scholarly journals Genetic analysis does not confirm non-classical congenital adrenal hyperplasia in more than a third of the women followed with this diagnosis

HORMONES ◽  
2014 ◽  
Author(s):  
Valeria Alcantara-Aragon ◽  
Silvia Martinez-Couselo ◽  
Diana Tundidor-Rengel ◽  
Susan Webb ◽  
Gemma Carreras ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Congenital Adrenal Hyperplasia ◽  
Adrenal Hyperplasia

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.

Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency: An Update on Genetic Analysis of CYP21A2 Gene

2020 ◽  
Author(s):  
Berta Carvalho ◽  
C.Joana Marques ◽  
Rita Santos-Silva ◽  
Manuel Fontoura ◽  
Davide Carvalho ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Congenital Adrenal Hyperplasia ◽  
Late Onset ◽  
Molecular Genetic Analysis ◽  
Clinical Severity ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Cyp21a2 Gene ◽  
Pathogenic Variants ◽  
21 Hydroxylase Deficiency

AbstractCongenital Adrenal Hyperplasia is a group of genetic autosomal recessive disorders that affects adrenal steroidogenesis in the adrenal cortex. One of the most common defects associated with Congenital Adrenal Hyperplasia is the deficiency of 21-hydroxylase enzyme, responsible for the conversion of 17-hydroxyprogesterone to 11-deoxycortisol and progesterone to deoxycorticosterone. The impairment of cortisol and aldosterone production is directly related to the clinical form of the disease that ranges from classic or severe to non-classic or mild late onset. The deficiency of 21-hydroxylase enzyme results from pathogenic variants on CYP21A2 gene that, in the majority of the cases, compromise enzymatic activity and are strongly correlated with the clinical severity of the disease. Due to the exceptionally high homology and proximity between the gene and the pseudogene, more than 90% of pathogenic variants result from intergenic recombination. Around 75% are deleterious variants transferred from the pseudogene by gene conversion, during mitosis. About 20% are due to unequal crossing over during meiosis and lead to duplications or deletions on CYP21A2 gene. Molecular genetic analysis of CYP21A2 variants is of major importance for confirmation of clinical diagnosis, predicting prognosis and for an appropriate genetic counselling. In this review we will present an update on the genetic analysis of CYP21A2 gene variants in CAH patients performed in our department.

scholarly journals Molecular genetic analysis of CYP21A2 gene in patients with congenital adrenal hyperplasia

2012 ◽  
Vol 16 (3) ◽  
pp. 384 ◽  
Author(s):  
AriacheryC Ammini ◽  
Arundhati Sharma ◽  
Rajesh Khadgawat ◽  
Eunice Marumudi ◽  
Bindu Kulshreshtha ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Congenital Adrenal Hyperplasia ◽  
Molecular Genetic ◽  
Molecular Genetic Analysis ◽  
Adrenal Hyperplasia ◽  
Cyp21a2 Gene

scholarly journals The classical form of congenital adrenal hyperplasia-clinical characteristics and genetic analysis

2016 ◽  
Author(s):  
Elwira Przybylik-Mazurek ◽  
Anna Kurzynska ◽  
Anna Skalniak ◽  
Jakub Piatkowski ◽  
Alicja Hubalewska-Dydejczyk
Keyword(s):  
Genetic Analysis ◽  
Congenital Adrenal Hyperplasia ◽  
Clinical Characteristics ◽  
Adrenal Hyperplasia ◽  
Classical Form

scholarly journals Variations in the Initial Presentation of a Rare Congenital Adrenal Hyperplasia: Steroidogenic Acute Regulatory Deficiency

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A164-A164
Author(s):  
Priyanka Saha ◽  
Juanita Hodax ◽  
Sara A DiVall ◽  
Grace Kim ◽  
Alyssa Huang
Keyword(s):  
Genetic Analysis ◽  
Congenital Adrenal Hyperplasia ◽  
Sex Reversal ◽  
Full Term ◽  
Adrenal Crisis ◽  
Acth Level ◽  
Adrenal Hyperplasia ◽  
Pelvic Mri ◽  
Steroidogenic Acute Regulatory ◽  
Star Gene

Abstract Background: Steroidogenic Acute Regulatory (StAR) deficiency is a rare form of congenital adrenal hyperplasia characterized by dysregulated cholesterol transport mediated by StAR enzyme across mitochondrial membranes. Adrenal dysfunction is due to the two-hit hypothesis: 1) defective StAR protein and 2) cholesterol accumulation in the adrenals and gonads. With variable cellular damage, adrenal crisis can occur early or late. Clinical cases: We present two cases of StAR deficiency with contrasting presentations. Case 1: A 9-day old ex full term female from a nonconsanguineous union presented to a rural hospital with hypothermia, lethargy, and poor feeding. She had hypoglycemia 41 mg/dL (60–105), hyponatremia 120 mEq/L (135–145), hyperkalemia 7.7 mEq/L (3.5–5.5) and cortisol < 0.4 ug/dL (4.5–23). Baby was started on hydrocortisone (HCT) 100 mg/m2 and one-time fludrocortisone (FCT). She decompensated requiring chest compressions, intubation and pressors. She was transferred to our institution. Newborn screen was normal; she had typical female external genitalia. US demonstrated a uterus; ovaries and adrenals were not identified. Upon extubation and clinical improvement, her HCT was weaned to physiologic doses. She became hyponatremic requiring FCT and salt supplements. Post-HCT wean, ACTH level was 304 pg/mL (7–63) with aldosterone < 4.0 ng/dL (6.5–86). Karyotype was 46,XX. Genetic analysis revealed a novel heterozygous likely pathogenic variant in the STAR gene, (STAR c.65-12_68del variant) without defect in the other STAR gene. Case 2: A 9-month-old ex full-term female of Iraqi descent from a nonconsanguineous union presented with fatigue, poor oral intake and weight loss from 50%-ile to 3%-ile. She had hyponatremia 122 mEq/L, hyperkalemia 8.0 mEq/L, but was normoglycemic. She was normotensive; EKG was normal. Parents noted progressive hyperpigmentation including her gums, palmar and plantar creases. She had typical external female genitalia with a hypoplastic clitoris (2 mm x 2 mm). ACTH stimulation test showed low cortisol (0.5 ug/dL) at 60 minutes. She was treated with HCT 100 mg/m2 for 5 days, then tapered to maintenance dosing, with FCT and salt supplements. Her ACTH level returned > 5000 pg/ml. Aldosterone, 17-OH-Progesterone, 17-OH-Pregnenolone, 11-Deoxycortisol and androstenedione were undetectable. Pelvic US did not identify uterus or ovaries. Pelvic MRI identified bilateral inguinal testes with enlarged adrenal glands. Karyotype was 46, XY. We suspected StAR deficiency with sex-reversal. Genetic analysis revealed a known homozygous mutation in STAR (c.545G>A). Conclusion: StAR deficiency is clinically indistinguishable from P450scc deficiency and genetic testing is needed. Both entities can present with early or delayed adrenal crisis. While classic for StAR deficiency, adrenal enlargement is inconsistent. Karyotype is vital to identify sex reversal.

scholarly journals Comprehensive Genetic Analysis of 182 Unrelated Families with Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency

2011 ◽  
Vol 96 (1) ◽  
pp. E161-E172 ◽  
Author(s):  
Gabriela P. Finkielstain ◽  
Wuyan Chen ◽  
Sneha P. Mehta ◽  
Frank K. Fujimura ◽  
Reem M. Hanna ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Congenital Adrenal Hyperplasia ◽  
Mutation Analysis ◽  
De Novo ◽  
Uniparental Disomy ◽  
Compound Heterozygous ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Study Objective ◽  
21 Hydroxylase Deficiency

Background: Genetic analysis is commonly performed in patients with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. Study Objective: The objective of the study was to describe comprehensive CYP21A2 mutation analysis in a large cohort of CAH patients. Methods: Targeted CYP21A2 mutation analysis was performed in 213 patients and 232 parents from 182 unrelated families. Complete exons of CYP21A2 were sequenced in patients in whom positive mutations were not identified by targeted mutation analysis. Copy number variation and deletions were determined using Southern blot analysis and PCR methods. Genotype was correlated with phenotype. Results: In our heterogeneous U.S. cohort, targeted CYP21A2 mutation analysis did not identify mutations on one allele in 19 probands (10.4%). Sequencing identified six novel mutations (p.Gln262fs, IVS8+1G>A, IVS9-1G>A, p.R408H, p.Gly424fs, p.R426P) and nine previously reported rare mutations. The majority of patients (79%) were compound heterozygotes and 69% of nonclassic (NC) patients were compound heterozygous for a classic and a NC mutation. Duplicated CYP21A2 haplotypes, de novo mutations and uniparental disomy were present in 2.7% of probands and 1.9 and 0.9% of patients from informative families, respectively. Genotype accurately predicted phenotype in 90.5, 85.1, and 97.8% of patients with salt-wasting, simple virilizing, and NC mutations, respectively. Conclusions: Extensive genetic analysis beyond targeted CYP21A2 mutational detection is often required to accurately determine genotype in patients with CAH due to the high frequency of complex genetic variation.

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