara, Turkey.
authors.forename: Ozgul
authors.initials: O
authors.lastname: Kucuk
authors.affiliation: Hacettepe University, Faculty of Medicine, Department of Pediatrics, Metabolism Unit, Ankara, Turkey.
authors.forename: Didem
authors.initials: D
authors.lastname: Yucel-Yilmaz
authors.affiliation: Hacettepe University, Faculty of Medicine, Department of Pediatrics, Metabolism Unit, Ankara, Turkey.
authors.forename: Ozlem
authors.initials: O
authors.lastname: Unal
authors.affiliation: Hacettepe University, Faculty of Medicine, Department of Pediatrics, Metabolism Unit, Ankara, Turkey.
authors.forename: Burcu
authors.initials: B
authors.lastname: Hismi
authors.affiliation: Department of Pediatrics, Kirikkale University, Kirikkale, Turkey.
authors.forename: Didem
authors.initials: D
authors.lastname: Aliefendioglu
authors.affiliation: Hacettepe University, Faculty of Medicine, Department of Pediatrics, Metabolism Unit, Ankara, Turkey.
authors.forename: Serap
authors.initials: S
authors.lastname: Sivri
authors.affiliation: Hacettepe University, Faculty of Medicine, Department of Pediatrics, Metabolism Unit, Ankara, Turkey.
authors.forename: Aysegul
authors.initials: A
authors.lastname: Tokatli
authors.affiliation: Hacettepe University, Faculty of Medicine, Department of Pediatrics, Metabolism Unit, Ankara, Turkey.
authors.forename: Turgay
authors.initials: T
authors.lastname: Coskun
authors.affiliation: Hacettepe University, Faculty of Medicine, Department of Pediatrics, Metabolism Unit, Ankara, Turkey. Electronic address: adursun@hacettepe.edu.tr.
authors.forename: Ali
authors.initials: A
authors.lastname: Dursun
mesh_terms: D000293:Adolescent; D000328:Adult; D000592:Amino Acid Metabolism, Inborn Errors / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003241:Consanguinity; D005260:Female; D018740:Genetic Heterogeneity; D005838:Genotype; D006801:Humans; D007223:Infant; D050769:Isovaleryl-CoA Dehydrogenase / Q000172:deficiency* / Q000235:genetics; D008297:Male; D009154:Mutation; D010641:Phenotype; D012326:RNA Splicing; D014421:Turkey; D055815:Young Adult
chemical_list: D050769:Isovaleryl-CoA Dehydrogenase
keywords: Genotype–phenotype correlation; IVD gene; Isovaleric acidemia; Mutation screening