J. M. J. C. Scheres

The most common fragile site in man is 3p14

SummaryIn man a common fragile site is known to occur at 3p14. We studied the expression of this fragility in a group of 70 normal healthy subjects. Chromosome breaks, chromatid breaks and gaps at 3p14 could be observed in every examined individual, and in a total of 7000 metaphases they were seen in a mean of 4% of cells. Fluorescence studies in ten persons with chromosome No. 3 polymorphism showed that in all cases both Nos. 3 were about equally liable to breakage. A considerable variation in the fra 3p14 expression was found between individuals as well as in repeated cultures from the same person. Neither sex nor age influences could be detected. Cultures with a high percentage of lesions at 3p14 tended to have also a high number of lesions at other sites. Methotrexate and fluorodeoxyuridine markedly enhanced the expression of fra 3p14 and other fragilities. It is concluded that the chromosomal region at 3p14 represents mans most common fragile site, the expression of which seems to be influenced by environmental and heritable factors.

Identification of two Robertsonian translocations with a Giemsa banding technique

SummaryUsing a trypsin banding technique a D/D and a G/G translocation were identified as D-13/14 and G-21/22.ZusammenfassungMit Hilfe einer Trypsin-Bandierungstechnik wurde eine D/D-und eine G/G-Translokation als D-13/14 und G-21/22 identifiziert.

Evolutionary conservation of fragile sites induced by 5-azacytidine and 5-azadeoxycytidine in man, gorilla, and chimpanzee

SummaryLymphocyte cultures from man, gorilla, and chimpanzee were treated with 5-azacytidine and 5-azadeoxycytidine. These cytidine analogues induce common fragile sites in the chromosome bands 1q42 and 19q13 of man. A rare fragile site is induced by 5-azadeoxycytidine in the band 1q24. The optimum conditions required for inducing these new fragile sites were determined by a series of experiments. The common fragile site in human chromosome 1q42 also exists in the gorilla and chimpanzee in the homologous band 1q32. The fragile site in human chromosome 19q13 was demonstrated in the gorilla in the homologous chromosome band 20q13. These are the first examples found of evolutionary highly conserved fragile sites in homologous chromosome bands in related primate species. The interaction between 5-azacytidine, 5-azadeoxycytidine, and chromosomal DNA; the evolutionary conservation of genes located within or closely adjacent to the fragile sites in the chromosome 1 of Hominoidea; and the phylogenetic origin of the two new common fragile sites are discussed.

A presumptive tetrasomy for the short arm of chromosome 9

SummaryFor the identification of an extra chromosome in a female child a number of recently developed staining techniques were used.The extra element found in 86% of the patients peripheral lymphocytes resembles an isochromosome for the short arm of chromosome No. 9, in which case a tetrasomy for this arm would exist. The clinical findings in our patient were compared with those in patients reported to have extra chromosome 9 material.

Karyotype Instability With Multiple 7/14 and 7/7 Rearrangements

SummaryChromosomes were studied in a mentally retarded boy with microcephaly, growth retardation, facial erythema, café-au-lait spots, and IgA deficiency. In the lymphocytes there was a remarkable tendency to exchange parts of the chromosomes Nos. 7 and 14, the translocations almost exclusively taking place in bands 7p13, 7q32 and 14q11. Seven different types of rearrangements between Nos. 7 and 14, and some other chromosomal aberrations were found. No abnormalities could be detected in the bone marrow. The patient somewhat resembles those affected with ataxia-telangiectasia or with Blooms syndrome, but on clinical and cytogenetic grounds these disorders could be excluded.7/14 Translocations similar to those found in our patients lymphocytes have been reported to occur very rarely in the lymphocyte cultures of individuals with apparently normal chromosome constitution. A relationship between these phenomena may exist.

Complex glycerol kinase deficiency syndrome explained as X-chromosomal deletion.

Sirs, Recently, several of us described a family in which three boys suffered from an apparently X-linked syndrome consisting of progressive muscular dystrophy similar to the Duchenne type, adrenal hypoplasia (AH) and glycerol kinase (GK) deficiency (Reiner et al. 1983). Because DMD, AH and GK deficiency are separate X-linked entities, we considered that this disorder might be caused by a small deletion including the three respective gene loci. In the meantime, several cases with GK deficiency have been described that are clinically very similar to our cases (v. Petrykowski et al. 1982, Bartley et al. 1982, Ginns et al. 1984). This has opened up the possibility that all symptoms in these cases are pleiotropic effects of, and thus causally related to, GK deficiency. According to this hypothesis, the marked clinical heterogeneity of the GK syndrome (Ginns et al. 1984) might be attributable to allelic variation. Alternatively, heterogeneity could be explained by some cases being caused by point mutations and others by deletions, or by deletions of varying size. In an attempt to decide between these interpretations we have re-examined two affected boys of our family by probing their DNA with cloned sequences from the short arm of the X-chromosome. One of these, the recently isolated 754 probe from the middle of Xp (M. H. Hofker* el al. 1985 [in press]) consistently failed to yield hybridization signals in PstI, BglII

Trisomy for the short arm of chromosome No. 10

The clinical and cytogenetic data are presented of a child with multiple congenital malformations, including cystic kidneys. A trisomy for at least the larger part of the short arm of chromosome No. 10 in association with a translocation between chromosomes Nos. 10 and 14 was found in peripheral blood lymphocytes and skin fibroblasts. Both the mother and a younger sib were balanced carriers of the translocation.

Chromosome 7 in ataxia-telangiectasia

ATAXIA-TELANGIECTASIA, or the Louis-Bar syndrome, is a recessive autosomal disorder clinically characterized by progressive cerebel lar ataxia, oculocutaneous telangiectasia, immunodef ic iency, and a predisposi t ion to the deve lopment o f neoplasia. Most often pat ients die f rom pu lmona ry insufficiency or cancer in the first two decades of life. A T is one of the classical ch romosome breakage syndromes; the cells of the pat ients usually display an increased f requency of spontaneous chromosome breaks and rear rangements . C h r o m o s o m e 14 abnor malities are especially f requent and very often there is a t andem 14q/14q translocation, a so-called Dq + marker c h r o m o s o m e ; , Recent ly we have detected ano the r chromosomal abnormal i ty which might be especially associated with AT: in three subsequent ly studied patients we did not find D q + markers but typical ch romosome 7 abnormal i t ies .

15/17 translocation in acute promyelocytic leukaemia.

SummaryA translocation between a chromosome 15 and a chromosome 17 was found in the bone marrow of a 14-year-old boy who had clinical and laboratory symptoms of acute promyelocytic leukemia (APL). As far as we know, this is the sixth case of APL with 15/17 translocation to be reported in the literature. This observation gives further support to the hypothesis that there is an association between this chromosomal rearrangement and APL.

Reverse differential staining of sister chromatids.

Abstract A technique for the differential staining of sister chromatids with basic fuchsin is described. The resulting staining pattern is the reverse of that obtained with a similar technique using Giemsa dye.