Journal of Medical Sciences1682-44741812-5727Asian Network for Scientific Information10.3923/jms.2002.158.164HafezM. El-ZinyM. AhmedA. H. HawasS. Abou-HashemE. HegaziA. BaghdadyL. HafezM. M. 4200224The objective of this investigation was to study the genetic susceptibility in pubertal females having hyperandrogenic manifestations without an evident cause. This study included 31 pubertal females, presented by hirsutism, acne and androgenic alopecia in various combinations. Exclusion criteria were ovarian and suprarenal tumors, classical congenital adrenal hyperplasia, ambiguous genitalia or receiving drugs that may give androgenic manifestations. Parents and sibs of the multicase families were included. In addition 40 normal females of matched age were taken as control group. Pelvic ultrasonography was done and blood samples were withdrawn (9 a.m.) in the fifth day of menstrual cycle for estimation of serum cortisol, dehydroepiandrosterone sulfate, 17-hydroxyprogesterone, testosterone, estrone-2 (E2), luteinizing hormone (LH) and follicle stimulating hormone (FSH). For all the parents and female sibs, affected and unaffected, of the multicase families, HLA class I (A and B) and CLASS II (DR and DQ) were determined in addition to the 40 control female. Patients were enrolled into 3 groups; Group 1 (G1) included 11 cases with normal hormonal profile. Out of them 7 have female sib(s) affected (7 multicase families) with hormonal levels in the normal range. Group 2 (G2) included cases with increased hormones and LH/FSH ratio <2. Out of them 8 were members of multicase families with the same hormonal profile. Group 3 (G3) included cases with increased hormones and LH/FSH ratio >2. Non of them has affected female sib. The genetic analysis included HLA-haplotype concordance, lod score for linkage and identity by descent. The results revealed that in G2 the levels of cortisol and E2 were significantly low (P<0.05). In G3 only cortisol was significantly low (P<0.05) while other parameters were significantly high (P<0.05). HLA-antigens and alleles of patients revealed significantly different frequencies from control. The values of HLA haplotype concordance in G1 and G2 were different from the expected (P<0.001). Lod scores for linkage showed that in G2 the observations fit the recessive model of linkage (Z=4.53, X2 = 3.24). IBD analysis in G1 fits dominant model (P = 0.36) and in G2 fits the recessive model (P = 0.64). In conclusion the hyperandrogenic manifestations in G1 are due to dominant inherited hypersensitivity to hormones. G2 and G3 may result from dyshormonogenesis due to recessive gene(s) leading to non-classical congenital adrenal hyperplasia or polycystic ovary (PCO) syndrome.]]>Ambrosi, B., T. Re, E. Passini, D. Bochicchio and R. Ferrario,199619204209Avivi, I., S. Linn, S. Pollack, Z. Blumenfeld and O. Gideoni,199666557563Azziz, R., G. Wells, H.A. Zacur and R.T. Acton,19917313271331Azziz, R., D. Dewailly and D. Owerbach,199478810815Azziz, R., E. Carmina and M.E. Sawaya,200021347362Chrousos, G.P., D.L. Loriaux, D.L. Mann and G.B. Cutler,198296143148Conway, G.S., J.W. Honour and H.S. Jacobs,198930459470Deplewski, D. and R.L. Rosenfield,200021363392Dewailly, D., M. Vantyghem-Haudiquet, C. Sainsard, J. Buvat and J.P. Cappoen et al.,198663418423Ehrmann, D., R. Rosenfield and R. Barnes,1992327157162Elias, L.L., J.C. Voltarelli and A.C. Moreira,199326177189Emans, S.J., E. Grace, E. Fleischnick, M.J. Mansfield and J.F. Crigler,198372690695Franks, S.,19893187120Kahsar-Miller, M. and R. Azziz,199969261268Kim, M., R.L. Rosenfield, A. Hosseinian and H. Schneir,1979134445452Lee, P.A., Z. Rosenwaks, M.D. Urban, C.J. Migeon and W.D. Bias,198255866871McKenna, T.,1988318558562Migeon, C.J., Z. Rosenwaks, P.A. Lee, M.D. Urban and W.D. Bias, 198051647649Miller, W.L.,199744375395Morton, N.E.,198333224249Pollack, M.S., B. Keenan, E.T. Christiansen, T.J. Cobain, R.L. Dawkins and G. Clayton,198638688698Ober, C., O., S. Weil, T. Steck, C. Billstrand, S. Levrant and R. Barnes,199216718031806Olerup, O. and H. Detterquist,199239225235Olerup, O., A. Aldener and A. Fogdell,199341119134Rosenfield, R.L.,198615341362Speek, M., F. barry and W.L. miller,1996517491758Speiser, P.W., B. Dupont, P. Rubinstein, A. Piazza, A. Kastelan and M.I. New,198537650667Vottero, A., C.A. Stratakis, L. Ghizzoni, C.A. Longui, M. Karl and G.P. Chrousos,19998410911995Yen, S.,198012177208Zhang, L., H. Rodriguez, S. Ohno and W.L. Miller,1995921061910623Armitage, P.,19895th Edn.,