Classical and nonclassical 21‐hydroxylase deficiency: a molecular study of Argentine patients

Daín, Liliana; Buzzalino, Noemí; Oneto, Adriana; Belli, Susana; Stivel, Mirta; Pasqualini, Titania; Minutolo, Carolina; Charreau, Eduardo H.; Alba, Liliana

doi:10.1046/j.0300-0664.2001.01419.x

Cited by 27 publications

(30 citation statements)

References 38 publications

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“…These differences were due mainly to the high frequencies of the Q318X and 1760_1761insT mutations found in these patients from the Amazon region. On the other hand, our data are comparable to those found in Argentine patients (Dain et al, 2002). When the null and A group (IVS2-13A/C > G, predominantly) mutations are grouped together, the prevalence of mutations commonly associated to the SW and SV forms corresponds to 64% of the total in our patient sample, a value that is higher than those found in most of the previously studied populations, except in Japanese (64%-67%) and Mexican (62%) patients.…”

Section: Discussionsupporting

confidence: 78%

“…In North Europe, the most frequent mutation in NC alleles is P30L (Table 2). (1) 43 (1) 20 (1) 102 (1) This mutation is also common in Argentine patients (25%) (Dain et al, 2002). Mutation Q318X, the second most common mutation in our patient sample along with mutation V281L (frequency of 12%), is a severe mutation (null group) that abolishes the activity of the 21-OH enzyme.…”

Section: Discussionmentioning

confidence: 99%

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CYP21 gene mutations in Brazilian patients with 21-hydroxylase deficiency from the Amazon region

et al. 2008

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Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (P450c21, CYP21) accounts for about 95% of all CAH cases. The incidence of CYP21 gene mutations has been extensively studied in the last years, but in Brazil it has been investigated only in Southeast Brazilian patients. This study is the first report on the distribution of CYP21 mutations in patients from the Amazon region. Direct sequencing of the CYP21 gene identified at least one mutation in 96% of the studied chromosomes. The most common mutations found were IVS2-13A/C > G (36%), Q318X (12%), V281L (12%), 1760_1761insT (9%), Cluster E6 (7%), and P30L (7%). The worldwide most common mutations were identified among patients from the Amazon region at frequencies that may be expected for a population resulting from the admixture of Europeans (predominantly Portuguese), African Blacks and Amerindians, in proportions that differ from those estimated for South Brazilian populations. Interethnic mixture may explain the differences in the frequencies of some mutations between Brazilian patients from the Amazon and from the Southeast of the country. However, the differences found may also be due to variation in the number of patients with the different clinical forms of 21-hydroxylase deficiency in the studies carried out so far.

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Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

CYP21 gene mutations in Brazilian patients with 21-hydroxylase deficiency from the Amazon region

et al. 2008

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“…DNA was isolated from peripheral blood leukocytes from 309 patients (74 classical, 235 NCCAH) and the 10 most frequent pseudogene-derived point mutations in the CYP21A2 gene were screened [11]. In 66 samples (7 classical, 59 NCCAH) with at least one non-determined allele, presence of novel or less frequent disease-causing mutations was further analyzed by direct sequencing as previously described [8].…”

Section: Methodsmentioning

confidence: 99%

“…Patients were included following the diagnostic criteria already described [11,12]. Details on clinical manifestations in patients carrying the novel transition are presented in Online Resource 1.…”

Section: Methodsmentioning

confidence: 99%

Misregulation effect of a novel allelic variant in the Z promoter region found in cis with the CYP21A2 p.P482S mutation: implications for 21-hydroxylase deficiency

et al. 2015

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The aim of the current study was to search for the presence of genetic variants in the CYP21A2 Z promoter regulatory region in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Screening of the 10 most frequent pseudogene-derived mutations was followed by direct sequencing of the entire coding sequence, the proximal promoter, and a distal regulatory region in DNA samples from patients with at least one non-determined allele. We report three non-classical patients that presented a novel genetic variant-g.15626A>G-within the Z promoter regulatory region. In all the patients, the novel variant was found in cis with the mild, less frequent, p.P482S mutation located in the exon 10 of the CYP21A2 gene. The putative pathogenic implication of the novel variant was assessed by in silico analyses and in vitro assays. Topological analyses showed differences in the curvature and bendability of the DNA region bearing the novel variant. By performing functional studies, a significantly decreased activity of a reporter gene placed downstream from the regulatory region was found by the G transition. Our results may suggest that the activity of an allele bearing the p.P482S mutation may be influenced by the misregulated CYP21A2 transcriptional activity exerted by the Z promoter A>G variation.

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“…However, much scientific attention has focused on genotype to phenotype relationships in classical and non-classical 21OHD and possible prediction of the course of the disorder [2,3,4,5]. …”

Section: Introductionmentioning

confidence: 99%

Two Brothers with Non-Classical 21-Hydroxylase Deficiency: To Treat or Not to Treat?

et al. 2004

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Variations in phenotype in 21-hydroxylase deficiency (21OHD) have cautioned against initiating treatment in the absence of abnormal clinical features. We report 2 Caucasian brothers with compound heterozygous mutations of the CYP21 gene and mild clinical and biochemical features of late-presenting 21OHD. The index case presented aged 8.5 years with mild genital virilization and bone age advanced by 5 years. Elevated basal and synacthen-stimulated 17-hydroxyprogesterone (17OHP; 22.4 and 246 nmol/l) and androstenedione (10.9 and 19.9 nmol/l) levels confirmed 21OHD. His younger brother was investigated at age 7.3 years, and although examination showed normal pre-pubertal genitalia, basal and synacthen-stimulated 17OHP (32.4 and 281 nmol/l) and androstenedione (6.2 and 9.0 nmol/l) were abnormal, and bone age was advanced by 1.5 years. Because of actual or incipient virilization, both patients were treated with glucocorticoid replacement 8–12 mg/m²/day. This decision is discussed in the context of published guidelines for the management of 21OHD.

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Classical and nonclassical 21‐hydroxylase deficiency: a molecular study of Argentine patients

Cited by 27 publications

References 38 publications

CYP21 gene mutations in Brazilian patients with 21-hydroxylase deficiency from the Amazon region

CYP21 gene mutations in Brazilian patients with 21-hydroxylase deficiency from the Amazon region

Misregulation effect of a novel allelic variant in the Z promoter region found in cis with the CYP21A2 p.P482S mutation: implications for 21-hydroxylase deficiency

Two Brothers with Non-Classical 21-Hydroxylase Deficiency: To Treat or Not to Treat?

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