scholarly journals Intron 2 Splice Mutation at CYP21 Gene in Patients with Congenital Adrenal Hyperplasia in the Republic of Macedonia

2010 ◽  
Vol 13 (2) ◽  
pp. 27-33
Author(s):  
V Anastasovska ◽  
M Kocova
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Polymerase Chain Reaction Amplification ◽  
Autosomal Recessive Disorder ◽  
Splice Mutation ◽  
Adrenal Hyperplasia ◽  
Salt Wasting ◽  
Republic Of Macedonia ◽  
Cyp21 Gene ◽  
The Republic ◽  
Intron 2

Intron 2 Splice Mutation at CYP21 Gene in Patients with Congenital Adrenal Hyperplasia in the Republic of MacedoniaCongenital adrenal hyperplasia (CAH) is an autosomal recessive disorder. In 90-95% of cases it results from mutations in the gene for 21-hydroxylase (CYP21, also termed CYP21A2 and P450c21). The IVS-II-656 (C/A>G) mutation leaves ~2.0% enzyme activity, and comprises 25% of the classic CYP21 deficiency alleles and 51% of alleles in the salt-wasting form.We performed direct molecular diagnosis of the IVS-II mutation in 41 Macedonian patients with different clinical forms of CAH and 55 of their healthy parents and siblings from 37 unrelated families, using the differential polymerase chain reaction/amplification created restriction site method (PCR/ACRS). The IVS-II mutation was detected in 41.5% patients (29.3% were homozygotes and 12.2% were heterozygotes). All homozygotes had a severe classical CAH phenotype (of which 91.7% were salt-wasting and 8.3% were simple virilizing). Three of the heterozygotes had a salt-wasting (SW) phenotype and were compound heterozygotes. The IVS-II mutation was also found in 30.9% of the family members (18.2% were homozygous and 12.7% were heterozygous) and none had any clinical manifestation. The frequency of the IVS-II mutation (41.5%) in these subjects was similar to that reported elsewhere.

scholarly journals Molecular diagnosis of patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Tania Mayvel Espinosa Reyes ◽  
Teresa Collazo Mesa ◽  
Paulina Arasely Lantigua Cruz ◽  
Adriana Agramonte Machado ◽  
Emma Domínguez Alonso ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Point Mutations ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Cross Sectional ◽  
Salt Wasting ◽  
Frequent Mutations ◽  
Detection Of Mutations ◽  
21 Hydroxylase Deficiency ◽  
Intron 2

Abstract Background Congenital adrenal hyperplasia (CAH) is an autosomal recessive group of diseases. 21-Hydroxylase deficiency (21OHD) accounts for between 95 and 99% of all CAH cases. Objectives To characterize the genotype of patients clinically diagnosed with 21OHD and to identify the most frequent mutations in the Cuban population. Methods Cross-sectional descriptive study that included all patients diagnosed with 21OHD from January 2000 to December 2018. For the molecular analysis of the CYP21A2 gene, a protocol was used that used the polymerase chain reaction in 2 stages; in the first stage genomic DNA was amplified and 5 point mutations were detected in the second stage (Intron 2, Deletion of 8 bp, G318X, I172N and P30L). Results The 5 point mutations were identified in 31 of the 55 (56%) studied patients, 16/21 (76%) in the salt-wasting, 12/18 (67%) in the simple virilizing and 3/16 (19%) in the nonclassical form. The Intron 2 mutation was the most frequent, followed by G318X and 8 bp deletion. Compound heterozygotes were found in 10 patients, all corresponded to classic forms of the disease. Conclusions The causal CYP21A2 gene mutation was detected in 56% (72% in classic CAH), which makes the method encouraging. The most frequent mutations observed were Intron 2 and G318X. The detection of mutations offers confirmation of diagnosis, prediction of phenotype and genetic counseling.

The presentation of congenital adrenal hyperplasia in an unscreened population

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Tracey A. Conlon ◽  
Colin P. Hawkes ◽  
Jennifer J. Brady ◽  
Nuala P. Murphy
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Clinical Presentation ◽  
Adrenal Hyperplasia ◽  
Republic Of Ireland ◽  
Salt Wasting ◽  
Clinical Presentations ◽  
Life Threatening ◽  
History Of ◽  
The Republic ◽  
Study Inclusion

Abstract Background The aim of this study was to describe the incidence and spectrum of early clinical presentations of congenital adrenal hyperplasia (CAH) in an unscreened population. Methods A national retrospective observational study was undertaken to identify all children diagnosed with CAH in the Republic of Ireland, between January 2005 and December 2019. Reporting clinicians completed anonymized clinical questionnaires. Results There were 103 cases of CAH reported and 69 cases met the study inclusion criteria. The estimated annualized incidence of CAH in the Republic of Ireland was 1:14,754 or 0.07 cases per 1,000 live births. Forty-seven children presented clinically in the first six months of life, but only 17 of these had a confirmed diagnosis by day 10. Of these early presentations, there were 28 infants with salt-wasting, 15 females presented with virilized genitalia and four infants were detected due to a family history of CAH. Female infants presented at a median age of 0 days [IQR 0–1] and males at 14 days [IQR 9–21]. Seventy-eight percent of salt-wasting presentations occurred after day 10. Delays in clinical presentation, biochemical diagnosis and treatment initiation were identified. Conclusions The incidence of CAH is higher in Ireland than in other unscreened populations. In the absence of screening, clinicians should be aware of the possibility of CAH and appropriate investigations should be urgently requested. Life-threatening salt-wasting is the most frequent clinical presentation and many cases could be detected prior to decompensation if newborn screening were introduced.

scholarly journals Late consequences of classic congenital adrenal hyperplasia and its long-term poor control in men (case report and literature review)

2020 ◽  
Vol 16 (4) ◽  
pp. 90-102 ◽  
Author(s):  
Boris M. Shifman ◽  
Larisa K. Dzeranova ◽  
Ekaterina A. Pigarova ◽  
Anatoly N. Tiulpakov ◽  
Natalia S. Fedorova
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Autosomal Recessive Disorder ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Glucocorticoid Treatment ◽  
Salt Wasting ◽  
Adult Age ◽  
Chronic Disorder ◽  
17 Hydroxyprogesterone ◽  
21 Hydroxylase Deficiency

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) is an autosomal recessive disorder of the adrenal cortex characterized by impairment of cortisol biosynthesis (with possible impairment of aldosterone biosynthesis) and excessive pituitary ACTH release, which promotes oversecretion of intact pathways products: 17-hydroxyprogesterone (17OHP), progesterone, and adrenal androgens androstendione and testosterone. 21-hydroxylase deficiency, being the most common cause of congenital adrenal hyperplasia is a chronic disorder, that requires life-long glucocorticoid treatment, that aims both to replace cortisol and prevent ACTH-driven androgen excess. Nevertheless, reaching the optimal glucocorticoid dose is challenging because currently available glucocorticoid formulations cannot replicate the physiological circadian rhythm of cortisol secretion. The difficulties in striking the balance between uneffective normalizing of ACTH-level and excess glucocorticoid exposure leads to different abnormalities, that starts to develop at first months of life and progress, frequently gaining especial clinical meaning in adult age. In the present clinical case we introduce 35 years old male patient with salt-wasting form of 21-hydroxylase deficiency, which had either complications considered to progress due to insufficient glucocorticoid therapy, and some metabolic abnormalities, associated with supraphysiological doses of glucocorticoids.

scholarly journals Carrier Analysis and Prenatal Diagnosis of Congenital Adrenal Hyperplasia Caused by 21-Hydroxylase Deficiency in Chinese1

2000 ◽  
Vol 85 (2) ◽  
pp. 597-600
Author(s):  
Hsien-Hsiung Lee ◽  
Jing-Mei Kuo ◽  
Hsiang-Tai Chao ◽  
Yann-Jinn Lee ◽  
Jan-Gowth Chang ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Congenital Adrenal Hyperplasia ◽  
Autosomal Recessive Disorder ◽  
Single Strand Conformation Polymorphism ◽  
Severe Form ◽  
Heterozygous Mutation ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Cyp21 Gene ◽  
21 Hydroxylase Deficiency

Congenital adrenal hyperplasia (CAH) is a common autosomal recessive disorder mainly caused by defects in the steroid 21-hydroxylase (CYP21) gene. We screened 1,000 healthy people, using a previously developed differential PCR method combined with single-strand conformation polymorphism and amplification-created restriction site methods for the carrier detection of the CYP21 gene deficiency. Our results indicated that the rate of occurrence of the heterozygous CAH carrier was about 12 in 1,000, with a gene frequency of 0.0060 and an incidence frequency of 1 in 28,000 in the Chinese population. In addition, 9 cases of CAH families were performed with prenatal diagnosis. Among them, 3 cases were diagnosed as the severe form, 4 cases carried the heterozygous mutation, and 2 were normal. This is the first report of carrier frequency analysis and prenatal diagnosis of 21-hydroxylase deficiency in Chinese.

scholarly journals Szteroid-21-hidroxiláz-deficientia, a congenitalis adrenalis hyperplasia leggyakoribb oka

2018 ◽  
Vol 159 (7) ◽  
pp. 269-277
Author(s):  
Márton Doleschall ◽  
Dóra Török ◽  
Katalin Mészáros ◽  
Andrea Luczay ◽  
Zita Halász ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Clinical Care ◽  
Genetic Diseases ◽  
Autosomal Recessive Disorder ◽  
Genetic Diagnostics ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Salt Wasting ◽  
Hydroxylase Gene ◽  
21 Hydroxylase Deficiency

Abstract: Congenital adrenal hyperplasia is a group of genetic diseases due to the disablement of 7 genes; one of them is steroid 21-hydroxylase deficiency. The genes of congenital adrenal hyperplasia encode enzymes taking part in the steroidogenesis of adrenal gland. Steroid 21-hydroxylase deficiency is an autosomal recessive disorder caused by mutations of the steroid 21-hydroxylase gene. The mutations of steroid 21-hydroxylase gene cause 95% of the congenital adrenal hyperplasia cases. Although the non-classic steroid 21-hydroxylase deficiency with mild symptoms is seldom diagnosed, the classic steroid 21-hydroxylase deficiency may lead to life-threatening salt-wasting and adrenal crises due to the insufficient aldosterone and cortisol serum levels. The classic type requires life-long steroid replacement which may result in cushingoid side effects, and typical comorbidities may be also developed. The patients’ quality of life is decreased, and their mortality is much higher than that of the population without steroid 21-hydroxylase deficiency. The diagnosis, consequences and the patients’ life-long clinical care require a multidisciplinary approach: the specialists in pediatrics, internal medicine, endocrinology, laboratory medicine, genetic diagnostics, surgery, obstetrics-gynecology and psychology need to work together. Orv Hetil. 2018; 159(7): 269–277.

scholarly journals Concurrence of Meningomyelocele and Salt-Wasting Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency

2015 ◽  
Vol 2015 ◽  
pp. 1-4
Author(s):  
Heves Kırmızıbekmez ◽  
Rahime Gül Yesiltepe Mutlu ◽  
Serdar Moralıoğlu ◽  
Ahmet Tellioğlu ◽  
Ayşenur Cerrah Celayir
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Growth Retardation ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Salt Wasting ◽  
Significant Regression ◽  
One Year ◽  
The One ◽  
21 Hydroxylase Deficiency

Congenital adrenal hyperplasia (CAH) is a group of inherited defects of cortisol biosynthesis. A case of classical CAH due to 21-hydroxylase deficiency (21-OHD) with early onset of salt waste and concurrence of meningomyelocele (MMC) was presented here. The management of salt-wasting crisis which is complicated by a postrenal dysfunction due to neurogenic bladder was described. Possible reasons of growth retardation in the one-year follow-up period were discussed. A significant regression of the phallus with proper medical treatment was also mentioned.

Aldosterone Synthesis in Salt-Wasting Congenital Adrenal Hyperplasia with Complete Absence of Adrenal 21-Hydroxylase

1991 ◽  
Vol 324 (3) ◽  
pp. 145-149 ◽  
Author(s):  
Phyllis W. Speiser ◽  
Levon Agdere ◽  
Hajime Ueshiba ◽  
Perrin C. White ◽  
Maria I. New
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Adrenal Hyperplasia ◽  
Salt Wasting

scholarly journals The role of imaging in congenital adrenal hyperplasia

2014 ◽  
Vol 58 (7) ◽  
pp. 701-708 ◽  
Author(s):  
Sara Reis Teixeira ◽  
Paula Condé Lamparelli Elias ◽  
Marco Túlio Soares Andrade ◽  
Andrea Farias Melo ◽  
Jorge Elias Junior
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Adrenal Tumors ◽  
Adrenal Hyperplasia ◽  
Salt Wasting ◽  
Testicular Adrenal Rest Tumors ◽  
High Incidence ◽  
Adrenal Rest ◽  
Hormonal Evaluation

Congenital adrenal hyperplasia (CAH) is an autossomic recessive disorder caused by impaired steroidogenesis. Patients with CAH may present adrenal insufficiency with or without salt-wasting, as well as various degrees of virilization and fertility impairment, carrying a high incidence of testicular adrenal rest tumors and increased incidence of adrenal tumors. The diagnosis of CAH is made based on the adrenocortical profile hormonal evaluation and genotyping, in selected cases. Follow-up is mainly based on hormonal and clinical evaluation. Utility of imaging in this clinical setting may be helpful for the diagnosis, management, and follow-up of the patients, although recommendations according to most guidelines are weak when present. Thus, the authors aimed to conduct a narrative synthesis of how imaging can help in the management of patients with CAH, especially focused on genitography, ultrasonography, computed tomography, and magnetic resonance imaging.

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