Classical and nonclassical 21-hydroxylase deficiency: A molecular study of Argentine patients
OBJECTIVE: To characterize the molecular basis of the 21-hydroxylase deficiency in a group of Argentine patients presenting the classical and nonclassical forms of the disease. DESIGN: To analyse the frequency of point mutations in the CYP21 gene by DNA amplification and mutation detection. PATIENTS...
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paper:paper_03000664_v56_n2_p239_Dain2023-06-08T15:27:13Z Classical and nonclassical 21-hydroxylase deficiency: A molecular study of Argentine patients Minutolo, Carolina Charreau, Eduardo Hernán corticotropin hydroxyprogesterone steroid 21 monooxygenase steroid hormone adrenal gland allele Argentina article chromosome analysis clinical article congenital adrenal hyperplasia controlled study enzyme deficiency female gene gene amplification gene frequency genotype phenotype correlation heterozygote hormone determination human intron male mutation rate parent point mutation prevalence priority journal salt losing nephritis sibling virilization 17-alpha-Hydroxyprogesterone Adrenal Hyperplasia, Congenital Adrenocorticotropic Hormone Alleles Argentina Female Genotype Heterozygote Homozygote Humans Male Point Mutation Steroid 21-Hydroxylase OBJECTIVE: To characterize the molecular basis of the 21-hydroxylase deficiency in a group of Argentine patients presenting the classical and nonclassical forms of the disease. DESIGN: To analyse the frequency of point mutations in the CYP21 gene by DNA amplification and mutation detection. PATIENTS: Forty-one patients from 36 nonrelated families: 25 nonclassical (NC), 11 salt-wasting (SW) and five simple virilising (SV). A total of 27 parents and 13 nonaffected siblings were also analysed. MEASUREMENTS: Basal steroid hormones and 17-hydroxyprogesterone levels following adrenal stimulation with adrenocorticotrophic hormone were measured, together with an analysis of 10 point mutations in the CYP21 gene. RESULTS: A total of 83% and 74.4% classical and non-classical chromosomes, respectively, were characterized. The intron 2 mutation was the most prevalent among classical alleles. In addition, a high frequency for R356W was observed in both groups (13.3 and 6.9%, respectively), while V281L was the most frequent mutation among the nonclassical patients with a frequency of 39.5%. No alleles containing P30L were observed, and onede novo mutation (R356W) was found. A total of 68.3% patients were fully genotyped, and all but one showed no genotype/phenotype discrepancy. Though the cut-off value for post-ACTH 17-hydroxyprogesterone stimulation was 30.25 nmol/l (10.00 μg/l), the lowest value observed in the fully genotyped nonclassical group was 42.35 nmol/l (14.00 μg/l). CONCLUSIONS: The high number of unidentified alleles in the nonclassical group suggests that less frequent mutations, or the presence of new ones, might be the cause of the disease in the Argentine population. Alternatively, the cut-off value in the ACTH-stimulated 17-hydroxyprogesterone test might overestimate the diagnosis of the nonclassical form by including some patients with heterozygous status. Fil:Minutolo, C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Charreau, E.H. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2002 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03000664_v56_n2_p239_Dain http://hdl.handle.net/20.500.12110/paper_03000664_v56_n2_p239_Dain |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
corticotropin hydroxyprogesterone steroid 21 monooxygenase steroid hormone adrenal gland allele Argentina article chromosome analysis clinical article congenital adrenal hyperplasia controlled study enzyme deficiency female gene gene amplification gene frequency genotype phenotype correlation heterozygote hormone determination human intron male mutation rate parent point mutation prevalence priority journal salt losing nephritis sibling virilization 17-alpha-Hydroxyprogesterone Adrenal Hyperplasia, Congenital Adrenocorticotropic Hormone Alleles Argentina Female Genotype Heterozygote Homozygote Humans Male Point Mutation Steroid 21-Hydroxylase |
| spellingShingle |
corticotropin hydroxyprogesterone steroid 21 monooxygenase steroid hormone adrenal gland allele Argentina article chromosome analysis clinical article congenital adrenal hyperplasia controlled study enzyme deficiency female gene gene amplification gene frequency genotype phenotype correlation heterozygote hormone determination human intron male mutation rate parent point mutation prevalence priority journal salt losing nephritis sibling virilization 17-alpha-Hydroxyprogesterone Adrenal Hyperplasia, Congenital Adrenocorticotropic Hormone Alleles Argentina Female Genotype Heterozygote Homozygote Humans Male Point Mutation Steroid 21-Hydroxylase Minutolo, Carolina Charreau, Eduardo Hernán Classical and nonclassical 21-hydroxylase deficiency: A molecular study of Argentine patients |
| topic_facet |
corticotropin hydroxyprogesterone steroid 21 monooxygenase steroid hormone adrenal gland allele Argentina article chromosome analysis clinical article congenital adrenal hyperplasia controlled study enzyme deficiency female gene gene amplification gene frequency genotype phenotype correlation heterozygote hormone determination human intron male mutation rate parent point mutation prevalence priority journal salt losing nephritis sibling virilization 17-alpha-Hydroxyprogesterone Adrenal Hyperplasia, Congenital Adrenocorticotropic Hormone Alleles Argentina Female Genotype Heterozygote Homozygote Humans Male Point Mutation Steroid 21-Hydroxylase |
| description |
OBJECTIVE: To characterize the molecular basis of the 21-hydroxylase deficiency in a group of Argentine patients presenting the classical and nonclassical forms of the disease. DESIGN: To analyse the frequency of point mutations in the CYP21 gene by DNA amplification and mutation detection. PATIENTS: Forty-one patients from 36 nonrelated families: 25 nonclassical (NC), 11 salt-wasting (SW) and five simple virilising (SV). A total of 27 parents and 13 nonaffected siblings were also analysed. MEASUREMENTS: Basal steroid hormones and 17-hydroxyprogesterone levels following adrenal stimulation with adrenocorticotrophic hormone were measured, together with an analysis of 10 point mutations in the CYP21 gene. RESULTS: A total of 83% and 74.4% classical and non-classical chromosomes, respectively, were characterized. The intron 2 mutation was the most prevalent among classical alleles. In addition, a high frequency for R356W was observed in both groups (13.3 and 6.9%, respectively), while V281L was the most frequent mutation among the nonclassical patients with a frequency of 39.5%. No alleles containing P30L were observed, and onede novo mutation (R356W) was found. A total of 68.3% patients were fully genotyped, and all but one showed no genotype/phenotype discrepancy. Though the cut-off value for post-ACTH 17-hydroxyprogesterone stimulation was 30.25 nmol/l (10.00 μg/l), the lowest value observed in the fully genotyped nonclassical group was 42.35 nmol/l (14.00 μg/l). CONCLUSIONS: The high number of unidentified alleles in the nonclassical group suggests that less frequent mutations, or the presence of new ones, might be the cause of the disease in the Argentine population. Alternatively, the cut-off value in the ACTH-stimulated 17-hydroxyprogesterone test might overestimate the diagnosis of the nonclassical form by including some patients with heterozygous status. |
| author |
Minutolo, Carolina Charreau, Eduardo Hernán |
| author_facet |
Minutolo, Carolina Charreau, Eduardo Hernán |
| author_sort |
Minutolo, Carolina |
| title |
Classical and nonclassical 21-hydroxylase deficiency: A molecular study of Argentine patients |
| title_short |
Classical and nonclassical 21-hydroxylase deficiency: A molecular study of Argentine patients |
| title_full |
Classical and nonclassical 21-hydroxylase deficiency: A molecular study of Argentine patients |
| title_fullStr |
Classical and nonclassical 21-hydroxylase deficiency: A molecular study of Argentine patients |
| title_full_unstemmed |
Classical and nonclassical 21-hydroxylase deficiency: A molecular study of Argentine patients |
| title_sort |
classical and nonclassical 21-hydroxylase deficiency: a molecular study of argentine patients |
| publishDate |
2002 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03000664_v56_n2_p239_Dain http://hdl.handle.net/20.500.12110/paper_03000664_v56_n2_p239_Dain |
| work_keys_str_mv |
AT minutolocarolina classicalandnonclassical21hydroxylasedeficiencyamolecularstudyofargentinepatients AT charreaueduardohernan classicalandnonclassical21hydroxylasedeficiencyamolecularstudyofargentinepatients |
| _version_ |
1768543468193316864 |