XX True Hermaphroditism in Southern African Blacks - david page ...

More documents

Recommendations

Info

XX True Hermaphroditism52.3.4. 5.NdeboNdb? ? I ? ?ieee hob.? bV b? i2FiIwAn(17. 8.i~~~~~~1930 1944Pod!i 1)~~~. ? Zul I_8 1970 19n 1975 19911957 591 1963 1977 /IX b ? b. ? b ?.11.68 b666d6To aTZul swanalTawanaTr.17- ? ? 1943 19.t 9.J... .19.....111 969 1973 1977 ig73 1974 1976 1984X_ d:3m* * probands with sexual ambiguity, reared as males or females - all are xX true hermaphrodites.0{1ONo known consanguinity between parents; distantly related maternal grandparents of proband in family 5 - degree of consanguinity unknown.Ql Males and females with normal sexual development; )O family member of unknown sex, but no known history of sexual anomalies.2t I2 Adults with no offspring - cause unknown; Hi proband died before a blood specimen for DNA studies could be obtained.Adults who died of unknown causes;. '3 stillbirths, neonatal. infant and childhood deaths of unknown causes; J miscarriages.Q3 Paternal first cousin of proband in family 2, who had "difficulties in holding his water"; paternal uncle of proband in family 5. who has a mental illness.cJ)bPhenotypically normal twin girls (7 mono or dizygotic);A twins of unknown sex, but no known history of sexual anomalies.Figure IPedigrees of 11 families with XX true hermaphroditismhospitals, and academic referral hospitals. These 183cases were reviewed so as to identify histologicallyproven true hermaphrodites. Only those cases inwhich both testicular tissue (with distinct tubules)and ovarian tissue (containing follicles) were histologicallydemonstrable were classed as true hermaphrodites.Gonadal distribution in the proven cases wasclassified according to the criteria established in 1935by Hinman (quoted in Van Niekerk 1974).Pedigrees of 11 black families with proven caseswere compiled (fig. 1), and a structured interviewposed questions designed to establish a possible geneticor environmental etiology.Chromosome StudiesMetaphases were derived from 72-h phytohemagglutinin-stimulatedand methotrexate-synchronizedperipheral blood cultures (Yunis 1976). Fibroblastcultures were established from skin and/or gonadalbiopsies in six of the patients. Giemsa (GTG) and
6Ramsay et al.Table IY Chromosome-specific ProbesY-specificY-ChromosomeFragmentDeletion Restriction SizeProbe Intervala Enzyme (kb) ReferencepDP132 (DXYS23) ........ 1 TaqI 4.4 D. C. Page, unpublished resultspDP61 (DXYS8) .2 TaqI 2.1 or 2.6 Geldwerth et al. 1985 ;b D. C. Page, unpublished resultspDP105 (DYZ4)D. C. Page, unpublished resultspDP15/A .3 TaqI 2.3pDP105/B .6 TaqI 5.1pDP31 (DXYS1) .4A TaqI 15 Page et al. 1984pDP97 (DYZ3) .4B EcoRI 5.5 Wolfe et al. 1985;C D. C. Page, unpublished resultspY431-HinfA (DYZ2) 7 EcoRI Several K. Smith, personal communicationa Source: Page (1986) and Vergnaud et al. (1986).bProbe derived from plasmid 115.c Probe derived from cosmid Y 97.quinacrine (QFQ) banding of the chromosomes wasperformed. In some cases, buccal smears were examinedfor X and Y chromatin.Molecular Hybridization StudiesPeripheral blood samples were obtained from 10histologically proven black XX hermaphrodites andfrom the majority of their mothers and fathers. DNAwas extracted according to the method of Sykes(1983). DNA from the probands and parents wasdigested with either EcoRI or TaqI, electrophoresedin 0.8% agarose, transferred to nitrocellulose or nylonmembranes (Southern 1975), and hybridizedwith the six Y chromosome-specific DNA probesdescribed in table 1. Hybridization studies usingprobes that detect X-linked RFLPs were performedon five complete families (father, mother, and proband)in order to test paternal and maternal inheritanceof the two X chromosomes in the proband(Page and de la Chapelle 1984). Probes L1.28, RC8(Davies et al. 1983), pDP31 (Page et al. 1984), and St14 (Oberle et al. 1985) were used for this purpose.ResultsOf 152 blacks with ambiguous genitalia and a46,XX karyotype, the diagnosis of true hermaphroditismwas proved in all 38 who were histologicallyinvestigated. Of 31 whites with ambiguous genitaliaand a 46,XX karyotype, none were shown to be truehermaphrodites on histological examination.The gonadal distribution of ovarian and testiculartissue in the 38 proven black hermaphrodites isshown in table 2. Testicular tissue was identified onthe right side (32 cases) far more frequently than onthe left side (15 cases).Clinical DataClinical data are summarized in table 3. Of 38patients studied, 16 were
Page 1: Am. J. Hum. Genet. 43:004-013, 1988
Page 5 and 6: 8whom had recognizable (though ofte
Page 7 and 8: 10Clinical FindingsThe anomalies of
Page 9 and 10: 12 Ramsay et al.cluded in view of t

XX True Hermaphroditism in Southern African Blacks - david page ...

Create successful ePaper yourself

Delete template?

Save as template?