Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 2 de 2
Filter
Add filters








Language
Year range
1.
Braz. j. med. biol. res ; 38(1): 17-25, Jan. 2005. tab
Article in English | LILACS | ID: lil-405545

ABSTRACT

The WT1 transcription factor regulates SRY expression during the initial steps of the sex determination process in humans, activating a gene cascade leading to testis differentiation. In addition to causing Wilms' tumor, mutations in WT1 are often responsible for urogenital defects in men, while SRY mutations are mainly related to 46,XY pure gonadal dysgenesis. In order to evaluate their role in abnormal testicular organogenesis, we screened for SRY and WT1 gene mutations in 10 children with XY partial gonadal dysgenesis, 2 of whom with a history of Wilms' tumor. The open reading frame and 360 bp of the 5' flanking sequence of the SRY gene, and the ten exons and intron boundaries of the WT1 gene were amplified by PCR of genomic DNA. Single-strand conformation polymorphism was initially used for WT1 mutation screening. Since shifts in fragment migration were only observed for intron/exon 4, the ten WT1 exons from all patients were sequenced manually. No mutations were detected in the SRY 5' untranslated region or within SRY open-reading frame sequences. WT1 sequencing revealed one missense mutation (D396N) in the ninth exon of a patient who also had Wilms' tumor. In addition, two silent point mutations were found in the first exon including one described here for the first time. Some non-coding sequence variations were detected, representing one new (IVS4+85A>G) and two already described (-7ATG T>G, IVS9-49 T>C) single nucleotide polymorphisms. Therefore, mutations in two major genes required for gonadal development, SRY and WT1, are not responsible for XY partial gonadal dysgenesis.


Subject(s)
Humans , Male , Infant , Child, Preschool , Child , DNA-Binding Proteins/genetics , Genes, Wilms Tumor , /genetics , Mutation/genetics , Testis/embryology , /genetics , Base Sequence , Exons , Molecular Sequence Data , Open Reading Frames/genetics , Phenotype , Polymerase Chain Reaction
2.
Braz. j. med. biol. res ; 29(1): 1-13, Jan. 1996. ilus, tab
Article in English | LILACS | ID: lil-161646

ABSTRACT

The most common enzymatic defect of steroid synthesis is deficiency of the adrenal steroid 21-hydroxylase. Inhibition of the formation of cortisol results in an increased pituitary release of ACTH which in turn drives the adrenal cortex to overproduce androgens. This hormonal setting affects the development of genetic females by misdirecting the differentiation of external genitalia towards the male type. Since the isolation of the gene encoding 21-hydroxylase enzyme in 1984, gene deletions, large gene conversions, and microconversions have been reported to be responsible for the disease. In this paper, we report a study of this genetic defect in 22 families with one or more affected offspring diagnosed as having the classical form of congenital adrenal hyperplasia. The DNA from 30 patients was analyzed with three restriction enzymes. Hybridization with a 21-hydroxylase cDNA probe and the 5' end of a C4 genomic probe disclosed gene deletion in 7.3 percent (3/41) of the disease-related chromosomes. The rate of large gene conversion was 17.1 percent (7/41), and no abnormality in the hybridization pattern was observed in 75.6 percent (31/41) of the disease alleles. Densitometry of the autoradiographs was used to determine the ratio of the copy-number of the 2 1-hydroxylase gene (CYP21B) to the copy-number of its pseudogene (CYP21A). Differences in phenotype, the low frequency of gene deletion, and the high frequency of gene conversion compared with other studies in different populations indicated that 21-hydroxylase deficiency in the Brazilian population may involve different molecular mutations.


Subject(s)
Humans , Male , Female , Infant, Newborn , Infant , Child, Preschool , Adrenal Hyperplasia, Congenital/genetics , Aldosterone/biosynthesis , Gene Deletion , Hydrocortisone/blood , Mutation/genetics , Steroid 21-Hydroxylase/deficiency , Androgens/blood , Blotting, Southern , Brazil , Sex Characteristics , Gene Frequency , Steroid 21-Hydroxylase/biosynthesis , Steroid 21-Hydroxylase/genetics
SELECTION OF CITATIONS
SEARCH DETAIL