Journal of Clinical Endocrinology & Metabolism, Vol 81, 1730-1735, Copyright © 1996 by Endocrine Society

ARTICLES

5 alpha-reductase-2 gene mutations in the Dominican Republic

LQ Cai, YS Zhu, MD Katz, C Herrera, J Baez, M DeFillo-Ricart, CH Shackleton and J Imperato-McGinley
Department of Medicine, New York Hospital-Cornell University Medical College, New York 10021, USA.

Male pseudohermaphroditism due to 5 alpha-reductase deficiency was clinically and biochemically described in a large Dominican kindred of 23 families with 38 affected subjects in 1974. Recently, the 5 alpha- reductase-2 gene defect in the large Dominican kindred was found to be due to a single base substitution of thymidine (TGG) for cytosine (CGG) on exon 5 of the 5 alpha-reductase-2 gene, causing a tryptophan replacement of arginine at amino acid 246 (R246W) of the enzyme. In the present report, affected subjects from four additional Dominican families were studied to determine whether they carried the same 5 alpha-reductase-2 gene defect as the large kindred, suggesting a common ancestry for the gene defect within this small country. Using single strand conformational polymorphism and DNA sequencing, two other mutations of the 5 alpha-reductase-2 gene were found in affected subjects from two of the four families. A point mutation on exon 2 of the 5 alpha-reductase-2 gene, in which substitution of adenine (GAC) for guanine (GGC) caused an aspartic acid replacement of glycine at amino acid 115 (G115D), was demonstrated in one of these families, and a substitution of adenine (AGT) for guanine (GGT) on exon 3 causing a serine replacement for glycine at amino acid 183 (G183S) was detected in the other family. Affected subjects from the two remaining families demonstrated the same exon 5 mutation of the 5 alpha-reductase-2 gene as previously detected in the large Dominican kindred. The phenotypic and biochemical characteristics of the male pseudohermaphrodites were similar regardless of the genetic defect, except that one affected subject (C-VI-2) with the same exon 5 mutation as the large Dominican kindred had much more facial and body hair. Thus, the identification of multiple mutations in the 5 alpha-reductase-2 gene in male pseudohermaphrodites from the Dominican Republic demonstrates a lack of common ancestry, as had been previously postulated.

This article has been cited by other articles:

				V. Sobel, B. Schwartz, Y.-S. Zhu, J. J. Cordero, and J. Imperato-McGinley Bone Mineral Density in the Complete Androgen Insensitivity and 5{alpha}-Reductase-2 Deficiency Syndromes J. Clin. Endocrinol. Metab., August 1, 2006; 91(8): 3017 - 3023. [Abstract] [Full Text] [PDF]

				J. K. Lee, Y.-S. Zhu, J. J. Cordero, L.-Q. Cai, I. Labour, C. Herrera, and J. Imperato-McGinley Long-Term Growth Hormone Therapy in Adulthood Results in Significant Linear Growth in Siblings with a PROP-1 Gene Mutation J. Clin. Endocrinol. Metab., October 1, 2004; 89(10): 4850 - 4856. [Abstract] [Full Text] [PDF]

				M. Fernandez-Cancio, M. Nistal, R. Gracia, M. A. Molina, J. A. Tovar, C. Esteban, A. Carrascosa, and L. Audi Compound Heterozygous Mutations in the SRD5A2 Gene Exon 4 in a Male Pseudohermaphrodite Patient of Chinese Origin J Androl, May 1, 2004; 25(3): 412 - 416. [Abstract] [Full Text] [PDF]

				A. W. F. T. Toorians, S. Kelleher, L. J. Gooren, M. Jimenez, and D. J. Handelsman Estimating the Contribution of the Prostate to Blood Dihydrotestosterone J. Clin. Endocrinol. Metab., November 1, 2003; 88(11): 5207 - 5211. [Abstract] [Full Text] [PDF]

				Y.-S. Zhu, L.-Q. Cai, J. J. Cordero, W. J. Canovatchel, M. D. Katz, and J. Imperato-McGinley A Novel Mutation in the CAG Triplet Region of Exon 1 of Androgen Receptor Gene Causes Complete Androgen Insensitivity Syndrome in a Large Kindred J. Clin. Endocrinol. Metab., May 1, 1999; 84(5): 1590 - 1594. [Abstract] [Full Text]

				S. S. Stavrou, Y.-S. Zhu, L.-Q. Cai, M. D. Katz, C. Herrera, M. DeFillo-Ricart, and J. Imperato-McGinley A Novel Mutation of the Human Luteinizing Hormone Receptor in 46XY and 46XX Sisters J. Clin. Endocrinol. Metab., June 1, 1998; 83(6): 2091 - 2098. [Abstract] [Full Text]

				S. Can, Y.-S. Zhu, L.-Q. Cai, Q. Ling, M. D. Katz, S. Akgun, C. H. L. Shackleton, and J. Imperato-McGinley The Identification of 5{alpha}-Reductase-2 and 17{beta}-Hydroxysteroid Dehydrogenase-3 Gene Defects in Male Pseudohermaphrodites from a Turkish Kindred J. Clin. Endocrinol. Metab., February 1, 1998; 83(2): 560 - 569. [Abstract] [Full Text]

				M. D. Katz, I. Kligman, L.-Q. Cai, Y.-S. Zhu, C. M. Fratianni, I. Zervoudakis, Z. Rosenwaks, and J. Imperato-McGinley Paternity by Intrauterine Insemination with Sperm from a Man with 5{alpha}-Reductase-2 Deficiency N. Engl. J. Med., April 3, 1997; 336(14): 994 - 998. [Full Text] [PDF]