Extended pedigree with multiple cases of XX sex reversal in the absence of SRY and of a mutation at the SOX9 locus

Jin, Woo JungLeipoldt, MichaelBausch, ElkeScherer, Gerd2022-09-122022-09-122007Temel, Ş. G. vd. (2007). "Extended pedigree with multiple cases of XX sex reversal in the absence of SRY and of a mutation at the SOX9 locus". Sexual Development, 1(1), 24-34.16615433https://doi.org/10.1159/000096236https://www.karger.com/Article/FullText/96236http://hdl.handle.net/11452/28649It is well established that testicular differentiation of the human embryonic gonad depends on the action of the Y-chromosomal gene SRY. However, exceptional cases such as SRY-negative cases of 46,XX testicular disorder of sexual development (DSD), and of 46,XX ovotesticular DSD document that testicular tissue can develop in the absence of the SRY gene. These SRY-negative XX sex reversal cases are very rare and usually sporadic, but a few familial cases have been reported. We present a large, consanguineous family with nine affected individuals with phenotypes ranging from 46, XX testicular DSD to 46, XX ovotesticular DSD, with predominance of male characteristics. Absence of SRY in peripheral blood was documented by fluorescence in situ hybridization (FISH) and PCR analysis in all nine affected individuals, and by FISH analysis on gonadal sections with testicular tissue in four affected individuals. By quantitative PCR, a duplication of the SOX9 gene was excluded. In addition, as linkage analysis showed that the nine affected members of the family do not share a common SOX9 haplotype, any mutation at the SOX9 locus could be ruled out. Together, these findings implicate a mutation at a sex-determining locus other than SRY and SOX9 as the cause for the XX sex reversal trait in this family.eninfo:eu-repo/semantics/openAccessSOX9True Hermaphrodites46, XX ovotesticular DSD46, XX testicular DSDSex determinationSex differentiationSex reversalSRYCampomelic dysplasia46, Xx MalesGeneDeletionFemaleFamilyTestisMiceTransmissionHaplotypesAdolescentAdultChildChild, preschoolCytogenetic analysisFemaleGene expression regulationHigh mobility group proteinsSex reversal, gonadalHormonesPedigreeHumansMaleMicrotubule-associated proteinsMutationNeuropeptidesSex-determining region Y proteinReverse transcriptase polymerase chain reactionTestisTranscription factorsExtended pedigree with multiple cases of XX sex reversal in the absence of SRY and of a mutation at the SOX9 locusArticle0002536147000042-s2.0-3424823367324341118391513Developmental biologyGonads; Disorders of Sex Development; Sex DeterminationGene mutationTranscription factor Sox9AdolescentAdultArticleBlood analysisChildChromosome duplicationClinical articleConsanguinityDevelopmental disorderEmbryo developmentFluorescence in situ hybridizationGene locusGene lossHaplotypeSexual developmentHumanSex transformationHuman tissuePedigreeKaryotype 46, XXMaleMutational analysisPhenotypePolymerase chain reactionPriority journalSRY geneTestis developmentTestis diseaseY chromosome