Evidence for an ancestral alphoid domain on the long arm of human chromosome 2.

In situ hybridization, under low stringency conditions with two alphoid DNA probes (pY alpha 1 and p82H) labeled with digoxigenin-dUTP, decorated all the centromeres of the human karyotype. However, signals were also detected on the long arm of chromosome 2 at approximately q21.3-q22.1. Since it is supposed that human chromosome 2 originated by the telomeric fusion of two ancestral primate chromosomes, these findings indicate that not only the telomeric sequences, but also the ancestral centromere (or at least its alphoid sequences), have been conserved.

Deletion of the distal short arm of the X chromosome (Xp) in a patient with short stature, chondrodysplasia punctata, and X-linked ichthyosis due to steroid sulfatase deficiency.

We observed a boy with short stature, chondrodysplasia punctata, ichthyosis, and a terminal deletion of Xp. Steroid sulfatase deficiency was demonstrated in the patient's fibroblasts. Molecular analysis showed a deletion of the entire steroid sulfatase gene. This case represents another example of a contiguous gene syndrome in which the co-deletion of adjacent genes on a chromosome is responsible for a complex phenotype.

Mapping the gene encoding the human erythroid transcriptional factor NFE1-GF1 to Xp11.23.

The X-linked NFE1 gene encodes an erythroid factor involved in globin gene transcription. Using a human cDNA clone encoding this factor, we show, by in situ hybridization and by analysis of human-rodent hybrid cell lines, that this gene is located in Xp11.23. In the absence of polymorphisms in the NFE1 gene, these results allow the study of the possible relationships between NFE1 mutations and X-linked hereditary persistence of fetal hemoglobin by linkage analysis with RFLP markers of the region. A female patient, hemizygous for the NFE1 locus, shows essentially normal hematological parameters.

Deletion of specific sequences or modification of centromeric chromatin are responsible for Y chromosome centromere inactivation.

Stable dicentric chromosomes behave as monocentrics because one of the centromeres is inactive. The cause of centromere inactivation is unknown; changes in centromere chromatin conformation and loss of centromeric DNA elements have been proposed as possible mechanisms. We studied the phenomenon of inactivation in two Y centromeres, having as a control genetically identical active Y centromeres. The two cases have the following karyotypes: 45, X/46,X,i(Y)(q12) and 46,XY/47,XY,+t(X;Y) (p22.3;p11.3). The analysis of the behavior of the active and inactive Y chromosome centromeres after Da-Dapi staining, CREST immunofluorescence, and in situ hybridization with centromeric probes leads us to conclude that, in the case of the isochromosome, a true deletion of centromeric chromatin is responsible for its stability, whereas in the second case, stability for its stability, whereas in the second case, stability of the dicentric (X;Y) is the result of centromere chromatin modification.

Cytogenetic and molecular analysis of an unbalanced translocation (X;7) (q28;p15) in a dysmorphic girl.

A severely retarded and dysmorphic girl, carrying an unbalanced X/7 translocation with breakpoints at Xq28 and 7p14, was analyzed by cytogenetic, biochemical and molecular techniques. The X/7 translocated chromosome was found to replicate consistently late in the 105 metaphases analyzed. In 83 of these cells, late replication was limited to the X portion of the abnormal chromosome, whereas in 22 cells incomplete spreading into the autosomal fragment was observed. Southern blot and in situ hybridization experiments with probe G80 (locus D7S373) (previously localized to 7p13-15) and G98 (localized to 7p14-15) assigns the former to 7p15 and the latter to 7p14, thus suggesting the order 7ter-G80-G98-cen. The activity of the enzyme phosphoserine phosphatase localized to 7pter-p14 was increased. Southern blotting experiments with 19 probes spanning the entire X chromosome demonstrated that the translocated chromosome had lost a portion of Xq28 (locus DXS51) but still retained part of Xq27 (F9 locus). The results confirm that the proband is trisomic for the region 7p15-pter and monosomic for the region Xq28-qter. Comparing her phenotype with those of other cases of partial trisomy or monosomy 7p, we confirm that band 7q21 is probably involved in skull development.

Alternate centromere inactivation in a pseudodicentric (15;20)(pter;pter) associated with a progressive neurological disorder.

A 13 year old male with a severe progressive neurological disorder was found to have a pseudodicentric chromosome resulting from a telomeric fusion 15p;20p. In lymphocytes, the centromeric constriction of the abnormal chromosome was always that of the chromosome 20, while in fibroblasts both centromeres were alternately constricted. Cd staining was positive only at the active centromere, but a weak anticentromere immunofluorescence was present at the inactive one. We suggest that centromere inactivation results from a modified conformation of the functional DNA sequences preventing normal binding to centromere specific proteins. We also postulate that the patient's disorder, reminiscent of a spongy glioneuronal dystrophy as seen in Alper's and Creutzfeldt-Jakob diseases, may be secondary to the presence of the pathogenic isoform of the prion protein encoded by a gene mapped to 20p12----pter.

[An update on gonadal differentiation]. / Attualità in tema di differenziazione gonadica.

The Y chromosome plays a determinant rôle in human maleness. Studies on individuals with sex chromosome abnormalities indicate that a testis determining factor (TDF) is located on the short arm of the Y chromosome. A candidate gene, recently cloned, encodes a protein with multiple "finger" domains of a type known to bind DNA and control transcription. The puzzling finding that on the short arm of the X chromosome is located and homolog gene escaping X inactivation raises problems on the functional relationship of the two genes. The whole of the molecular studies using Y-specific probes have shown that XX males result from the transposition of TDF from the short arm of the Y to that of X chromosome; at least some XY females result from the same transposition, that leaves the Y chromosome without its distal short arm, TDF included. In XO males, the TDF is translocated to an autosome; according to the deletion of the latter, different malformation patterns may be present in these patients. If the presence or the absence of a critical segment of the Y chromosome do explain many instances of sex several, an outstanding problem is still represented by XX hermaphrodites since no Y-specific sequences have been found in their genome. Thus although the Y-chromosome testis- determining factor seems to play a pivotal rôle in sex determination, testicular tissue can be formed in the absence of it.

Regional assignment of the loci for adenylate kinase to 9q32 and for alpha 1-acid glycoprotein to 9q31-q32. A locus for Goltz syndrome in region 9q32-qter?

Normal levels of adenylate kinase (AK-1) and of alpha 1-acid glycoprotein (ORM1) were found in a girl with a deletion 9q32-qter secondary to a maternal translocation (4q35; 9q32), thus excluding these loci from the deleted region. These results, and comparison with other informative data, map the locus for AK-1 to 9q32 and that for ORM1 to region 9q31-q32. The girl has several signs of the Goltz syndrome (Focal dermal hypoplasia), which is listed in the McKusick catalog (no. 30560) as an X-linked dominant condition. Our finding indicates that the locus for Golz syndrome is autosomal and in region 9q32-qter or that there are two such conditions, one autosomal and one X-linked.