title: Analysis of the steroidogenic acute regulatory protein (StAR) gene in Japanese patients with congenital lipoid adrenal hyperplasia.
abstract: Genomic DNA from 19 Japanese patients with congenital lipoid adrenal hyperplasia (lipoid CAH) representing 16 different families was examined to identify the genetic alterations of steroidogenic acute regulatory protein (StAR). Ten of 19 patients had a 46,XX karyotype and nine had a 46,XY karyotype. Six of the 46,XX patients have experienced spontaneous pubertal changes including breast development and irregular menstruation whereas none of the 46,XY subjects displayed pubertal changes. Eight different mutations were identified. Sixteen patients were either homozygotes or compound heterozygotes for the Q258X mutation. The seven other mutations identified were 189delG, 246insG, 564del13bp, 838delA, Q212X, A218V and M225T. The 189delG, 246insG, 546del13bp and Q212X mutants encode truncated proteins. COS-1 cells transfected with expression vectors encoding cDNAs for the mutant StAR proteins which affect the C-terminus, 838delA, A218V and Q258X, exhibited no steroidogenesis enhancing activity. However, the M225T mutant retained some steroidogenic activity. The patient with the M225T mutation had late onset of this disorder and some capacity to secrete testosterone in response to hCG. These findings suggest: (i) that the Q258X mutation can be used as a genetic marker for the screening of Japanese for lipoid CAH, (ii) that the C-terminus of StAR plays an important role in the protein's activity and (iii) that there are differences in the extent of functional impairment of the testis and ovaries in lipoid CAH.
authors.affiliation: Department of Pediatrics, Hokkaido University School of Medicine, Sapporo, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Nakae
authors.forename: T
authors.initials: T
authors.lastname: Tajima
authors.forename: T
authors.initials: T
authors.lastname: Sugawara
authors.forename: F
authors.initials: F
authors.lastname: Arakane
authors.forename: K
authors.initials: K
authors.lastname: Hanaki
authors.forename: T
authors.initials: T
authors.lastname: Hotsubo
authors.forename: N
authors.initials: N
authors.lastname: Igarashi
authors.forename: Y
authors.initials: Y
authors.lastname: Igarashi
authors.forename: T
authors.initials: T
authors.lastname: Ishii
authors.forename: N
authors.initials: N
authors.lastname: Koda
authors.forename: T
authors.initials: T
authors.lastname: Kondo
authors.forename: H
authors.initials: H
authors.lastname: Kohno
authors.forename: Y
authors.initials: Y
authors.lastname: Nakagawa
authors.forename: K
authors.initials: K
authors.lastname: Tachibana
authors.forename: Y
authors.initials: Y
authors.lastname: Takeshima
authors.forename: K
authors.initials: K
authors.lastname: Tsubouchi
authors.forename: J F
authors.initials: JF
authors.lastname: Strauss
authors.forename: K
authors.initials: K
authors.lastname: Fujieda
mesh_terms: D000312:Adrenal Hyperplasia, Congenital / Q000235:genetics*; D000818:Animals; D019556:COS Cells; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D015870:Gene Expression / Q000235:genetics; D005808:Genes, Recessive; D005819:Genetic Markers / Q000235:genetics; D007564:Japan; D007621:Karyotyping; D008297:Male; D009154:Mutation; D010750:Phosphoproteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011284:Pregnenolone / Q000096:biosynthesis; D017384:Sequence Deletion; D013739:Testosterone / Q000378:metabolism; D014162:Transfection / Q000235:genetics; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D006063:Chorionic Gonadotropin; D005819:Genetic Markers; D010750:Phosphoproteins; D000098682:Steroidogenic Acute Regulatory Protein; D013739:Testosterone; D011284:Pregnenolone