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Erroneous prenatal diagnosis of congenital adrenal hyperplasia owing to a duplication of the CYP21A2 gene.
J Perinatol. 2013 Jan; 33(1):76-8.JP

Abstract

Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder where steroidogenesis in the adrenal cortex is impaired. The most common form is caused by 21-hydroxylase deficiency (21OHD). Classical 21OHD is characterized by glucocorticoid and mineralocorticoid deficiency and by overproduction of adrenal androgens. The diagnosis rests on biochemical and genetic analyses. In families with history of CAH, prenatal genetic diagnosis is offered. We herein present a case of an infant whose parents were identified to carry mutations on the CYP21A2 gene. The fetal DNA analysis demonstrated that the fetus carried a paternal exon 8 (Q318X) mutation and a maternal exon 8 (R356X) mutation. The fetus was presumed to be affected with CAH, yet his clinical presentation at birth was not consistent with the diagnosis. Repeated genetic analysis identified a paternal CYP21A2 gene duplication with Q318X mutation on one copy of CYP21A2. We conclude that a duplication of the CYP21A2 gene should be suspected when clinical and hormonal findings do not support the genetic diagnosis. Furthermore, because individuals with Q318X mutation frequently have a duplication of the CYP21A2 gene, when Q318X is detected, it is important to distinguish the severe point mutation in single gene copy alleles from the non-deficient variant in gene-duplicated alleles.

Authors+Show Affiliations

Department of Pediatric Endocrinology, Adrenal Steroid Disorders Program, Mount Sinai School of Medicine, New York, NY 10029, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Case Reports
Journal Article

Language

eng

PubMed ID

23269230

Citation

Lekarev, O, et al. "Erroneous Prenatal Diagnosis of Congenital Adrenal Hyperplasia Owing to a Duplication of the CYP21A2 Gene." Journal of Perinatology : Official Journal of the California Perinatal Association, vol. 33, no. 1, 2013, pp. 76-8.
Lekarev O, Tafuri K, Lane AH, et al. Erroneous prenatal diagnosis of congenital adrenal hyperplasia owing to a duplication of the CYP21A2 gene. J Perinatol. 2013;33(1):76-8.
Lekarev, O., Tafuri, K., Lane, A. H., Zhu, G., Nakamoto, J. M., Buller-Burckle, A. M., Wilson, T. A., & New, M. I. (2013). Erroneous prenatal diagnosis of congenital adrenal hyperplasia owing to a duplication of the CYP21A2 gene. Journal of Perinatology : Official Journal of the California Perinatal Association, 33(1), 76-8. https://doi.org/10.1038/jp.2012.5
Lekarev O, et al. Erroneous Prenatal Diagnosis of Congenital Adrenal Hyperplasia Owing to a Duplication of the CYP21A2 Gene. J Perinatol. 2013;33(1):76-8. PubMed PMID: 23269230.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Erroneous prenatal diagnosis of congenital adrenal hyperplasia owing to a duplication of the CYP21A2 gene. AU - Lekarev,O, AU - Tafuri,K, AU - Lane,A H, AU - Zhu,G, AU - Nakamoto,J M, AU - Buller-Burckle,A M, AU - Wilson,T A, AU - New,M I, PY - 2012/12/28/entrez PY - 2012/12/28/pubmed PY - 2013/6/25/medline SP - 76 EP - 8 JF - Journal of perinatology : official journal of the California Perinatal Association JO - J Perinatol VL - 33 IS - 1 N2 - Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder where steroidogenesis in the adrenal cortex is impaired. The most common form is caused by 21-hydroxylase deficiency (21OHD). Classical 21OHD is characterized by glucocorticoid and mineralocorticoid deficiency and by overproduction of adrenal androgens. The diagnosis rests on biochemical and genetic analyses. In families with history of CAH, prenatal genetic diagnosis is offered. We herein present a case of an infant whose parents were identified to carry mutations on the CYP21A2 gene. The fetal DNA analysis demonstrated that the fetus carried a paternal exon 8 (Q318X) mutation and a maternal exon 8 (R356X) mutation. The fetus was presumed to be affected with CAH, yet his clinical presentation at birth was not consistent with the diagnosis. Repeated genetic analysis identified a paternal CYP21A2 gene duplication with Q318X mutation on one copy of CYP21A2. We conclude that a duplication of the CYP21A2 gene should be suspected when clinical and hormonal findings do not support the genetic diagnosis. Furthermore, because individuals with Q318X mutation frequently have a duplication of the CYP21A2 gene, when Q318X is detected, it is important to distinguish the severe point mutation in single gene copy alleles from the non-deficient variant in gene-duplicated alleles. SN - 1476-5543 UR - https://www.unboundmedicine.com/medline/citation/23269230/Erroneous_prenatal_diagnosis_of_congenital_adrenal_hyperplasia_owing_to_a_duplication_of_the_CYP21A2_gene_ L2 - https://doi.org/10.1038/jp.2012.5 DB - PRIME DP - Unbound Medicine ER -