Publications by authors named "Veronique Tardy"

23 Publications

  • Page 1 of 1

Prenatal diagnosis of steroid 21-hydroxylase-deficient congenital adrenal hyperplasia: Experience from a tertiary care centre in India.

Indian J Med Res 2017 Feb;145(2):194-202

Department of Pediatrics, Division of Genetics, All India Institute of Medical Sciences, New Delhi, India.

Background & Objectives: Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder with a wide range of clinical manifestations. The disease is attributed to mutations in CYP21A2 gene encoding 21-hydroxylase enzyme. In view of severe phenotype in salt-losing cases, issues related to genital ambiguity in girls and precocity in boys, most families opt for prenatal testing and termination of affected foetus. CAH can be diagnosed in utero through direct molecular analysis of CYP21A2 gene, using DNA extracted from foetal tissues or cells obtained from chorionic villus sampling or amniocentesis. The objective of this study was to evaluate the feasibility and accuracy of prenatal diagnosis (PND) using sequencing and multiplex ligation probe amplification (MLPA) methods in families at risk for CAH.

Methods: Fifteen pregnant women at risk of having an affected offspring with CAH were included in this study. Ten families had previous affected children with salt-wasting/simple virilising form of CAH and five families did not have live children but had a high index of suspicion for CAH in previous children based on history or records. Mutation analysis was carried out by Sanger sequencing and MLPA method.

Results: Seven different mutations were identified in 15 families. Deletions and I2g mutation were the most common. Of the 15 foetuses analyzed, nine were unaffected while six were affected. Unaffected foetuses were delivered, they were clinically normal and their genotype was found to be concordant to the prenatal report. All except two families reported in the second trimester. None of the couples opted for prenatal treatment.

Interpretation & Conclusions: Our preliminary findings show that PND by direct mutation analysis along with MLPA is a feasible strategy that can be offered to families at risk.
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http://dx.doi.org/10.4103/ijmr.IJMR_329_16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5501051PMC
February 2017

Growth curves for congenital adrenal hyperplasia from a national retrospective cohort.

J Pediatr Endocrinol Metab 2016 Dec;29(12):1379-1388

Background: In congenital adrenal hyperplasia (CAH), adjusting hydrocortisone dose during childhood avoids reduced adult height. However, there are currently no CAH-specific charts to monitor growth during treatment. Our objective was to elaborate growth reference charts and bone maturation data for CAH patients.

Methods: We conducted a retrospective observational cohort study, in 34 French CAH centers. Patients were 496 children born 1970-1991 with genetically proven 21-hydroxylase deficiency. Their growth and bone maturation data were collected until age 18 together with adult height, puberty onset, parental height, and treatment. The mean (SD) heights were modeled from birth to adulthood. The median±1 SD and ±2 SDs model-generated curves were compared with the French references. A linear model for bone maturation and a logistic regression model for the probability of short adult height were built.

Results: Growth charts were built by sex for salt wasting (SW) and simple virilizing (SV) children treated before 1 year of age. In girls and boys, growth was close to that of the general French population up to puberty onset. There was almost no pubertal spurt and the mean adult height was shorter than that of the general population in girls (-1.2 SD, 156.7 cm) and boys (-1.0 SD, 168.8 cm). Advanced bone age at 8 years had a strong impact on the risk of short adult height (OR: 4.5 per year advance).

Conclusions: The 8-year bone age is a strong predictor of adult height. It will help monitoring the growth of CAH-affected children.
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http://dx.doi.org/10.1515/jpem-2016-0156DOI Listing
December 2016

Evolution of steroids during pregnancy: Maternal, placental and fetal synthesis.

Ann Endocrinol (Paris) 2016 Jun 4;77(2):82-9. Epub 2016 May 4.

Service d'hormonologie, endocrinologie moléculaire et maladies rares, CPBE, groupement hospitalier Lyon-Est, 69677 Lyon-Bron, France.

Progesterone, estrogens, androgens and glucocorticoids are involved in pregnancy from implantation to parturition. Their biosynthesis and their metabolism result from complex pathways involving the fetus, the placenta and the mother. The absence of expression of some steroïdogenic enzymes as CYP17 in placenta and in adrenal fetal zone and the better determination of the onset and variation of others especially HSD3B2 during the pregnancy explain the production of the steroid hormones. Moreover the consequences of some disorders of steroidogenesis (especially aromatase, POR, CYP11A1 and 21-hydroxylase deficiencies) in fetus and mother during the pregnancy have permit to elucidate these complex pathways. This better knowledge of steroid hormones production associated with their dosages in maternal plasma/urine or amniotic fluid using new specific assays as LC-MS MS could facilitate the follow-up of normal and pathological pregnancies. Moreover, these advances should be a basis to evaluate the impact of multiple pathologies of the pregnancy and pharmacologic and xenobiotic consequences on their metabolism.
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http://dx.doi.org/10.1016/j.ando.2016.04.023DOI Listing
June 2016

Laparoscopic-assisted vaginal pull-through: A new approach for congenital adrenal hyperplasia patients with high urogenital sinus.

Afr J Paediatr Surg 2015 Jul-Sep;12(3):177-80

Department of Paediatric Surgery, University Claude Bernard Lyon 1, Hôpital Femme Mère Enfant, 69677 Bron Cedex, France.

Background: To open vaginal cavity to the pelvic floor is part of surgical treatment for urogenital sinus (UGS) in girls with congenital adrenal hyperplasia (CAH). For high UGS, this operative procedure can be challenging and may jeopardise urinary continence. Combined perineal and laparoscopic approaches could be useful to minimise perineal dissection and to facilitate the vaginal lowering.

Patients And Methods: We report the procedure of a laparoscopic-assisted vaginal pull-through for supra-sphincteric UGS in a 5-year-old girl with CAH. Laparoscopic dissection of the vagina from the posterior wall of the bladder and urethra, division of the confluence and vaginal pull-through to the perineum are described.

Discussion: The technique is derived from laparoscopic-assisted treatment for high ano-rectal malformations. Compared with current procedures for treatment for high UGS, laparoscopic-assisted approach allows mobilising vagina with minimal dissection of perineum and complete preservation of urethra. Another major advantage is to provide a direct vision for dissection of the space between rectum and urethra prior to vaginal pull-through.

Conclusion: Laparoscopic-assisted vaginal pull-through appears to be an interesting approach for high UGS in CAH patients, reducing dissection and risk of urinary incontinence. This new approach needs to be strengthened by other cases.
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http://dx.doi.org/10.4103/0189-6725.170191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4955429PMC
December 2016

Secondary amenorrhoea associated with high serum 17-hydroxyprogesterone levels revealing a heterozygous CYP21A2 mutation in a woman with Addison disease.

Clin Endocrinol (Oxf) 2015 Apr 11;82(4):620-2. Epub 2014 Dec 11.

Service d' Endocrinologie, Hôpital Erasme, Université Libre de Bruxelles, Bruxelles, Belgique; Assistance Publique Hôpitaux de Paris, Service d'Endocrinologie et des Maladies de la Reproduction, Hôpital de Bicêtre, Université Paris Sud, Le Kremlin Bicêtre, France.

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http://dx.doi.org/10.1111/cen.12646DOI Listing
April 2015

Adrenal rest tissue in gonads of patients with classical congenital adrenal hyperplasia: multicenter study of 45 French male patients.

Ann Endocrinol (Paris) 2012 Dec 3;73(6):515-22. Epub 2012 Nov 3.

Adult Endocrinology Unit, University Hospital of Tours, 2, boulevard Tonnelé, 37044 Tours cedex 9, France.

Objectives: Several cases of testicular adrenal rest tumours have been reported in men with congenital adrenal hyperplasia (CAH) due to the classical form of 21-hydroxylase deficiency but the prevalence has not been established. The aims of this report were to evaluate the frequency of testicular adrenal rest tissue in this population in a retrospective multicentre study involving eight endocrinology centres, and to determine whether treatment or genetic background had an impact on the occurrence of adrenal rest tissue.

Material And Methods: Testicular adrenal rest tissue (TART) was sought clinically and with ultrasound examination in forty-five males with CAH due to the classical form of 21-hydroxylase deficiency. When the diagnosis of testicular adrenal rest tumours was sought, good observance of treatment was judged on biological concentrations of 17-hydroxyprogesterone (17OHP), delta4-androstenedione, active renin and testosterone. The results of affected and non-affected subjects were compared.

Results: TART was detected in none of the 18 subjects aged 1 to 15years but was detected in 14 of the 27 subjects aged more than 15years. Five patients with an abnormal echography result had no clinical signs. Therapeutic control evaluated at diagnosis of TART seemed less effective when diagnosis was made in patients with adrenal rest tissue compared to TART-free subjects. Various genotypes were observed in patients with or without TART.

Conclusion: Due to the high prevalence of TART in classical CAH and the delayed clinical diagnosis, testicular ultrasonography must be performed before puberty and thereafter regularly during adulthood even if the clinical examination is normal.
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http://dx.doi.org/10.1016/j.ando.2012.09.005DOI Listing
December 2012

Efficiency of neonatal screening for congenital adrenal hyperplasia due to 21-hydroxylase deficiency in children born in mainland France between 1996 and 2003.

Arch Pediatr Adolesc Med 2012 Feb;166(2):113-20

Department of Biostatistics, Groupe hospitalier Cochin-Saint Vincent de Paul and University Paris Descartes, France.

Objective: To assess the efficiency of the French national screening program for 21-hydroxylase deficiency (21-OHD). Neonatal screening for congenital adrenal hyperplasia due to 21-OHD is mainly intended to prevent death due to salt wasting but remains controversial because of the number of false-positive results and the ease with which most female cases can be identified by virilized genitalia at birth.

Design: Population-based study.

Setting: National neonatal screening program, pediatric endocrinologists nationwide, and reference center for genotyping.

Participants: All neonates screened for 21-OHD in mainland France between January 1, 1996, and December 31, 2003.

Outcome Measures: Screening efficiency indicators, disease severity, contribution of screening to early diagnosis, and disease-specific mortality before and during the study period.

Results: A total of 6,012,798 neonates were screened; results in 15,407 were considered positive for 21-OHD. Three hundred eighty-three cases were identified, giving a prevalence of 1 for every 15,699 births. The positive predictive value of screening was 2.3% (95% CI, 2.1%-2.6%), with a sensitivity of 93.5% (90.9%-95.9%) and a specificity of 99.7% (99.7%-99.7%). The false-positive rate was particularly high in preterm infants, for which the positive predictive value was 0.4% (95% CI, 0.2%-0.5%). Screening allowed clinical diagnosis in 162 of 383 cases (42.3%), with the others being detected clinically or through family history. There was a trend toward declining neonatal mortality due to 21-OHD.

Conclusions: In this large population-based study, the efficiency of routine 21-OHD screening was moderate in neonates born at term and very low in preterm neonates. We recommend the discontinuation of screening, as currently performed in France, in preterm neonates.
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http://dx.doi.org/10.1001/archpediatrics.2011.774DOI Listing
February 2012

Molecular defects of the CYP21A2 gene in Greek-Cypriot patients with congenital adrenal hyperplasia.

Horm Res Paediatr 2011 14;75(3):180-6. Epub 2010 Sep 14.

Paediatric Endocrine Unit, Department of Paediatrics, Makarios Hospital, Nicosia, Cyprus.

Background/aim: To determine the mutations in the CYP21A2 gene in Greek-Cypriots with congenital adrenal hyperplasia (CAH) and attempt a genotype-phenotype correlation.

Subjects And Methods: Molecular analysis was performed by multiplex ligation-dependent probe amplification and direct sequencing of PCR products of the CYP21A2 gene in 32 CAH patients.

Results: The most frequent genetic defect in the classic salt-wasting and simple virilizing forms was the IVS2-13A/C>G (55%) mutation, followed by Large lesion (20%) and in the non-classical form, the p.V281L (79.5%). Genotypes were categorized in 4 mutation groups (null, A, B and C). All 3 patients in the null group manifested the salt-wasting form and all 6 patients in mutation group A presented with the classical form. One patient in group B had the simple virilizing form and 22 patients in group C exhibited the non-classical form.

Conclusion: The spectrum of mutations of the CYP21A2 gene in our population is comparable to the most common reported in similar ethnic groups. The knowledge of the ethnic specificity of the CYP21A2 mutations represents a valuable diagnostic tool for all forms of CAH.
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http://dx.doi.org/10.1159/000320040DOI Listing
July 2011

Fertility in women with nonclassical congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

J Clin Endocrinol Metab 2010 Mar 15;95(3):1182-90. Epub 2010 Jan 15.

Department of Reproductive Endocrinology, Hôpital Pitié-Salpêtrière, 47 Boulevard de l'Hôpital, 75013 Paris, France.

Objective: In contrast to subfertility often reported in women suffering from the classical form of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, fertility in nonclassical CAH (NC-CAH) has been rarely studied. Our objective was to evaluate fertility in NC-CAH women.

Material And Methods: We studied 190 NC-CAH women (161 probands + 29 first degree relatives). Only 20 probands had consulted for infertility (12%), either alone or associated with hirsutism or menstrual cycle disorders. The diagnosis was established on post-ACTH 17-hydroxyprogesterone 10 ng/ml or greater and further characterized by CYP21A2 gene analysis.

Results: Ninety-five of the 190 women wanted pregnancy (aged 26.7 +/- 8.9 yr); 187 pregnancies occurred in 85 women, which resulted in 141 births in 82 of them. Ninety-nine pregnancies (52.9%) occurred before the diagnosis of NC-CAH (96 spontaneously and three with ovulation inducers) whereas 98 occurred after diagnosis (11 spontaneously and 77 with hydrocortisone treatment); 83% of pregnancies were obtained within 1 yr. The rate of miscarriages was 6.5% for pregnancies obtained with glucocorticoid treatment vs. 26.3% without. Two of the 141 infants (1.5%) were born with classical CAH.

Conclusion: Subfertility is mild in NC-CAH. However, the rate of miscarriages is lower in pregnancies occurring with glucocorticoid treatment and argues for treating NC-CAH women wanting pregnancy. In addition, considering the high rate of heterozygotes for CYP21A2 mutations in the general population, it is essential to genotype the partner of patients with a severe mutation to predict the risk of classical CAH and offer genetic counseling.
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http://dx.doi.org/10.1210/jc.2009-1383DOI Listing
March 2010

Premature pubarche in Mediterranean girls: high prevalence of heterozygous CYP21 mutation carriers.

Gynecol Endocrinol 2010 May;26(5):319-24

Unité d'Endocrinologie Pédiatrique, Hôpital Arnaud de Villeneuve, CHU-Montpellier et UM1, Montpellier, France.

Aim: This study investigated the prevalence and consequences of heterozygous CYP21A2 mutations in premature pubarche (PP) girls.

Main Finding: We investigated 36 French Mediterranean girls with isolated PP. We performed synacthen testing with 17OHP and 21-deoxycortisol evaluation, along with molecular analysis of the CYP21A2 gene in girls with abnormal elevation of one of these two adrenal steroids. Three girls (8.3%) had nonclassical adrenal hyperplasia, secondary to compound heterozygosity that associated at least one severe mutation for the three girls. A heterozygous mutation of the CYP21A2 gene was confirmed by molecular biology in eight girls (22%); a deletion of the CYP21A2 gene was found in one of them. Biological hyperandrogenism was found in the prepubertal CYP21A2 mutation carriers, whereas the four heterozygous girls who were followed long enough to have reached pubertal age presented biological and clinical hyperandrogenism.

Conclusions: We underline the high prevalence of heterozygous CYP21A2 mutations in girls with PP and demonstrate the usefulness of systematic screening by synacthen testing, both to improve their future clinical management and to prevent the transmission of classical adrenal hyperplasia to future offspring. Because of the severe metabolic and cardiovascular consequences of hyperandrogenism, long-term follow-up of these heterozygous patients is mandatory.
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http://dx.doi.org/10.3109/09513590903511505DOI Listing
May 2010

Precocious pubarche: distinguishing late-onset congenital adrenal hyperplasia from premature adrenarche.

J Clin Endocrinol Metab 2009 Aug 19;94(8):2835-40. Epub 2009 May 19.

Université Paris Descartes, Paris, France.

Context: Because precocious pubarche (PP) reveals late-onset congenital adrenal hyperplasia (LO-CAH) in 5 to 20% of cases, an adrenal stimulation test is recommended in all patients presenting with it. This test is stressful and expensive, and results are normal in more than 80% of cases.

Objective: Our objective was to identify clinical and plasma predictors of LO-CAH among patients presenting with PP.

Design, Setting, And Patients: We conducted a retrospective cohort study that included all patients seen for PP at our hospital between 1999 and 2006 (n = 238). All had undergone an ACTH test.

Main Outcome Measure: LO-CAH was defined by a post-ACTH 17-hydroxyprogesterone (17-OHP) plasma level greater than 10 ng/ml and confirmed by mutational analysis of the CYP21 gene. The association of standard clinical and laboratory indicators with LO-CAH was assessed.

Results: Ten (4%) of 238 patients had LO-CAH. Basal 17-OHP, Delta4-androstenedione, and testosterone plasma levels were significantly higher in these patients. A 2-ng/ml threshold for basal 17-OHP plasma levels offered 100% (95% CI, 69-100) sensitivity for the diagnosis of LO-CAH and 99% (95% CI, 96-100) specificity.

Conclusion: We identified three plasma predictors of LO-CAH in patients presenting with PP. A selective strategy based on a 2-ng/ml basal 17-OHP plasma level threshold would have safely avoided 99% of the unnecessary ACTH tests among our patients.
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http://dx.doi.org/10.1210/jc.2009-0314DOI Listing
August 2009

Transient hyper-17-hydroxyprogesteronemia: a clinical subgroup of patients diagnosed at neonatal screening for congenital adrenal hyperplasia.

Eur J Endocrinol 2009 Aug 18;161(2):285-92. Epub 2009 May 18.

Pediatric Endocrinology Unit, INSERM U845, Hôpital Necker-Enfants Malades, Paris Descartes University, 75748 Paris, France.

Objective: Neonatal screening for congenital adrenal hyperplasia (CAH) is characterized by a high false-positive rate, mainly among preterm and low birth weight infants. The aims of this study were to describe a subgroup of infants with transient serum hyper-17-hydroxyprogesteronemia (hyper-17-OHPemia) and to compare them with false positive and affected by 21-hydroxylase deficiency newborns.

Methods: We retrospectively analyzed the clinical data of all newborns positive at CAH neonatal screening, who were referred to our hospital to confirm the diagnosis from 2002 to 2006. They were submitted to clinical investigations and blood tests to evaluate 17-hydroxyprogesterone (17-OHP), renin, and electrolyte levels. CAH-unaffected newborns with increased serum 17-OHP were submitted to strict follow-up monitoring, which included an ACTH-stimulating test and genetic analysis of the 21-hydroxylase gene, until serum 17-OHP decreased.

Results: Thirty-seven newborns with gestational ages ranging from 33 to 40 weeks were studied. Eight infants (three male and five female) were affected by CAH (serum 17-OHP: 277.5 (210-921) nmol/l), 14 (ten male and four female) were false positives (17-OHP: 3.75 (0.3-8.4) nmol/l), and 15 (ten male and five female) showed a serum hyper-17-OHPemia (17-OHP: 15.9 (9.9-33) nmol/l). No mutations of the 21-hydroxylase gene were found in infants with hyper-17-OHPemia and their serum 17-OHP levels were normalized by the third month of life.

Conclusion: We identified a population of infants with transient serum hyper-17-OHPemia, and no clinical signs of disease or 21-hydroxylase gene mutations. No further investigations are necessary after birth in these newborns if 17-OHP levels decrease, other confirmatory tests such as ACTH-stimulation test or genotyping analysis are necessary only if symptoms appear.
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http://dx.doi.org/10.1530/EJE-09-0145DOI Listing
August 2009

Clinical and molecular characterization of a cohort of 161 unrelated women with nonclassical congenital adrenal hyperplasia due to 21-hydroxylase deficiency and 330 family members.

J Clin Endocrinol Metab 2009 May 10;94(5):1570-8. Epub 2009 Feb 10.

Department of Reproductive Endocrinology, Centre de References des Maladies Endocriniennes Rares de la Croissance, Assistance Publique-Hôpitaux de Paris Pitié-Salpêtrière, 75013 Paris, France.

Context: Nonclassical congenital adrenal hyperplasia (NC-CAH) due to partial 21-hydroxylase deficiency is one of the most frequent autosomal recessive diseases.

Objective: The aim of this study was to determine the genotype/phenotype relationship in probands and family members.

Patients And Methods: A total of 161 NC-CAH unrelated women diagnosed on late-onset symptoms, mainly hirsutism, and post-ACTH 17-hydroxyprogesterone more than 10 ng/ml, and 330 of their relatives was explored. CYP21A2 was genotyped in 124 probands.

Results: The most frequent mutation was V281L. One severe mutation was found in 63.7% of probands, and surprisingly two severe mutations in four probands. Contrasting with the absence of clinical differences, basal testosterone, and androstenedione, basal and post-ACTH 17-hydroxyprogesterone were significantly higher in probands carrying at least one severe mutation than in those with two mild mutations (P < 0.01). Among the 330 family members, 51 were homozygotes or compound heterozygotes, and 42 were clinically asymptomatic; 242 were heterozygotes and 37 unaffected. Post-ACTH 21-deoxycortisol (21dF) was significantly higher in heterozygotes than in unaffected, however, an overlap existed. In 12 heterozygotes, post-ACTH 21dF was below 0.55 ng/ml, the cutoff value usually accepted for suggesting heterozygosity.

Conclusions: The study of family members underlines the variable expression of NC-CAH even within a family, suggesting that modifier factors may modulate phenotype expression. Post-ACTH 21dF cannot reliably detect heterozygous subjects. Considering the high frequency of heterozygotes in the general population, it is essential to genotype the partner(s) of the patients with one severe mutation to offer genetic counseling.
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http://dx.doi.org/10.1210/jc.2008-1582DOI Listing
May 2009

CYP21A2 gene mutation analysis in Moroccan patients with classic form of 21-hydroxylase deficiency: high regional prevalence of p.Q318X mutation and identification of a novel p.L353R mutation.

Clin Chem Lab Med 2008 ;46(12):1707-13

Laboratoire de Biochimie, Centre d'Etude des Maladies Héréditaires du Métabolisme, Hôpital d'Enfants de Rabat, Rabat, Morocco.

Background: Congenital adrenal hyperplasia (CAH) is an autosomal recessive disease most often due to steroid 21-hydroxylase deficiency (21OHD). The incidence of the CYP21A2 gene mutations in 21OHD has been extensively studied in recent years. The p.Q318X mutation presents an ethnic-specific distribution with a higher prevalence (40%) in Tunisia.

Methods: A total of 20 Moroccan patients were studied, using PCR amplification and sequencing, to determine the mutation spectrum and to evaluate whether the incidence of the p.Q318X mutation is similar in Morocco and in Tunisia.

Results: Results revealed that 15 patients were with the salt wasting (SW) form and five with the simple virilizing (SV) form of the disease. All patients were homozygous or compound heterozygous for severe mutations of the CYP21A2 gene. The IVS2-13A/C>G was the most common mutation (47% of chromosomes) and the p.I172N (11%) was associated with the SV form. The p.Q318X was the second most frequent mutation (19.4%) with a regional distribution: the mutation was especially detected (75%) in patients from the midland of Morocco (Fez). We found a novel p.L353R mutation associated with the p.V281L mutation on the same chromosome in one patient at homozygous state.

Conclusions: Genotyping for the four common mutations (IVS2-13A/C>G, p.Q318X, large lesions of the CYP21A2 gene and p.I172N) should allow identifying the diseased alleles and providing genetic counseling in 94% of CAH Moroccan cases. The regional distribution of mutations should help in screening studies.
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http://dx.doi.org/10.1515/CCLM.2008.339DOI Listing
March 2009

Gene symbol: CYP21A2.

Hum Genet 2007 Apr;121(2):294

Hôpital Debrousse, Laboratoire de Biologie Moléculaire, 29 rue Soeur Bouvier, Lyon Cedex, France.

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April 2007

Gene symbol: CYP21A2.

Hum Genet 2007 Apr;121(2):293-4

Hôpital Debrousse, Laboratoire de Biologie Moléculaire, 29 rue Soeur Bouvier, Lyon Cedex, France.

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April 2007

Gene symbol: CYP21A2.

Hum Genet 2007 Apr;121(2):293

Laboratoire de Biologie Moléculaire, Hôpital Debrousse, 29 rue Soeur Bouvier, Lyon Cedex, France.

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April 2007

Gene symbol: CYP21A2.

Hum Genet 2007 Apr;121(2):292-3

Laboratoire de Biologie Moléculaire, Hôpital Debrousse, 29 rue Soeur Bouvier, Lyon Cedex, France.

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April 2007

Gene symbol: CYP21A2.

Hum Genet 2007 Apr;121(2):292

Laboratoire de Biologie Moléculaire, Hôpital Debrousse, 29 rue Soeur Bouvier, Lyon Cedex, France.

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April 2007

Gene symbol: CYP21A2.

Hum Genet 2007 Apr;121(2):293

Laboratoire de Biologie Moléculaire, Hôpital Debrousse, 29 rue Soeur Bouvier, Lyon Cedex, France.

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April 2007

Gene symbol: CYP21A2. Disease: steroid 21-hydroxylase deficiency.

Authors:
Veronique Tardy

Hum Genet 2006 Apr;119(3):363

Laboratoire de Biologie Moléculaire, Hôpital Debrousse, Lyon, France.

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April 2006

A novel 13-bp deletion in exon 1 of CYP21 gene causing severe congenital adrenal hyperplasia.

Diagn Mol Pathol 2005 Dec;14(4):250-2

Laboratoire de Génétique Humaine, Faculté de Médecine de Tunis, Tunisia.

Congenital adrenal hyperplasia (CAH) is a common autosomal recessive disorder mainly caused by defects in the steroid 21-hydroxylase gene (CYP21). In most cases, this defect is the result of gene conversion events between the functional CYP21 gene and the adjacent inactive pseudogene (CYP21P). Previous screening for mutations of 21-hydroxylase gene in 51 unrelated Tunisian CAH patients revealed 4 novel mutations that have not been reported to occur in the CYP21P pseudogene. The present paper describes the fifth new small 13-bp deletion in exon 1 found after sequencing the CYP21 gene of a Tunisian patient suffering from the salt-wasting form of CAH. The patient is a girl born to consanguineous parents; she is homozygous for a novel deletion. The 13-bp deletion causes a stop codon at amino acid 47, which is likely to result in an enzyme with no activity. Both parents are heterozygous for the small deletion as confirmed by nested PCR method. This novel mutation has not been reported to occur in the CYP21P pseudogene, indicating a casual mutagenic event rather than a conversion one.
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http://dx.doi.org/10.1097/01.pas.0000177797.81206.ebDOI Listing
December 2005

Molecular genetic analysis of Tunisian patients with a classic form of 21-hydroxylase deficiency: identification of four novel mutations and high prevalence of Q318X mutation.

J Clin Endocrinol Metab 2004 Jan;89(1):368-74

Laboratoire de Génétique Humaine, Faculté de Médecine de Tunis, 1006, Tunisie.

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders mainly due to defects in the steroid 21-hydroxylase (CYP21) gene. To determine the mutational spectrum in the Tunisian CAH population, the CYP21 active gene was analyzed in 51 unrelated patients using our cascade strategy (digestion by restriction enzyme, sequencing). All patients had a classical form of 21-hydroxylase deficiency. Mutations were detected in over 94% of the chromosomes examined. The most frequent mutation in the Tunisian CAH population was found to be Q318X, with large prevalence (35.3%), in contrast to 0.5-13.8% described in other series. Incidence of other mutations does not differ, as previously described: large deletions (19.6%), mutation in intron 2 (17.6%), and I172N (10.8%). Four novel mutations were found in four patients with the salt-wasting form. These four novel mutations include three point mutations that have not been reported to occur in the CYP21P pseudogene: R483W, W19X, 2669insC, and one small conversion of DNA sequence from exon 5 to exon 8. Our results have shown a good genotype/phenotype correlation in the case of most mutations. This is the first report of screening for mutations of 21-hydroxylase gene in the Tunisian population and even in the Arab population.
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http://dx.doi.org/10.1210/jc.2003-031056DOI Listing
January 2004