Identification of three missense mutations in the peroxisome proliferator-activated receptor alpha gene in Japanese subjects with maturity-onset diabetes of the young

We screened the protein-coding region of the peroxisome proliferator-activa ted receptor alpha gene (PPARA) and the flanking intron sequences for mutat ions in 57 unrelated Japanese subjects with maturity-onset diabetes of the young (MODY). We found three missense mutations, designated P22R, D140Y, an d V227A. The D140Y and V227A mutations were found at similar frequencies in MODY and in nondiabetic Japanese subjects, suggesting that they were unlik ely to be pathogenic. The P22R mutation was found in a single female subjec t with MODY. Two of her four siblings, all of whom were diagnosed with diab etes before age 35 years. also inherited the P22R mutation. However, two ot her diabetic siblings had not inherited the mutant allele, implying that th e 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.