2 3 オヨビ 3 3 シグマトロピー テンイ ノ リッタイ カガクテキ ケンキュウ

京都大学0048新制・論文博士農学博士乙第3613号論農博第755号新制||農||258(附属図書館)学位論文||S53||N1020(農学部図書室)UT51-53-C304(主査)教授 井上 雄三, 教授 中島 稔, 教授 小清水 弘一学位規則第5条第2項該当Kyoto UniversityDFA

Contribution of two missense mutations (G71R and Y486D) of the bilirubin UDP glycosyltransferase (UGT1A1) gene to phenotypes of Gilbert's syndrome and Crigler–Najjar syndrome type II

AbstractIn our mutation analyses of bilirubin UDP glycosyltransferase (UGT1A1) gene, we encountered six patients with Crigler–Najjar syndrome type II who were double homozygotes for G71R and Y486D, a patient with Gilbert's syndrome who was a single homozygote for G71R and six patients with Gilbert's syndrome who were single heterozygote for G71R. To clarify the role of each mutation in the occurrence of the two syndromes, we made four mutant expression models. Relative UGT1A1 activity of a single homozygous model of G71R was 32.2±1.6% of normal, that of a single homozygous model of Y486D was 7.6±0.5%, that of a double homozygous model of G71R and Y486D was 6.2±1.6% and that of a heterozygous model of G71R was 60.2±3.5%. The decreased activities of the single homozygous model of G71R and the double homozygous model were at an appropriate level to be diagnosed as Gilbert's syndrome and CN-II, respectively. The activity of a single heterozygous model of G71R was somewhat high to develop to the phenotype of Gilbert's syndrome, suggesting the presence of additional factors for the etiology of Gilbert's syndrome