This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Merke, D. P. Articles by Cutler, G. B. Search for Related Content PubMed PubMed Citation Articles by Merke, D. P. Articles by Cutler, G. B., Jr.

Novel CYP11B1 Mutations in Congenital Adrenal Hyperplasia due to Steroid 11ß-Hydroxylase Deficiency

Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892

Address all correspondence and requests for reprints to: Deborah P. Merke, M.D., Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Building 10, Room 10N262, 10 Center Drive, MSC 1862, Bethesda, Maryland 20892-1862.

The second most common cause of congenital adrenal hyperplasia is 11ß-hydroxylase deficiency, an autosomal recessive disorder. We performed genetic analysis of CYP11B1, the gene encoding steroid 11ß-hydroxylase, in three patients with classic 11ß-hydroxylase deficiency. Herein we describe the first splice donor site mutation, a new nonsense mutation, and a new missense mutation in this disorder. An African-American patient was found to be a compound heterozygote for a codon 318+1GA substitution at the 5'-splice donor site of intron 5, in combination with Q356X, a nonsense mutation previously reported in an African-American patient. A Caucasian patient was found to be a compound heterozygote with a novel missense mutation, T318R, in combination with a previously reported 28-bp deletion in exon 2. A different mutation at codon 318 (T318M) has been described previously. A Caucasian patient was heterozygous for a novel nonsense mutation (Q19X) in exon 2. The second mutation was not identified in this patient. Multiple apparent polymorphisms were also observed. Two of these polymorphisms in CYP11B1 represent sequences from CYP11B2, suggesting that gene conversion may have occurred. In summary, we have identified three novel mutations and two previously reported mutations in CYP11B1 patients with 11ß-hydroxylase deficiency. Our data suggest the presence of a mutational hot spot at codon 318 of CYP11B1, and the possibility of a founder effect in frequently identified mutations.

This article has been cited by other articles:

				N. Krone, Y. Grischuk, M. Muller, R. E. Volk, J. Grotzinger, P.-M. Holterhus, W. G. Sippell, and F. G. Riepe Analyzing the Functional and Structural Consequences of Two Point Mutations (P94L and A368D) in the CYP11B1 Gene Causing Congenital Adrenal Hyperplasia Resulting from 11-Hydroxylase Deficiency J. Clin. Endocrinol. Metab., July 1, 2006; 91(7): 2682 - 2688. [Abstract] [Full Text] [PDF]

				A. Grigorescu Sido, M. M. Weber, P. Grigorescu Sido, S. Clausmeyer, U. Heinrich, and E. Schulze 21-Hydroxylase and 11{beta}-Hydroxylase Mutations in Romanian Patients with Classic Congenital Adrenal Hyperplasia J. Clin. Endocrinol. Metab., October 1, 2005; 90(10): 5769 - 5773. [Abstract] [Full Text] [PDF]

				T. Paperna, R. Gershoni-Baruch, K. Badarneh, L. Kasinetz, and Z. Hochberg Mutations in CYP11B1 and Congenital Adrenal Hyperplasia in Moroccan Jews J. Clin. Endocrinol. Metab., September 1, 2005; 90(9): 5463 - 5465. [Abstract] [Full Text] [PDF]

				N. Krone, F. G. Riepe, D. Gotze, E. Korsch, M. Rister, J. Commentz, C.-J. Partsch, J. Grotzinger, M. Peter, and W. G. Sippell Congenital Adrenal Hyperplasia Due to 11-Hydroxylase Deficiency: Functional Characterization of Two Novel Point Mutations and a Three-Base Pair Deletion in the CYP11B1 Gene J. Clin. Endocrinol. Metab., June 1, 2005; 90(6): 3724 - 3730. [Abstract] [Full Text] [PDF]

				M. Hampf, N. T. N. Dao, N. T. Hoan, and R. Bernhardt Unequal Crossing-Over between Aldosterone Synthase and 11{beta}-Hydroxylase Genes Causes Congenital Adrenal Hyperplasia J. Clin. Endocrinol. Metab., September 1, 2001; 86(9): 4445 - 4452. [Abstract] [Full Text] [PDF]

				O. Chabre, S. Portrat-Doyen, P. Chaffanjon, J. Vivier, P. Liakos, F. Labat-Moleur, E. Chambaz, Y. Morel, and G. Defaye Bilateral Laparoscopic Adrenalectomy for Congenital Adrenal Hyperplasia with Severe Hypertension, Resulting from Two Novel Mutations in Splice Donor Sites of CYP11B1 J. Clin. Endocrinol. Metab., November 1, 2000; 85(11): 4060 - 4068. [Abstract] [Full Text]

				S. Kitanaka, A. Murayama, T. Sakaki, K. Inouye, Y. Seino, S. Fukumoto, M. Shima, S. Yukizane, M. Takayanagi, H. Niimi, et al. No Enzyme Activity of 25-Hydroxyvitamin D3 1{alpha}-Hydroxylase Gene Product in Pseudovitamin D Deficiency Rickets, Including That with Mild Clinical Manifestation J. Clin. Endocrinol. Metab., November 1, 1999; 84(11): 4111 - 4117. [Abstract] [Full Text]

				B. I. Cerame, R. S. Newfield, L. Pascoe, K. M. Curnow, S. Nimkarn, T. F. Roe, M. I. New, and R. C. Wilson Prenatal Diagnosis and Treatment of 11{beta}-Hydroxylase Deficiency Congenital Adrenal Hyperplasia Resulting in Normal Female Genitalia J. Clin. Endocrinol. Metab., September 1, 1999; 84(9): 3129 - 3134. [Abstract] [Full Text]

				P. P. Feuillan, J. V. Jones, K. Barnes, K. Oerter-Klein, and G. B. Cutler Jr. Reproductive Axis after Discontinuation of Gonadotropin-Releasing Hormone Analog Treatment of Girls with Precocious Puberty: Long Term Follow-Up Comparing Girls with Hypothalamic Hamartoma to Those with Idiopathic Precocious Puberty J. Clin. Endocrinol. Metab., January 1, 1999; 84(1): 44 - 49. [Abstract] [Full Text]