Different Gene Defects in the Salt‐Wasting (SW), Simple Virilizing (SV), and Nonclassical (NC) Types of Congenital Adrenal Hyperplasia (CAH)

Knorr, Dietrich; Albert, E. D.; Bidlingmaier, F.; Holler, W.; Scholz, Siegfried

doi:10.1111/j.1749-6632.1985.tb14592.x

Cited by 8 publications

(6 citation statements)

References 12 publications

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“…In the small group of patients with SV CAH (n = 8), there was no significant distortion of frequency of any antigen. The previously noted increases in A2, B5(51) (Knorr et al, 1985) were not significant in this study.…”

Section: Resultscontrasting

confidence: 87%

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Hla Associations in Patients With Polycystic Ovaries and in Patients With Congenital Adrenal Hyperplasia Caused by 21‐hydroxylase Deficiency

Hague

Adams

Algar

et al. 1990

Clinical Endocrinology

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Ninety-nine Caucasian patients with ultrasonically detected polycystic ovaries (PCO) were typed for human leucocyte (HLA) antigens. Fifty patients with congenital adrenal hyperplasia (CAH) caused by 21-hydroxylase deficiency were similarly typed. Among the patients with PCO, there was a significant increase in the frequency of HLA DRW6 (P = 0.0027) compared with that found in a control population, which remained significant (P = 0.027) when corrected for the number of antigens tested. This difference was reduced, but remained significant (P = 0.006), when the patients with CAH and PCO were added. There was also a significant decrease in the frequency of HLA DR7 (P = 0.017) among the patients with PCO compared with a control population, but there was no distortion of the frequencies of HLA A, B or Cw antigens. Among the patients with CAH, previously well documented associations of HLA B14 and DR1 with non-classical disease were confirmed. The frequency of HLA Bw47 was increased among the whole group of CAH patients (P = 0.05) but was not increased among those with classical salt-wasting (SW) or simple virilizing (SV) disease. Family studies were performed in close female relatives of 16 of the PCO patients and 21 of the CAH patients but no evidence for genetic linkage between HLA and PCO status could be found. These data suggest that there is no significant component of disturbed adrenal steroid 21-hydroxylase activity to account for the PCO morphology, although there may be some other genetic factor, more proximal to the centromere on chromosome 6, affecting the development of polycystic ovaries.

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Section: Resultscontrasting

confidence: 87%

“…In the combined CAH group (n = 50), there were highly significant increases in B14 (P=0-0033) and DRI (P=0.039) with a non-significant increase in Aw33, confirming the well recognized excess of these antigens in the late-onset group (Knorr et al, 1985). The frequency of Bw47 was increased (6.0% us 0.6%; P=0*050).…”

Section: Resultsmentioning

confidence: 73%

Hla Associations in Patients With Polycystic Ovaries and in Patients With Congenital Adrenal Hyperplasia Caused by 21‐hydroxylase Deficiency

Hague

Adams

Algar

et al. 1990

Clinical Endocrinology

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“…The first genetic analyses have been performed by linkage analysis of HLA haplotypes, with patients in the same family being HLAidentical. Furthermore, associations of disease-causing alleles to certain HLA alleles have been observed [32]. Direct genetic analysis of CYP21A2 is complicated by the fact that the functional gene and a non-functional pseudogene (CYP21A1P) are located closely adjacent in tandem arrangement with the C4A and C4B genes encoding for the fourth component of the serum complement [33].…”

Section: Advances In Genetic Diagnosticsmentioning

confidence: 99%

Recent advances in diagnosis, treatment, and outcome of congenital adrenal hyperplasia due to 21-hydroxylase deficiency

Riepe

Sippell

2007

Rev Endocr Metab Disord

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Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) is an autosomal-recessive disease causing cortisol deficiency, aldosterone deficiency and hyperandrogenism. Diagnosis of 21-OHD is confirmed by steroid analysis in newborn screening or later on. Standard medical treatment consists of oral glucocorticoid and mineralocorticoid administration in order to suppress adrenal androgens and to compensate for adrenal steroid deficiencies. However, available treatment is far from ideal, and not much is known about the long-term outcome in CAH as trials in patients in adulthood or old age are rare. Here we briefly describe the pathophysiology, clinical picture, genetics and epidemiology of 21-OHD. This is followed by a comprehensive review of the recent advances in diagnosis, treatment and outcome. Novel insights have been gained in the fields of newborn screening, specific steroid measurement utilizing mass spectrometry, genetics, glucocorticoid stress dosing, additive medical therapy, prenatal treatment, side-effects of medical treatment, adrenomedullary involvement, metabolic morbidity, fertility and gender identity. However, many issues are still unresolved, and novel questions, which will have to be answered in the future, arise with every new finding.

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“…The clarification of the genetic background of CAH has been influential in the diagnosis and the classification of the disease (6, 7). Currently, the disorder is classified into the classic or non-classic (NC late onset) CAH form, respectively (8, 9). The classic form is further divided into the simple virilising (SV) form (~25% of individuals) and the salt-wasting (SW) form, in which aldosterone production is inadequate (≥75% of individuals).…”

Section: Introductionmentioning

confidence: 99%

Genotype Is Associated to the Degree of Virilization in Patients With Classic Congenital Adrenal Hyperplasia

et al. 2018

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Background: Molecular defects of CYP21A2 consistently decrease 21-hydroxylase activity and result in a variable expression of disease severity in patients with congenital adrenal hyperplasia (CAH).Aim: The genotype and biochemical findings were examined in an attempt to reveal any association to the degree of virilization in classic CAH patients.Methods: The study included 18 CAH patients with complete characterization of CYP21A2 mutations and were sorted based on the severity of the inherited mutations and the expected percentage of 21-hydroxylase enzyme activity.Results: Eleven out of the 18 patients manifested the SW form with the remaining seven exhibiting the SV form. The most frequent genetic defect in the classic salt-wasting (SW) and simple virilising (SV) forms was the IVS2-13A/C>G (36.1%) mutation, followed by delEX1-3 (19.4%) and p.Ile172Asn (19.4%). Four patients, who shared a combination of two mutations belonging to the most severe type, manifested only the SW form. Four out of five patients who shared homozygosity in the IVS2-13A/C>G mutation, demonstrated the SW form and only one demonstrated the SV form. All four patients who shared the p.Ile172Asn mutation, either in the homozygous or compound heterozygous state, manifested the SV form. Interestingly, a female neonate with SW, bearing the IVS2-13A/C>G/Large del, exhibited complete male virilisation (Prader 5). The remaining four affected female new-borns also exhibited the SW form, with two of them virilised as Prader 3 and the other two as Prader 4. Virilisation with clitoromegaly was also observed in one female, who presented premature adrenarche and carried the least severe p.Pro30Leu mutation.Conclusion: The frequency of the underlying mutations in our patients, with the classic form of CAH, varies but were quite similar to the ones reported in the Mediterranean region. Therefore, the identification of severe CYP21A2 defects in Cypriot patients and their comparison with the incidence and severity in different populations, will create a valuable diagnostic tool for genetic counseling in the classic form of CAH.

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Different Gene Defects in the Salt‐Wasting (SW), Simple Virilizing (SV), and Nonclassical (NC) Types of Congenital Adrenal Hyperplasia (CAH)

Cited by 8 publications

References 12 publications

Hla Associations in Patients With Polycystic Ovaries and in Patients With Congenital Adrenal Hyperplasia Caused by 21‐hydroxylase Deficiency

Hla Associations in Patients With Polycystic Ovaries and in Patients With Congenital Adrenal Hyperplasia Caused by 21‐hydroxylase Deficiency

Recent advances in diagnosis, treatment, and outcome of congenital adrenal hyperplasia due to 21-hydroxylase deficiency

Genotype Is Associated to the Degree of Virilization in Patients With Classic Congenital Adrenal Hyperplasia

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