A case of (X;15) translocation diagnosed as a paracentric inversion of Xp: diagnostic revision with FISH.

In 1990 we reported the case of a 17 years old girl with growth retardation, overweight and primary amenorrhea, presenting a de novo chromosomal rearrangement cytogenetically characterized as a paracentric inversion of the short arm of X chromosome. The FISH analyses that were recently performed, revealed that in fact our patient presented a case of unbalanced translocation, 46,X, t(X;15)(p11.2; q15).

Parental origin of the deletion 22q11.2 and brain development in velocardiofacial syndrome: a preliminary study.

BACKGROUND: As children with velocardiofacial syndrome (VCFS) develop, they are at increased risk for psychopathology; one third will eventually develop schizophrenia. Because VCFS and the concomitant symptomatology result from a known genetic origin, the biological and behavioral characteristics of the syndrome provide an optimal framework for conceptualizing the associations among genes, brain development, and behavior. The purpose of this study was to investigate the effect of the parental origin of the 22q11.2 microdeletion on the brain development of children and adolescents with VCFS. METHODS: Eighteen persons with VCFS and 18 normal control subjects were matched individually for age and sex. Results of DNA polymorphism analyses determined the parental origin of the deletion. Nine persons with VCFS had a deletion on the maternally derived chromosome 22; 9 persons, on the paternally derived chromosome 22. High-resolution magnetic resonance imaging scans were analyzed to provide quantitative measures of gray and white matter brain tissue. RESULTS: Total brain volume was approximately 11% smaller in the VCFS group than in controls. Comparisons between VCFS subgroups (maternal vs paternal microdeletion 22q11.2) indicated a significant 9% volumetric difference in total volume of cerebral gray matter (volume was greater in patients with paternal microdeletion) but not cerebral white matter. Significant age-related changes in gray matter were detected for subjects whose 22q11.2 deletion was on the maternal chromosome. CONCLUSIONS: Children and adolescents with VCFS experience major alterations in brain volumes. Significant reduction in gray matter development is attributable to presence of 22q11.2 microdeletion on the maternal chromosome.

Familial t(6;21)(p21.1;p13) translocation associated with male-only sterility.

A 38-year-old male with primary infertility was referred for cytogenetic investigation. Karyotype analysis revealed a 46,XY,t(6;21)(p21.1;pl3) translocation. The Ag-nucleolar organizer regions (NORs) banding technique demonstrated that the 21p NORs were retained in the derivative and actively transcribed. Family studies showed that three brothers, two sisters and their mother carried the t(6;21). All carrier males suffered from primary infertility with severe oligoasthenoteratospermia or azoospermia, whereas at least two of the three carrier women were fertile. The region of the translocation breakpoint was narrowed down cytogenetically and by fluorescence in situ hybridisation as 21p13 and 6p21.1. Southern blot analysis showed that the gene ZNF165, which maps to this region and which is specifically expressed in the testis, was not disrupted by the translocation. However, studies performed on testicular biopsy showed spermatocyte meiosis anomalies. We discuss the possible mechanisms by which the translocation might affect meiosis in spermatogenesis and lead to infertility.

A case of 45,X Turner syndrome with spontaneous ovulation proven by ultrasonography.

A well-documented case of non-mosaic Turner syndrome, with spontaneous pubertal development and ovulatory cycles is reported. Mosaicism could be excluded both by karyotyping of 172 metaphases of blood lymphocytes and fibroblasts, and by fluorescence in situ hybridization, using an X-centromeric probe, in 200 blood lymphocyte nuclei. This Turner syndrome patient underwent normal pubertal development, with spontaneous menarche at 14 years, followed by regular monthly periods. Hormonal measurements performed during puberty were consistent with the patient's pubertal development. At the age of 26 years the patient was referred for complete fertility evaluation. Detailed hormonal analyses were performed in a given cycle. They showed midluteal phase estradiol and progesterone values within the range corresponding to normal ovulation and corpus luteum function. In the same cycle, pelvic ultrasonography was also performed at days 13, 15 and 18. It demonstrated a spontaneous ovulation, with follicular rupture that occurred between days 15 and 18. This is the first report of a spontaneous ovulation in Turner syndrome evidenced, not only by hormonal analysis, but also by ultrasonographic demonstration of follicular rupture.

Pure partial trisomy 5q33-->5q35 resulting from the adjacent-1 segregation of a paternal (5;14)(q33;p12) translocation.

A 14-year-old male was referred for evaluation of mental retardation with short stature and dysmorphic features. His karyotype was 46,XY,der(14)t(5;14)(q33;p12)pat, resulting in a pure partial 5q33-q35 trisomy due to the adjacent-1 segregation of a paternal balanced translocation. Paternal blood karyotype revealed a balanced translocation t(5;14)(q33;p12) retaining Ag-Nors. To date, only two cases of pure partial 5q trisomies spanning this region have been reported. Analysis of these cases and the one we report does not allow the delineation of a specific phenotype.

A proven case of materno-foetal transfusion determined by cytogenetic and DNA analysis.

We report a case of materno-foetal transfusion in a phenotypically normal male foetus after death in utero at the 35th week of gestation. We have used cytogenetic and polymerase chain reaction (PCR) microsatellite analysis to determine the presence of maternal cells in foetal blood collected by intracardiac puncture. In the intracardiac blood sample, maternal cells were estimated to comprise between 5 and 10% of nucleated foetal blood cells. When there is a suspicion of foetal genetic pathology, it is necessary to be aware that the foetal blood karyotype may be misrepresentative, as the analysed blood cells can indeed be of maternal origin.

Amplification of a pseudogene cassette underlies euchromatic variation of 16p at the cytogenetic level.

Euchromatic imbalances at the cytogenetic level are usually associated with phenotypic consequences. Among the exceptions are euchromatic variants of chromosomes 8, 9, 15 and 16, which have each been reported in multiple unrelated families. In this paper, we present a new family and an unrelated individual who have euchromatic variants of 16p. Enhanced hybridisation to the extra material was found by using fluorescence in situ hybridisation with cosmids for both the 16p11.2-specific non-functional immunoglobin heavy chain segments and the pseudogenetic 16p11.2 creatine transporter region. Computerised measurement of the fluorescent signals was consistent with amplification of a pseudogene cassette comprising both these paralogous domains, which were originally transposed from 14q32.3 and Xq28, respectively. Amplification of pseudogenetic sequences is consistent with the normal phenotype in 36/46 carriers from the 18 families reported to date. Inconsistent phenotypic anomalies in the remaining 10 carriers probably reflect bias of ascertainment. These results are analogous to the amplification of the 15q11.2-specific pseudogene cassette in euchromatic variants of chromosome 15. They also suggest that the majority of established euchromatic variants are associated with variation in the copy number of sequences that have been dispersed between pericentromeric and telomeric loci over recent evolutionary time. We propose that constitutional cytogenetic amplification of this kind is part of a more widespread continuum of genomic flux affecting regions in which heterochromatin and euchromatin interpose. Euchromatic sequences that vary in a heterochromatic manner might usefully be termed "hemichromatic".