Paul Petit

Cytogenetic survey in couples with recurrent fetal wastage.

SummaryCytogenetic studies have been performed in 1068 couples with antecedent fetal wastage, i.e., at least two spontaneous first trimester abortions or one spontaneous first trimester abortion and one late fetal death, particularly with multiple congenital malformations.Three major types: 33 reciprocal translocations (3.09%), 20 Robertsonian translocations (1.87%) and six other chromosomal abnormalities (0.56%) were found, bringing the total number of chromosomal abnormalities to 59 (5.5%) in 1068 couples under investigation.In contrast to couples with reciprocal translocations, a high excess of female over male carriers was found in the group of Robertsonian translocations.In the evaluation of chromosomal polymorphisms, only variants with particularly large paracentromeric constitutive heterochromatin blocks were taken into account, and their low frequency in the present study is therefore not comparable with that in a general population.The impact of further extensive familial investigation on genetic counseling and the follow-up of prenatal diagnosis are discussed.

Interstitial telomeric sequences at the junction site of a jumping translocation.

Abstract The mechanism(s) for the origin of jumping translocations (JTs) are unknown. To assess the possible involvement of telomeric sequences in the jumping process, metaphases of a patient with hydrops fetalis having a JT were analyzed for the presence of interstitial telomeres. Telomere DNA sequences were detected at the junction sites of the donor and the recipient chromosomes. Interstitial telomeric sequences have so far only been detected in JTs involving chromosome 15q in patients with Prader-Willi syndrome. Our finding of interstitial telomeric sequences in a JT with a chromosome different from chromosome arm 15q in a patient without Prader-Willi syndrome implies that telomere sequences may be common to all telomeric JTs. The possible role of telomeric sequences as a cause of the observed chromosomal mosaicism is discussed.

Fertility in patients with X chromosome deletions

Three fertile, non‐mosaic patients with partial monosomy of an X‐chromosome (two with Xp deletion with breakpoints at Xpl 106 and Xp2101, respectively, and one with a del(Xq25)) were found among 12 females with Xp deletion and three with Xq deletion investigated in this laboratory after the advent of banding techniques. Four phenotypically normal children resulted from a total of seven pregnancies in these women. Three of the children were chromosomally normal and one girl presented the same del(Xp) as her mother. The possibility of having genotypically and phenotypically normal offspring should be taken into account in the management and genetic counseling of children and females with X‐chromosome deletions.

Trisomy 15 rescue with jumping translocation of distal 15q in Prader-Willi syndrome.

We report a patient with Prader-Willi syndrome (PWS) and mosaicism for a de novo jumping translocation of distal chromosome 15q, resulting in partial trisomy for 15q24-qter. A maternal uniparental heterodisomy for chromosome 15 was present in all cells, defining the molecular basis for the PWS in this patient. The translocated distal 15q fragment was of paternal origin and was present as a jumping translocation, involving three different translocation partners, chromosomes 14q, 4q, and 16p. The recipient chromosomes appeared cytogenetically intact and interstitial telomere DNA sequences were present at the breakpoint junctions. This strongly suggests that the initial event leading to the translocation of distal 15q was a non-reciprocal translocation, with fusion between the 15q24 break-point and the telomeres of the recipient chromosomes. These observations are best explained by a partial zygotic trisomy rescue and comprise a previously undescribed mechanism leading to partial trisomy.

Y to X translocation in man

SummaryFive new cases are added to the single published instance of Yq to Xp translocation (Xt) in man. It is shown that the anomaly can occur as a mutational event during meiosis, and can be inherited from a parent, but also that it can arise in a 47,XXY embryo. In individuals with 46,XXt karyotype the gonadal development, sexual differentiation, gonadal function and fertility are within the range of normal females. They do not present overt or discrete sings of virilisation. However, somatic stigmata, and more specifically short stature, are present in all patients. There is no uniform pattern of Xt inactivation which varies from random to apparently preferential inactivation. This phenomenon may be important for the better understanding of X-inactivation which for the Xt the authors believe is random but followed by differential proliferation of the resulting two types of cells.

De novo 7q36 deletion: breakpoint analysis and types of holoprosencephaly.

We report on a de novo 7q36 deletion in a 3-month-old girl with manifestations of the 7q terminal deletion syndrome. Only minimal findings of holoprosencephaly (HPE) were present since only a partial corpus callosum hypoplasia was seen on a magnetic resonance imaging scan of the brain. Extensive fluorescence in situ hybridization analysis showed that the HPE3 critical gene region, inclusive Sonic hedgehog (SHH), En2 (HOX1), and HTR5A, was deleted. A review of 33 other patients with a de novo terminal 7q deletion and the different types of HPE manifestations within these patients will be presented.

Mosaic Tetrasomy 21 in Severe Mental Handicap

A 5-year-old boy with severe mental handicap, dysmorphic stigmata and a tetrasomy 21 in fibroblasts is reported. Blood lymphocytes of the patient have a normal karyotype. The origin of this tetrasomy 21 mosaicism is discussed.

The various phenotypes in Xp deletion. Observations in eleven patients

SummaryEleven Xp-deletion patients with various phenotypes ranging from normal to the Turner syndrome are reported. To explain the phenotypy-karyotype correlation the hypothesis is brought forward that (an) autosomal gene(s) may play a role in the pathogenesis of the Turner syndrome.

X‐chromosome polysomy in the female: personal experience and review of the literature

The mental, physical and sexual development of 15 triple‐, four tetra‐, and one penta‐X patients is described and the most important data on this subject are reviewed.

Simultaneous occurrence of 5q− and 21q− in refractory anemia with thrombocytosis

Abstract A 40-yr-old female with refractory anemia and thrombocytosis was shown to possess 5q− and 21q− chromosomal anomalies in the hematopoietic cells. The former anomaly was demonstrated to be a del(5)(q14q32) and the latter to be due to a t(11;21)(q25;q21). A similar translocation was shown to exist in the cells of another patient with essential thrombocytosis. Thus, we tentatively identify the 21q− as being due to a t(11;21).