Novel unbalanced X-autosome translocation in a woman affected with Primary Ovarian Failure

DEL REY GRACIELA; ROBERTO COCO; ANDREA ARCARI

CYTOGENETIC AND GENOME RESEARCH

KARGER

Lugar: Basel; Año: 2016 vol. 148

1424-8581

Novel unbalanced X-autosometranslocation in a woman affected with Primary Ovarian Failure. Graciela del Reyª, Andrea Arcariª and Roberto Cocoº.ªCentro deInvestigaciones Endocrinológicas ?Dr César Bergadá? (CEDIE). CONICET. FEI.Hospital de Niños ?Ricardo Gutiérrez?, and ºFecunditas, Buenos Aires,Argentina. Email: gracieladelrey@cedie.org.ar  The cause of premature ovarian failure (POF) remains unknown in several cases.Xq chromosomal rearrangements such as deletions or balanced X-autosometranslocations (X;A) show two critical specific regions: POF1 (Xq26-qter) andPOF2  (Xq13.3-q21.1). Microdeletions atthese breakpoints  have been characterizedin only half of the cases. In the others X-A two mechanisms have been proposed:one is ascribed to the XIST-mediated inactivation to the autosomal translocatedregion, and the other a position effect variegation due to epigeneticmodifications in genes located near the constitutive heterochromatin of thepericentromeric regions.Our purpose is to communicate an apparent balanced translocation betweenchromosome 1 and the X, but using STRs linked to Xq28 loci and the triplet expansion of Fra-X showed three alleles,one from the father and two from the mother.  The patient was referred forshort stature at age 3.1 yrs. Height 86cm(-2SDS); Weight 11Kg(below Pc3).Infancy showed delay in growth development and no progressive motor neuropathy.She started breast development at 11 yrs old. At age 14 she presented hypergonadotropicPOF. Cytogenetic studies were performed with CTG, CBG and RHG bandingtechniques. The Fra-X (Xq27.3) was studied by QF-PCR, and in addition severalSTRs: DXS8091, DXS8377, DXS1068, DXS8069 linked to Xq28.  De novo karyotype of theproband was: 46,X,der(X)t(X;1)(qter;q12) meaning that a whole chromosome X was translocatedon the heterochromatin 1q12. The STRs linked to Xq27.3 and Xq28 revealed threealleles, two maternal and one paternal origin showing a de novo microduplicationin the distal portion of Xq. Late-replication studies revealed the existence ofskewed X inactivation in derivative X chromosome. This case is a novel X-A translocation found in awoman with POF. The results of the cytogenetic molecular studies support the proposalof the position effect of the translocated-X on flanking genes resulting insilencing of gene expression.