title: Different spectrum of mutations of isovaleryl-CoA dehydrogenase (IVD) gene in Korean patients with isovaleric acidemia.
abstract: Isovaleric acidemia (IVA) is an autosomal recessive inborn error of the leucine metabolism that is caused by a deficiency of isovaleryl-CoA dehydrogenase (IVD). Recent application of tandem mass spectrometry to newborn screening has allowed a significant expansion of the recognition of individuals with IVD deficiency. Although many patients have been reported worldwide, there are no genetically confirmed patients in Korea. This study characterizes IVD mutations in seven Korean IVA patients from six unrelated families. Bi-directional sequencing analysis identified two novel variations affecting consensus splice sites (c.144+1G>T in intron 1 and c.457-3_2CA>GG in intron 4) and three novel variations altering coding sequences (c.149G>T; Arg21Leu, c.832A>G; Ser249Gly, and c.1135T>G; Phe350Val). Five patients from four families were found to be compound heterozygotes while two unrelated patients were homozygous for the c.457-3_2CA>GG variation. Reverse-transcription polymerase chain reaction confirmed that both intron variations cause aberrant splicing. Furthermore, analysis of cultured lymphocyte extracts of the seven patients showed no detectable enzyme activity and reduced levels of IVD protein (<10.0% of control) in all samples. These results confirm IVD mutations in Korean patients with IVA and reveal that the mutation spectrum is different from previously reported patients.
authors.affiliation: Department of Laboratory Medicine and Genetics, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, Republic of Korea.
authors.forename: Yong-Wha
authors.initials: YW
authors.lastname: Lee
authors.forename: Dong Hwan
authors.initials: DH
authors.lastname: Lee
authors.forename: Jerry
authors.initials: J
authors.lastname: Vockley
authors.forename: Nam-Doo
authors.initials: ND
authors.lastname: Kim
authors.forename: You Kyoung
authors.initials: YK
authors.lastname: Lee
authors.forename: Chang-Seok
authors.initials: CS
authors.lastname: Ki
mesh_terms: D000293:Adolescent; D000592:Amino Acid Metabolism, Inborn Errors / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D015153:Blotting, Western; D002648:Child; D002675:Child, Preschool; D005260:Female; D045782:Hemiterpenes; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D050769:Isovaleryl-CoA Dehydrogenase / Q000235:genetics*; D007723:Korea; D008297:Male; D009154:Mutation / Q000235:genetics*; D015997:Neonatal Screening; D010421:Pentanoic Acids / Q000097:blood*; D016133:Polymerase Chain Reaction; D053719:Tandem Mass Spectrometry
chemical_list: D045782:Hemiterpenes; D010421:Pentanoic Acids; C008216:isovaleric acid; D050769:Isovaleryl-CoA Dehydrogenase