title: A novel homozygous mutation of the nicotinamide nucleotide transhydrogenase gene in a Japanese patient with familial glucocorticoid deficiency.
abstract: Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disorder characterized by primary hypocortisolism and normal mineralocorticoid production. Recently, NNT encoding the nicotinamide nucleotide transhydrogenase has been identified as a causative gene for FGD. Thus, we examined NNT in six Japanese FGD patients with no recognizable mutation in the previously known four responsible genes for FGD (MC2R, MRAP, STAR, and MCM4), and identified a novel homozygous substitution (c.644T>C; p.Phe215Ser) in a single 17.5-year-old boy. His parents were heterozygous for this mutation. This substitution was absent from 120 Japanese control subjects and was not registered in public databases including JSNP Database. The phenylalanine residue at the 215th codon was evolutionally conserved, and the p.Phe215Ser was assessed to be a pathologic mutation by in silico protein function analyses. The results, in conjunction with the previous data, imply that NNT mutations account for 5-10% of FGD patients, and that underlying factor(s) still remains to be clarified in a substantial fraction of FGD patients.
authors.affiliation: Department of Pediatrics, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Yamaguchi
authors.forename: Fumiko
authors.initials: F
authors.lastname: Kato
authors.forename: Tomonobu
authors.initials: T
authors.lastname: Hasegawa
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Katsumata
authors.forename: Maki
authors.initials: M
authors.lastname: Fukami
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Matsui
authors.forename: Keisuke
authors.initials: K
authors.lastname: Nagasaki
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Ogata
mesh_terms: D000293:Adolescent; D000309:Adrenal Insufficiency / Q000235:genetics*; D044466:Asian People; D004252:DNA Mutational Analysis; D005938:Glucocorticoids / Q000172:deficiency*; D006720:Homozygote; D006801:Humans; D008297:Male; D020125:Mutation, Missense / Q000502:physiology; D009250:NADP Transhydrogenases / Q000235:genetics*
chemical_list: D005938:Glucocorticoids; D009250:NADP Transhydrogenases