title: Identification of three missense mutations in the peroxisome proliferator-activated receptor alpha gene in Japanese subjects with maturity-onset diabetes of the young.
abstract: We screened the protein-coding region of the peroxisome proliferator-activated receptor alpha gene (PPARA) and the flanking intron sequences for mutations in 57 unrelated Japanese subjects with maturity-onset diabetes of the young (MODY). We found three missense mutations, designated P22R, D140Y, and V227A. The D140Y and V227A mutations were found at similar frequencies in MODY and in nondiabetic Japanese subjects, suggesting that they were unlikely to be pathogenic. The P22R mutation was found in a single female subject with MODY. Two of her four siblings, all of whom were diagnosed with diabetes before age 35 years, also inherited the P22R mutation. However, two other diabetic siblings had not inherited the mutant allele, implying that the P22R mutation was not the cause of MODY in this family. Variation in the coding region of PPARA is unlikely to be a major cause of MODY in Japanese people.
authors.affiliation: Howard Hughes Medical Institute, The University of Chicago, IL 60637, USA. mhara@midway.uchicago.edu
authors.forename: M
authors.initials: M
authors.lastname: Hara
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.forename: V P
authors.initials: VP
authors.lastname: Paz
authors.forename: N
authors.initials: N
authors.lastname: Iwasaki
authors.forename: M
authors.initials: M
authors.lastname: Honda
authors.forename: Y
authors.initials: Y
authors.lastname: Iwamoto
authors.forename: G I
authors.initials: GI
authors.lastname: Bell
mesh_terms: D000328:Adult; D017668:Age of Onset; D000483:Alleles; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D005820:Genetic Testing; D014644:Genetic Variation; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D020125:Mutation, Missense; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors