Tags

Type your tag names separated by a space and hit enter

Mutational characterization of congenital adrenal hyperplasia due to 21-hydroxylase deficiency in Malaysia.
J Endocrinol Invest. 2013 Jun; 36(6):366-74.JE

Abstract

BACKGROUND AND AIM

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) is a common autosomal recessive disorder. Our objective was to identify the 21-hydroxylase active gene, CYP21A2 mutations in Malaysian 21-OHD patients using different techniques.

MATERIALS AND METHODS

Blood samples were obtained from 97 Malaysian 21-OHD patients, which included 40 siblings from 19 families. We used various techniques which include restriction enzyme digestion, Southern blot, multiple ligation-dependent probe amplification (MLPA) and sequencing to elucidate CYP21A2 mutations.

RESULTS

Homozygous and compound heterozygous mutations were identified in 95 of the 97 patients (98%). Deletions of CYP21A2 were found in 43 patients (44.3%). Deletions identified in CYP21A2 gene were the usual 30-kb deletion comprising 3'UTR CYP21A1P, C4B and 5'CYP21A2, complete deletion of CYP21A2 gene, deletion in exons 1-3, exons 1-6 and exons 1-8 of CYP21A2. The common mutations identified in CYP21A2 gene were deletion/conversion (22.6%), p.R356W (22%), IVS2-13A/C>G (21.3%), p.I172N (5.3%), p.Q318X (5.3%), and p.P30L (1.03%). This is the first report of the mutation frequency in CYP21A2 gene among the Malay ethnic group. Two novel mutations, c.Y97insT and p.L345P were identified in our patients. Our results show good phenotype-genotype correlation in most of the cases, although clinical variations were identified in some patients.

CONCLUSIONS

The study has found various mutations including deletions in CYP21A2 gene in Malaysian patients with 21-hydroxylase deficiency using the MLPA technique that is being widely used in present laboratory settings.

Authors+Show Affiliations

Molecular Pathology Unit, Institute for Medical Research, Jln Pahang, Kuala Lumpur, Malaysia. pauline@imr.gov.myNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23027774

Citation

Balraj, P, et al. "Mutational Characterization of Congenital Adrenal Hyperplasia Due to 21-hydroxylase Deficiency in Malaysia." Journal of Endocrinological Investigation, vol. 36, no. 6, 2013, pp. 366-74.
Balraj P, Lim PG, Sidek H, et al. Mutational characterization of congenital adrenal hyperplasia due to 21-hydroxylase deficiency in Malaysia. J Endocrinol Invest. 2013;36(6):366-74.
Balraj, P., Lim, P. G., Sidek, H., Wu, L. L., & Khoo, A. S. (2013). Mutational characterization of congenital adrenal hyperplasia due to 21-hydroxylase deficiency in Malaysia. Journal of Endocrinological Investigation, 36(6), 366-74. https://doi.org/10.3275/8648
Balraj P, et al. Mutational Characterization of Congenital Adrenal Hyperplasia Due to 21-hydroxylase Deficiency in Malaysia. J Endocrinol Invest. 2013;36(6):366-74. PubMed PMID: 23027774.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mutational characterization of congenital adrenal hyperplasia due to 21-hydroxylase deficiency in Malaysia. AU - Balraj,P, AU - Lim,P G, AU - Sidek,H, AU - Wu,L L, AU - Khoo,A S B, Y1 - 2012/10/01/ PY - 2012/10/3/entrez PY - 2012/10/3/pubmed PY - 2013/11/20/medline SP - 366 EP - 74 JF - Journal of endocrinological investigation JO - J Endocrinol Invest VL - 36 IS - 6 N2 - BACKGROUND AND AIM: Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) is a common autosomal recessive disorder. Our objective was to identify the 21-hydroxylase active gene, CYP21A2 mutations in Malaysian 21-OHD patients using different techniques. MATERIALS AND METHODS: Blood samples were obtained from 97 Malaysian 21-OHD patients, which included 40 siblings from 19 families. We used various techniques which include restriction enzyme digestion, Southern blot, multiple ligation-dependent probe amplification (MLPA) and sequencing to elucidate CYP21A2 mutations. RESULTS: Homozygous and compound heterozygous mutations were identified in 95 of the 97 patients (98%). Deletions of CYP21A2 were found in 43 patients (44.3%). Deletions identified in CYP21A2 gene were the usual 30-kb deletion comprising 3'UTR CYP21A1P, C4B and 5'CYP21A2, complete deletion of CYP21A2 gene, deletion in exons 1-3, exons 1-6 and exons 1-8 of CYP21A2. The common mutations identified in CYP21A2 gene were deletion/conversion (22.6%), p.R356W (22%), IVS2-13A/C>G (21.3%), p.I172N (5.3%), p.Q318X (5.3%), and p.P30L (1.03%). This is the first report of the mutation frequency in CYP21A2 gene among the Malay ethnic group. Two novel mutations, c.Y97insT and p.L345P were identified in our patients. Our results show good phenotype-genotype correlation in most of the cases, although clinical variations were identified in some patients. CONCLUSIONS: The study has found various mutations including deletions in CYP21A2 gene in Malaysian patients with 21-hydroxylase deficiency using the MLPA technique that is being widely used in present laboratory settings. SN - 1720-8386 UR - https://www.unboundmedicine.com/medline/citation/23027774/Mutational_characterization_of_congenital_adrenal_hyperplasia_due_to_21_hydroxylase_deficiency_in_Malaysia_ L2 - https://link.springer.com/article/10.3275/8648 DB - PRIME DP - Unbound Medicine ER -