Array-CGH characterization of a de novo t(X;Y)(p22;q11) in a female with short stature and mental retardation

We report the clinical and molecular investigations in a girl with 46,X,-X,+der(X)t(X;Y)(p22;q11) de novo karyotype who presented an intricate phenotype characterized by mental retardation and facial dysmorphisms in combination with short stature. The structure of the derivative X chromosome was studied using BAC array-CGH which disclosed the Xp22 breakpoint between the STS and the VCX3A gene and the presence of the Yq11.1qter chromosome. It is common that females with Xp;Yq translocations present only short stature and are normal in every other aspect. Thus, this would be the first case in which a girl with Xp;Yq translocation presents an unusual phenotype with intermediate male clinical features with Xp;Yq translocations. The risk of developing gonadoblastoma in females with Y chromosome material is also discussed and, to this effect, different explanations related to this apparent variation are also presented.     

Prenatal diagnosis and molecular cytogenetic characterization of de novo partial trisomy 12q (12q24.21 → qter) and partial monosomy 6q (6q27 → qter) associated with coarctation of the aorta,ventriculomegaly and thickened nuchal fold

We present rapid aneuploidy diagnosis of de novo partial trisomy 12q (12q24.21 → qter) and partial monosomy 6q (6q27 → qter) by aCGH using uncultured amniocytes in a fetus with coarctation of the aorta, ventriculomegaly and thickened nuchal fold. We discuss the association of TBX3, TBX5 and MED13L gene duplication with coarctation of the aorta, and the association of RNASET2 gene haploinsufficiency with ventriculomegaly in this case.     

Novel chromosomal translocation (17;22)(q12;q12) in a case of myelodisplastic syndrome characterized with signs of hemolytic anemia at presentation

Myelodysplastic syndromes (MDS) are clonal stem cell diseases that can result in cytopenias, dysplasia in one or more cell lineages, infective hematopoiesis, and increase the risk of progression to acute myeloid leukemia (AML). MDSs are characterized by several recurrent cytogenetic defects, which can affect diagnosis, prognosis, and treatment. Some of that chromosomal alterations are associated with very poor prognosis. Conventional cytogenetics cannot accurately define the rearranged karyotype. Instead, molecular cytogenetics analyses can provide important diagnostic and prognostic information for patients affected by MDS, allowing the characterization of the whole mutational spectrum and, mainly, novel chromosomal lesions.In this paper, we report a MDS case with a novel chromosomal translocation [t(17;22)(q12;q22)], described for the first time here. Following Giemsa-banding karyotyping, fluorescent in situ hybridization analyses, by using chromosome-specific probes, displayed the breakpoint regions at chromosomes 17 and 22, within which intra and inter-chromosomal segmental duplications (SD) are present. Because of the occurrence of SDs in breakpoint region, it was not possible to finely define the genomic regions where breaks fell. Further investigations could be required to better understand the molecular basis of the novel translocation t(17;22)(q12;q12) acting in MDS context and to explain if SDs could contribute to the pathogenesis of MDS.     

Partial monosomy 21 (q11.2→q21.3) combined with 3p25.3→pter monosomy due to an unbalanced translocation in a patient presenting dysmorphic features and developmental delay

We describe a female patient of 1 year and 5 months-old, referred for genetic evaluation due to neuropsychomotor delay, hearing impairment and dysmorphic features. The patient presents a partial chromosome 21 monosomy (q11.2→q21.3) in combination with a chromosome 3p terminal monosomy (p25.3→pter) due to an unbalanced de novo translocation. The translocation was confirmed by fluorescence in situ hybridization (FISH) and the breakpoints were mapped with high resolution array. After the combined analyses with these techniques the final karyotype was defined as 45,XX,der(3)t(3;21)(p25.3;q21.3)dn,-21.ish der(3)t(3;21)(RP11-329A2-,RP11-439F4-,RP11-95E11-,CTB-63H24 +).arr 3p26.3p25.3(35,333-10,888,738)) × 1,21q11.2q21.3(13,354,643-27,357,765) × 1. Analysis of microsatellite DNA markers pointed to a paternal origin for the chromosome rearrangement. This is the first case described with a partial proximal monosomy 21 combined with a 3p terminal monosomy due to a de novo unbalanced translocation.     

An idic(15) associated with POF (premature ovarian failure): molecular cytogenetic definition of a case and review of the literature

We report on a 36-year-old infertile woman, presenting a premature ovarian failure with an otherwise normal female phenotype. Cytogenetic analyses showed the presence of a supernumerary marker chromosome, that was characterized by FISH (fluorescent in situ hybridization) and array CGH (comparative genomic hybridization). This marker chromosome was derived from chromosome 15, and contained only heterochromatic material. The Prader Willi/Angelman region was not present. No duplications of the 15q regions were detected by array CGH. Supernumerary markers of chromosome 15 have been reported in cases of infertility and amenorrhea, that is also described in cases with marker derived by other acrocentric chromosomes. The case here presented constitutes a further example that etiology of POF is not always associated with a defective gene, but in some cases oocytes atresia can be the consequence of the abnormal meiotic pairing of chromosomes.