title: Screening of SLC25A13 mutations in early and late onset patients with citrin deficiency and in the Japanese population: Identification of two novel mutations and establishment of multiple DNA diagnosis methods for nine mutations.
abstract: We have recently identified SLC25A13 on chromosome 7q21.3 as the gene responsible for adult-onset type II citrullinemia (CTLN2) and found seven mutations in the SLC25A13 gene of CTLN2 patients. Most recently, the SLC25A13 mutations have been detected in neonatal/infantile patients with a type of neonatal hepatitis associated with cholestasis (NICCD). In the present study, we identified a novel mutation, E601X, in the SLC25A13 gene and established multiple DNA diagnosis methods for eight mutations by using a genetic analyzer with GeneScan and the single primer extension procedure (SNaPshot). An additional novel missense mutation (variation), E601K, was detected by SNaPshot analysis and was indistinguishable from the mutation E601X detected by the PCR/RFLP method. Multiple DNA diagnoses for the nine mutations revealed that 100 (male/female: 70/30) out of 115 CTLN2 and 38 (14/24) out of 45 NICCD patients tested were homozygotes or compound heterozygotes. The frequency of homozygotes carrying SLC25A13 mutations in both alleles is estimated to be minimally 1 in 21,000 from carrier detection (18 in 1,315 individuals tested) in the Japanese population. The differences in the gender ratio and in mutation types between CTLN2 and NICCD patients are significant. It is, however, unknown whether all homozygotes with mutated SLC25A13 in both alleles suffer from NICCD, CTLN2, both, or neither.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Kagoshima University, Kagoshima, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Yamaguchi
authors.forename: Keiko
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Tomotsugu
authors.initials: T
authors.lastname: Yasuda
authors.forename: Ikumi
authors.initials: I
authors.lastname: Nishi
authors.forename: Mikio
authors.initials: M
authors.lastname: Iijima
authors.forename: Masanori
authors.initials: M
authors.lastname: Nakagawa
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Osame
authors.forename: Ikuko
authors.initials: I
authors.lastname: Kondo
authors.forename: Takeyori
authors.initials: T
authors.lastname: Saheki
mesh_terms: D017668:Age of Onset; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002135:Calcium-Binding Proteins / Q000172:deficiency / Q000235:genetics*; D002779:Cholestasis / Q000150:complications / Q000151:congenital / Q000175:diagnosis / Q000235:genetics*; D020159:Citrullinemia / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D018389:Codon, Nonsense / Q000235:genetics; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005820:Genetic Testing / Q000379:methods*; D005838:Genotype; D006505:Hepatitis / Q000150:complications / Q000151:congenital / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D007564:Japan / Q000453:epidemiology; D008297:Male; D026901:Membrane Transport Proteins; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length
chemical_list: D002135:Calcium-Binding Proteins; D018389:Codon, Nonsense; D026901:Membrane Transport Proteins; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins; C119629:SLC25A13 protein, human