Ethnic disparity in 21-hydroxylase gene mutations identified in Pakistani congenital adrenal hyperplasia patients

Khan, Aysha Habib; Aban, Muniba; Raza, Jamal; Haq, Naeem Ul; Jabbar, Abdul; Moatter, Tariq

doi:10.1186/1472-6823-11-5

Cited by 21 publications

(13 citation statements)

References 13 publications

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“…Similar genetic homogeneity was detected in the Yupik Eskimos from Western Alaska where high incidence of SWCAH and only homozygosity for the In2G mutation was found 1 . Khan et al found a high variety of mutations in patients with CAH in different Indian ethnicities, except in the Urdu ethnicity, where 8 out of 10 carried In2G mutation of which 5 were homozygous 36,37 . However, connection between the Roma and the Urdu populations remains to be explored.…”

Section: Discussionmentioning

confidence: 61%

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First insights into the genetics of 21‐hydroxylase deficiency in the Roma population

Kočova

Anastasovska

Petlichkovski

et al. 2021

Clinical Endocrinology

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Background 21‐hydroxylase deficiency (21OHD) is an autosomal recessive disorder with an incidence of 1:10,000‐1:20,000 and is the result of various mutations in the CYP21A2 gene. 21OHD has been described in many different populations, but it has not been studied in Roma individuals so far. The aim of the study was to analyse the genotype in Roma patients with 21OHD and the prevalence of the disease in the Roma population of North Macedonia. Methods Molecular analysis of the nine most frequent CYP21A2 mutations in all known Roma patients with CAH in North Macedonia, relatives and healthy individuals of Roma ancestry, using the PCR/ACRS method. Results Ten Roma patients with 21OHD were identified, of which nine had the salt‐wasting and one had the simple virilizing form. Calculated incidence of 21OHD in the North Macedonian Roma population was 1:3375. Interestingly, 9/10 patients (90%) were homozygous for the In2G splicing mutation (293‐13A/C > G). Standard therapy with hydrocortisone and fludrocortisone had been introduced according to the guidelines. In 16 healthy relatives investigated for CYP21A2 mutations, heterozygosity for the In2G mutation was detected in 13/32 (40.6%) alleles. In 100 healthy Roma individuals, none related to the analysed families, no CYP21A2 mutations were detected. Conclusion The Roma population in North Macedonia had a very high incidence of classic 21OHD. Almost all patients had the severe salt‐wasting form and the In2G/In2G genotype.

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Section: Discussionmentioning

confidence: 61%

“…1 Khan et al found a high variety of mutations in patients with CAH in different Indian ethnicities, except in the Urdu ethnicity, where 8 out of 10 carried In2G mutation of which 5 were homozygous. 36,37 However, connection between the Roma and the Urdu populations remains to be explored. Especially.…”

Section: Discussionmentioning

confidence: 99%

First insights into the genetics of 21‐hydroxylase deficiency in the Roma population

Kočova

Anastasovska

Petlichkovski

et al. 2021

Clinical Endocrinology

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“…[ 12 13 31 32 ] In SV type, p.I172N mutation was found to be high and this trend was reported in many studies. [ 22 25 33 34 ] I172N is the only one mutation specifically associated with the SV form of the disease, and mutation of this hydrophobic residue to a polar residue results in an enzyme with approximately 1% or normal activity. [ 21 35 ] The frequency of p.P30L mutation was relatively high in our study, when compared with other studies.…”

Section: Discussionmentioning

confidence: 99%

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

Eunice¹,

Sharma²,

Kulshreshtha³

et al. 2012

Indian J Endocr Metab

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Context:Congenital adrenal hyperplasia (CAH) is one of the inborn errors of metabolic disorder inherited in an autosomal recessive manner caused by the defects in the steroid 21 hydroxylase CYP21A2 gene. We analyzed the genotype of 62 patients with classic CAH.Aims:To find out the underlying mutations of CYP21A2 gene.Settings and Design:Cohort of CAH patients.Materials and Methods:Sixty-two patients with CAH were recruited from the endocrine clinic at AIIMS. Electrochemiluminiscence method was used for estimating the levels of cortisol. Radioimmunoassay kit-based method was used for estimating the 17 OHP levels. Polymerase chain reaction amplification was done using specific primers to amply the CYP21A2 gene.Statistical Analysis Used:Statistical analysis was done by using Epi Info Version 3.5.1.2008.Results:Out of 62 patients, 50 were simple virilizers (SV) and 12 were salt wasters (SW). Fifty-six were females and six were males. Five 46, XX children were reared as males. Age at presentation varied from 8 months to 38 years. Molecular genetic analysis revealed that the highest number of patients harboured (In 2) IVS2-13 A/C > G (48%), followed by p.P30L (46%), p.Q318X (35%), (D 8 bp) deletion 8 bp (26%), p.I172N (26%), and p. R356W (20%) mutations.Conclusion:This is among the few studies to analyze the mutational spectrum of CYP21A2 gene in a large CAH cohort from India. Molecular diagnosis of CYP21A2 gene should be considered as part of the CAH evaluation to assess the risk of the patients/parents/siblings and to offer genetic counseling.

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“…One of the PND studies carried out on 24 pregnancies reported I2g mutation in 52 per cent and deletions in 22 per cent of the alleles 26 . Overall, I2g is the single most prevalent mutation reported from other ethnic populations as well as from Indian studies 24 27 28 .…”

Section: Discussionmentioning

confidence: 96%

Prenatal diagnosis of steroid 21-hydroxylase-deficient congenital adrenal hyperplasia

Dubey

Tardy²,

Chowdhury

et al. 2017

Indian Journal of Medical Research

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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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Ethnic disparity in 21-hydroxylase gene mutations identified in Pakistani congenital adrenal hyperplasia patients

Cited by 21 publications

References 13 publications

First insights into the genetics of 21‐hydroxylase deficiency in the Roma population

First insights into the genetics of 21‐hydroxylase deficiency in the Roma population

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

Prenatal diagnosis of steroid 21-hydroxylase-deficient congenital adrenal hyperplasia

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