scholarly journals ACQUISITION OF ALDOSTERONE BIOSYNTHETIC CAPACITY IN CONGENITAL ADRENAL HYPERPLASIA WITH HOMOZYGOUS DELETION OF THE GENE ENCODING P450/C21

1987 ◽  
Vol 21 (4) ◽  
pp. 254A-254A
Author(s):  
Phyllis W Speiser ◽  
Perrin C White ◽  
Maria I New
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Homozygous Deletion ◽  
Adrenal Hyperplasia ◽  
Gene Encoding

scholarly journals Premature Moustache As Presenting Symptom of Nonclassic Congenital Adrenal Hyperplasia due to 2 Uncommon Mutations of theCYP21A2Gene

2011 ◽  
Vol 2011 ◽  
pp. 1-3 ◽  
Author(s):  
Guy Massa ◽  
Philippe Gillis ◽  
Marianne Schwartz
Keyword(s):  
Genetic Analysis ◽  
Congenital Adrenal Hyperplasia ◽  
Adrenal Hyperplasia ◽  
Gene Encoding ◽  
Rare Mutations

A Turkish boy was referred at the age of 3 6/12 years for the evaluation of a premature moustache. No other signs of virilisation were present. The endocrine evaluation led to the diagnosis of nonclassic congenital adrenal hyperplasia. Genetic analysis revealed 2 rare mutations of theCYP21A2gene, the gene encoding for the 21-hydroxylase enzyme: a recently reported R132C mutation in exon 3 and a R339H mutation in exon 8, both reported in the nonclassic CAH. An early moustache, for which the term premature moustache can be coined, can be the presenting symptom of nonclassic CAH. In all children presenting with a sex or age inappropriate development of a moustache, an endocrine evaluation is indicated.

scholarly journals Prevalence of Nonclassic Congenital Adrenal Hyperplasia in Turkish Children Presenting with Premature Pubarche, Hirsutism, or Oligomenorrhoea

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Cigdem Binay ◽  
Enver Simsek ◽  
Oguz Cilingir ◽  
Zafer Yuksel ◽  
Ozden Kutlay ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Mutational Analysis ◽  
Autosomal Recessive Disorder ◽  
Adrenal Hyperplasia ◽  
Acth Stimulation ◽  
Gene Encoding ◽  
Turkish Children ◽  
17 Hydroxyprogesterone ◽  
Ovarian Syndrome ◽  
Premature Pubarche

Background. Nonclassic congenital adrenal hyperplasia (NCAH), caused by mutations in the gene encoding 21-hydroxylase, is a common autosomal recessive disorder. In the present work, our aim was to determine the prevalence of NCAH presenting as premature pubarche (PP), hirsutism, or polycystic ovarian syndrome (PCOS) and to evaluate the molecular spectrum ofCYP21A2mutations in NCAH patients.Methods. A total of 126 patients (122 females, 4 males) with PP, hirsutism, or PCOS were included in the present study. All patients underwent an ACTH stimulation test. NCAH was considered to be present when the stimulated 17-hydroxyprogesterone plasma level was >10 ng/mL.Results. Seventy-one of the 126 patients (56%) presented with PP, 29 (23%) with PCOS, and 26 (21%) with hirsutism. Six patients (4,7%) were diagnosed with NCAH based on mutational analysis. Four different mutations (Q318X, P30L, V281L, and P453S) were found in six NCAH patients. One patient with NCAH was a compound heterozygote for this mutation, and five were heterozygous.Conclusion. NCAH should be considered as a differential diagnosis in patients presenting with PP, hirsutism, and PCOS, especially in countries in which consanguineous marriages are prevalent.

scholarly journals Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency*

2000 ◽  
Vol 21 (3) ◽  
pp. 245-291 ◽  
Author(s):  
Perrin C. White ◽  
Phyllis W. Speiser
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
External Genitalia ◽  
Clinical Severity ◽  
Sodium Balance ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Gene Encoding ◽  
Salt Wasting ◽  
Direct Mutation ◽  
21 Hydroxylase Deficiency

Abstract More than 90% of cases of congenital adrenal hyperplasia (CAH, the inherited inability to synthesize cortisol) are caused by 21-hydroxylase deficiency. Females with severe, classic 21-hydroxylase deficiency are exposed to excess androgens prenatally and are born with virilized external genitalia. Most patients cannot synthesize sufficient aldosterone to maintain sodium balance and may develop potentially fatal “salt wasting” crises if not treated. The disease is caused by mutations in the CYP21 gene encoding the steroid 21-hydroxylase enzyme. More than 90% of these mutations result from intergenic recombinations between CYP21 and the closely linked CYP21P pseudogene. Approximately 20% are gene deletions due to unequal crossing over during meiosis, whereas the remainder are gene conversions—transfers to CYP21 of deleterious mutations normally present in CYP21P. The degree to which each mutation compromises enzymatic activity is strongly correlated with the clinical severity of the disease in patients carrying it. Prenatal diagnosis by direct mutation detection permits prenatal treatment of affected females to minimize genital virilization. Neonatal screening by hormonal methods identifies affected children before salt wasting crises develop, reducing mortality from this condition. Glucocorticoid and mineralocorticoid replacement are the mainstays of treatment, but more rational dosing and additional therapies are being developed.

scholarly journals Functional studies of novel CYP21A2 mutations detected in Norwegian patients with congenital adrenal hyperplasia

2014 ◽  
Vol 3 (2) ◽  
pp. 67-74 ◽  
Author(s):  
Ingeborg Brønstad ◽  
Lars Breivik ◽  
Paal Methlie ◽  
Anette S B Wolff ◽  
Eirik Bratland ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Congenital Adrenal Hyperplasia ◽  
Adrenal Hyperplasia ◽  
Gene Encoding ◽  
Salt Wasting ◽  
Functional Studies ◽  
Norwegian Population ◽  
Liquid Chromatography Tandem Mass ◽  
17 Hydroxyprogesterone

In about 95% of cases, congenital adrenal hyperplasia (CAH) is caused by mutations in CYP21A2 gene encoding steroid 21-hydroxylase (21OH). Recently, we have reported four novel CYP21A2 variants in the Norwegian population of patients with CAH, of which p.L388R and p.E140K were associated with salt wasting (SW), p.P45L with simple virilising (SV) and p.V211M+p.V281L with SV to non-classical (NC) phenotypes. We aimed to characterise the novel variants functionally utilising a newly designed in vitro assay of 21OH enzyme activity and structural simulations and compare the results with clinical phenotypes. CYP21A2 mutations and variants were expressed in vitro. Enzyme activity was assayed by assessing the conversion of 17-hydroxyprogesterone to 11-deoxycortisol by liquid chromatography tandem mass spectroscopy. PyMOL 1.3 was used for structural simulations, and PolyPhen2 and PROVEAN for predicting the severity of the mutants. The CYP21A2 mutants, p.L388R and p.E140K, exhibited 1.1 and 11.3% of wt 21OH enzyme activity, respectively, in vitro. We could not detect any functional deficiency of the p.P45L variant in vitro; although prediction tools suggest p.P45L to be pathogenic. p.V211M displayed enzyme activity equivalent to the wt in vitro, which was supported by in silico analyses. We found good correlations between phenotype and the in vitro enzyme activities of the SW mutants, but not for the SV p.P45L variant. p.V211M might have a synergistic effect together with p.V281L, explaining a phenotype between SV and NC CAH.

scholarly journals Mutations in CYP11B1 and Congenital Adrenal Hyperplasia in Moroccan Jews

2005 ◽  
Vol 90 (9) ◽  
pp. 5463-5465 ◽  
Author(s):  
Tamar Paperna ◽  
Ruth Gershoni-Baruch ◽  
Kader Badarneh ◽  
Leah Kasinetz ◽  
Ze’ev Hochberg
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Founder Mutation ◽  
Compound Heterozygote ◽  
Single Mutation ◽  
Carrier Rate ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Gene Encoding ◽  
High Incidence ◽  
Private Mutation

Abstract Context: In Jews of Moroccan descent (MJ), the prevalence of steroid 11β-hydroxylase deficiency (11-OHD) is relatively high, with a carrier rate estimated as approximately one in 40. A single mutation in the CYP11B1 gene (encoding 11β-hydroxylase), R448H, was suggested to account for the disease alleles in this population. Study Subjects: We screened 236 healthy MJ for R448H. Results: Only two of the subjects screened were found to be carriers, suggesting that the R448H allele frequency is lower than was assumed previously. An R448H/R448C compound heterozygote patient, diagnosed with 11-OHD, was identified. However, a subsequent screen of MJ subjects for R448C failed to detect any carriers, suggesting that this was a private mutation of this family. Conclusion: The high incidence of 11-OHD in MJ, therefore, is only partially explained by the presence of R448H as a founder mutation.

Alu Sx repeat-induced homozygous deletion of the StAR gene causes lipoid congenital adrenal hyperplasia

2012 ◽  
Vol 130 (1-2) ◽  
pp. 1-6 ◽  
Author(s):  
Antje Eiden-Plach ◽  
Huy-Hoang Nguyen ◽  
Ursula Schneider ◽  
Michaela F. Hartmann ◽  
Rita Bernhardt ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Homozygous Deletion ◽  
Adrenal Hyperplasia ◽  
Star Gene

scholarly journals A novel mutation in CYP17A1 gene leads to congenital adrenal hyperplasia: A case report

2019 ◽  
Author(s):  
Majid Nazari ◽  
Mohammad Yahya Vahidi Mehrjardi ◽  
Nosrat Neghab ◽  
Mahdi Aghabagheri ◽  
Nasrin Ghasemi
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Autosomal Recessive ◽  
Clinical Symptoms ◽  
Novel Mutation ◽  
Autosomal Recessive Disorder ◽  
Homozygous Deletion ◽  
Blood Levels ◽  
Primary Amenorrhea ◽  
Adrenal Hyperplasia ◽  
Lyase Deficiency

Background: Congenital adrenal hyperplasia is a rare autosomal recessive disorder where the mutation in P450 family 17 subfamily A member 1 gene (CYP17A1) is involved in its etiology. The disorder represents itself with low blood levels of estrogens, androgens, and cortisol that generally couples with hypertension, Hypokalemia, sexual primary amenorrhea, infantilism and in affected individuals. Case: In this study, the CYP17A1 gene in a 14-year-old female was examined. The karyotype of the patient was 46, XX, and the analysis of the CYP17A1 gene by Sanger sequencing revealed a novel homozygous deletion c.1052-1054CCT which led to isolated 17,20-lyase deficiency. Conclusion: In conclusion, this study report an in-frame deletion which results in isolated 17, 20-lyase deficiency, and the mutation might be used for diagnosis in other patients with distinctive clinical symptoms.

scholarly journals Clinical, genetic, and structural basis of congenital adrenal hyperplasia due to 11β-hydroxylase deficiency

2017 ◽  
Vol 114 (10) ◽  
pp. E1933-E1940 ◽  
Author(s):  
Ahmed Khattab ◽  
Shozeb Haider ◽  
Ameet Kumar ◽  
Samarth Dhawan ◽  
Dauood Alam ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Severe Disease ◽  
Gene Mutations ◽  
Structural Basis ◽  
Missense Mutations ◽  
Adrenal Hyperplasia ◽  
Clinical Genetic ◽  
Hydroxylase Deficiency ◽  
Gene Encoding ◽  
21 Hydroxylase Deficiency

Congenital adrenal hyperplasia (CAH), resulting from mutations inCYP11B1, a gene encoding 11β-hydroxylase, represents a rare autosomal recessive Mendelian disorder of aberrant sex steroid production. Unlike CAH caused by 21-hydroxylase deficiency, the disease is far more common in the Middle East and North Africa, where consanguinity is common often resulting in identical mutations. Clinically, affected female newborns are profoundly virilized (Prader score of 4/5), and both genders display significantly advanced bone ages and are oftentimes hypertensive. We find that 11-deoxycortisol, not frequently measured, is the most robust biochemical marker for diagnosing 11β-hydroxylase deficiency. Finally, computational modeling of 25 missense mutations ofCYP11B1revealed that specific modifications in the heme-binding (R374W and R448C) or substrate-binding (W116C) site of 11β-hydroxylase, or alterations in its stability (L299P and G267S), may predict severe disease. Thus, we report clinical, genetic, hormonal, and structural effects ofCYP11B1gene mutations in the largest international cohort of 108 patients with steroid 11β-hydroxylase deficiency CAH.

Sign in / Sign up

Export Citation Format

Share Document