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CYP21A2 gene mutations in congenital adrenal hyperplasia: genotype-phenotype correlation in Turkish children.
J Clin Res Pediatr Endocrinol. 2009; 1(3):116-28.JC

Abstract

BACKGROUND

Congenital adrenal hyperplasia (CAH) due 21-hydroxylase deficiency (21-OHD) is a common autosomal recessive disorder. It is caused by defects in the CYP21A2 gene.

OBJECTIVE

Our aim was to determine the frequency of common gene mutations and to evaluate genotype-phenotype correlations in Turkish 21-OHD patients.

METHODS

Molecular analysis of the CYP21A2 gene was performed for the detection of the eight most common point mutations [p.P30L, IVS2-13C>G (IVS-2), p.I172N, exon 6 mutation cluster (p.I236N, p.V237E, p.M239K), p.V281L, p.Q318X, p.R356W, 8-bp-deletion], of large deletion and conversion by southern blotting, allele specific semi-quantitative PCR/enzyme restriction method and sequencing, in 56 patients with 21-OHD, from 52 families.

RESULTS

Disease-causing mutations were identified in 77 out of 91 alleles (84.6%) of the patients. Mutations were found in 34 of 43 alleles (79.1%) in salt wasting (SW; n=26), 32 of 36 alleles (88.8%) in simple virilizing (SV; n=24) and 11 of 12 alleles (91.6%) in non-classical (NC; n=6) form of CAH. The most frequent mutations were IVS-2 (22.0%), large conversion (14.3%), p.I172N (9.9%) p.R356W (8.8%), and large deletion (6.6%). In the SW form, the most frequent genotypes were homozygous for IVS-2 (11.5%) and homozygous for large conversion of the gene (11.5%). In the SV form, the most frequent genotype was homozygous for IVS-2 (20%), followed by compound heterozygous for p.I172N/8-bp del (10%). Homozygous for p.V281L (16.7%) was most common in NC. In most cases there was good correlation between genotype and phenotype. In the SW and NC forms, genotypes of all the patients correlated with their phenotypes.

CONCLUSIONS

This is the first comprehensive study on the molecular basis of CAH patients in the Turkish population. Based on these results, we propose a modified screening strategy to facilitate molecular testing of CAH patients in our population.

Authors+Show Affiliations

Istanbul University, Istanbul Faculty of Medicine, Department of Pediatrics, Pediatric Endocrinology Unit, Istanbul, Turkey. firdevsbas@superonline.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

21274396

Citation

Baş, Firdevs, et al. "CYP21A2 Gene Mutations in Congenital Adrenal Hyperplasia: Genotype-phenotype Correlation in Turkish Children." Journal of Clinical Research in Pediatric Endocrinology, vol. 1, no. 3, 2009, pp. 116-28.
Baş F, Kayserili H, Darendeliler F, et al. CYP21A2 gene mutations in congenital adrenal hyperplasia: genotype-phenotype correlation in Turkish children. J Clin Res Pediatr Endocrinol. 2009;1(3):116-28.
Baş, F., Kayserili, H., Darendeliler, F., Uyguner, O., Günöz, H., Yüksel Apak, M., Atalar, F., Bundak, R., Wilson, R. C., New, M. I., Wollnik, B., & Saka, N. (2009). CYP21A2 gene mutations in congenital adrenal hyperplasia: genotype-phenotype correlation in Turkish children. Journal of Clinical Research in Pediatric Endocrinology, 1(3), 116-28. https://doi.org/10.4008/jcrpe.v1i3.49
Baş F, et al. CYP21A2 Gene Mutations in Congenital Adrenal Hyperplasia: Genotype-phenotype Correlation in Turkish Children. J Clin Res Pediatr Endocrinol. 2009;1(3):116-28. PubMed PMID: 21274396.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - CYP21A2 gene mutations in congenital adrenal hyperplasia: genotype-phenotype correlation in Turkish children. AU - Baş,Firdevs, AU - Kayserili,Hülya, AU - Darendeliler,Feyza, AU - Uyguner,Oya, AU - Günöz,Hülya, AU - Yüksel Apak,Memnune, AU - Atalar,Fatmahan, AU - Bundak,Rüveyde, AU - Wilson,Robert C, AU - New,Maria I, AU - Wollnik,Bernd, AU - Saka,Nurçin, Y1 - 2009/02/02/ PY - 2009/02/09/received PY - 2009/02/23/accepted PY - 2011/1/29/entrez PY - 2009/3/1/pubmed PY - 2011/12/16/medline KW - 21−hydroxylase KW - congenital adrenal hyperplasia SP - 116 EP - 28 JF - Journal of clinical research in pediatric endocrinology JO - J Clin Res Pediatr Endocrinol VL - 1 IS - 3 N2 - BACKGROUND: Congenital adrenal hyperplasia (CAH) due 21-hydroxylase deficiency (21-OHD) is a common autosomal recessive disorder. It is caused by defects in the CYP21A2 gene. OBJECTIVE: Our aim was to determine the frequency of common gene mutations and to evaluate genotype-phenotype correlations in Turkish 21-OHD patients. METHODS: Molecular analysis of the CYP21A2 gene was performed for the detection of the eight most common point mutations [p.P30L, IVS2-13C>G (IVS-2), p.I172N, exon 6 mutation cluster (p.I236N, p.V237E, p.M239K), p.V281L, p.Q318X, p.R356W, 8-bp-deletion], of large deletion and conversion by southern blotting, allele specific semi-quantitative PCR/enzyme restriction method and sequencing, in 56 patients with 21-OHD, from 52 families. RESULTS: Disease-causing mutations were identified in 77 out of 91 alleles (84.6%) of the patients. Mutations were found in 34 of 43 alleles (79.1%) in salt wasting (SW; n=26), 32 of 36 alleles (88.8%) in simple virilizing (SV; n=24) and 11 of 12 alleles (91.6%) in non-classical (NC; n=6) form of CAH. The most frequent mutations were IVS-2 (22.0%), large conversion (14.3%), p.I172N (9.9%) p.R356W (8.8%), and large deletion (6.6%). In the SW form, the most frequent genotypes were homozygous for IVS-2 (11.5%) and homozygous for large conversion of the gene (11.5%). In the SV form, the most frequent genotype was homozygous for IVS-2 (20%), followed by compound heterozygous for p.I172N/8-bp del (10%). Homozygous for p.V281L (16.7%) was most common in NC. In most cases there was good correlation between genotype and phenotype. In the SW and NC forms, genotypes of all the patients correlated with their phenotypes. CONCLUSIONS: This is the first comprehensive study on the molecular basis of CAH patients in the Turkish population. Based on these results, we propose a modified screening strategy to facilitate molecular testing of CAH patients in our population. SN - 1308-5735 UR - https://www.unboundmedicine.com/medline/citation/21274396/CYP21A2_gene_mutations_in_congenital_adrenal_hyperplasia:_genotype_phenotype_correlation_in_Turkish_children_ L2 - https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21274396/ DB - PRIME DP - Unbound Medicine ER -