Chromosome 9 of Ellobius lutescens is the X chromosome.

Ellobius lutescens carries an apparently identical karyotype (2n = 17) in both sexes. On the basis of indirect evidence the unpaired chromosome 9 has been considered to represent the X chromosome of this species. We have obtained data to substantiate this view by four different techniques.

A comparative mapping study of fragile sites in the human and murine genomes.

Fragile sites on murine chromosomes were induced by the antimetabolites methotrexate (MTX), fluorodeoxyuridine (FdU), and aphidicolin (APD). To facilitate chromosome identification the analysis was performed on chromosomes of a CD/CD mouse that possesses nine pairs of Robertsonian translocation chromosomes of known arm composition. The pattern of induced fragile sites was rather similar for the different antimetabolites used.

Tetrasomy for the short arm of chromosome 12 with accessory isochromosome (+i(12p)) and a marked LDH-B gene dosage effect.

A fetus with tetrasomy for the short arm of chromosome 12 due to a de novo accessory isochromosome i(12p) is described. Involvement of the 12p in this chromosome aberration was suggested by banding analysis and substantiated by detection of a marked increase of LDH-B in the fetal fibroblasts. The syndrome shown by this fetus includes many of the minor anomalies described for live-born patients with partial trisomy 12p, and in addition malformations including brachymelia, anal atresia and double kidneys.

[Long-term study of chronic glaucoma treated with beta blockers (timolol)].

In the study presented here the authors documented 50 patients with chronic glaucoma, aged between 42 and 86, who were followed up on an outpatient basis for a minimum of 3 and a maximum of 6 years. The results can be summarized as follows: 1) treatment with timolol resulted in an average lowering of intraocular pressure by 6 mm Hg, without any fall-off in effect over several years; 2) there was no deterioration in visual fields or visual acuity during treatment with timolol, and in some cases there was an improvement; 3) in the cases of angle-closure glaucoma the therapy was combined with pilocarpine; this resulted in a greater lowering of pressure than that achieved by treatment with timolol alone in cases of open-angle glaucoma.

Dermatoglyphic peculiarities in families with X-linked mental retardation and fragile site Xq27: a collaborative study.

The dermatoglyphic patterns of fingertips, palms and soles of 75 male patients with X-linked mental retardation and fra-Xq27 and of 28 obligate female heterozygotes were analyzed and compared with the data from 200 male and 200 female control individuals. The results show that there is a strong association between the fra-X-syndrome and dermatoglyphic peculiarities observed in male patients and also in female heterozygotes. The characteristic dermatoglyphic features of the fra-X-syndrome are: increased frequencies of radial loops, whorls and arches on the fingertips, a pronounced transversal course of palmar ridges, lower a-b RC, absence of c-triradii on the palms, abnormal palmar and plantar creases, dysplasia of the papillary ridges and low frequencies of true patterns on the soles.

Familial pericentric inversion of chromosome 12.

A pericentric inversion in one of the chromosomes 12, found in two families living in the same region, is described. This inversion was detected during routine chromosomal analysis in two separate laboratories. The breakpoints were at 12p112 and 12q13.

Mental impairment in Martin-Bell syndrome is probably determined by interaction of several genes: simple explanation of phenotypic differences between unaffected and affected males with the same X chromosome.

A family with Martin-Bell syndrome (MBS) is described with transmission of this X-linked trait by a normal male who manifested the fragile site at Xq27. This family shows features apparently typical for all families with a normal male transmitter. The daughters of this male are mentally normal and their fragile site is difficult or impossible to detect but detection of the heterozygous genotype is much easier among the granddaughters.

Fragile X: carrier detection in pregnancy.

The expression of the fragile X in 9 pregnant women (4 obligate carriers and 5 carriers at risk) was not significantly different from the expression observed either before or after pregnancy in the same individuals. Hence, carrier diagnosis during pregnancy seems to be as reliable as in non-pregnant women.

The significance of pericentric inversions of chromosome 2.

Thirteen new cases of a pericentric inversion 2 collected from different laboratories are reported. In addition 41 cases of a pericentric inversion 2 were reviewed from the literature. The pooled data were analysed using Weinberg's proband method to evaluate the risk of a carrier for either children with congenital anomalies or reproductive wastage.

Prenatal diagnosis of a true mosaic trisomy 20 substantiated by demonstration of a gene dosage effect for adenosine deaminase (ADA).

Fibroblasts from a fetus with the prenatal diagnosis of mosaic trisomy 20 were cloned by dilution plating. Adenosine deaminase (ADA), a biochemical marker for chromosome 20, was assayed in trisomic clones and normal clones as control. The cytogenetic diagnosis was substantiated by demonstration of a triplex gene dosage effect for ADA in the trisomic cells.

On the significance of true trisomy 20 mosaicism in amniotic fluid culture.

Nine new cases of prenatally detected true mosaic trisomy 20 (T20) are reported. In three instances the fetuses were aborted. One fetus showed multiple malformations associated with a high percentage of T20 cells among amniotic fluid (AF) cells and fibroblasts of different fetal tissues.

Manifestation of the fragile site Xq27 in fibroblasts. IV. Clones from a heterozygous female do not manifest this site homogeneously on either the early or late replicating X chromosome.

Fibroblasts from a heterozygous carrier for the Martin-Bell syndrome, who manifests the fragile site Xq27, were cloned to separate the population carrying the primary defect on the active X chromosome from the population with this defect on the inactive X. Clones with this defect on the active X manifest the fra(X)(q27) whereas clones from the other population are fra(X)-negative (Steinbach et al. 1983b).

Folic acid sensitive fragile sites are not limited to the human karyotype. Demonstration of nonrandom gaps and breaks in the Persian vole Ellobius lutescens Th. inducible by methotrexate, fluorodeoxyuridine, and aphidicolin.

At least four folic acid sensitive fragile sites have been detected in the karyotype of the Persian vole Ellobius lutescens Th. (Rodentia, Microtinae). Two such "hot spots" are located on chromosome 1 flanking the pericentric segment which is inverted in many individuals.

Evidence against close linkage of the loci for fraXq of Martin-Bell syndrome and for factor IX.

Linkage between the loci for fraXq of Martin-Bell syndrome and factor IX was studied in nine families exhibiting this syndrome by means of a restriction fragment length polymorphism at the factor IX locus. Computer analysis of the data indicates there to be no evidence for close linkage between the syndrome and the factor IX locus.

Multiple congenital anomalies/mental retardation (MCA/MR) syndrome due to interstitial deletion 1q.

A severely retarded male infant was found to have a previously undescribed multiple congenital anomalies/mental retardation (MCA/MR) syndrome including microdolichocephaly, prominence of metopic suture, coarse scalp hair, epicanthus, anteverted nostrils, micrognathia, posteriorly angulated malformed auricles, preaxial hexadactyly, clinodactyly, camptodactyly, hypospadias, cryptorchidism, inguinal hernias, agenesis of left kidney, and pyloric stenosis. This syndrome was due to an interstitial del(1)(q25.2q31.

A patient, mosaic for Rh and Fy antigens lacking other signs of chimerism or chromosomal disorder.

A patient who shows two populations of RBC, differing in their Rh and Fy antigens, was investigated but no other sign of chimerism or mosaicism in a variety of other antigenic systems, including serum and enzyme polymorphisms and HLA antigens, was observed. His karyotype, as investigated on lymphocyte and fibroblast cultures, was normal. Possible explanations of the observed phenomenon are discussed.

Familial paracentric inversion inv(3)(q21q25.1). Case report and review of the literature.

A second case of a paracentric inversion 3q is described. This anomaly was detected during prenatal analysis and found to be inherited from the father.

Nonrandom distribution of methotrexate-induced aberrations on human chromosomes. Detection of further folic acid sensitive fragile sites.

Eleven folic acid sensitive fragile sites (3p14, 7p13, 7q31.1, 7q32, 9q32, 11p13, 14q23, 15q22, 16q23, Xp22.2, Xq22) were detected in one individual, eight of them previously unknown.

Expression of the fragile site Xq27 in fibroblasts. II. Evidence for negative and positive clones from heterozygous females and possible relationship between frequency and phenotype.

An investigation of fibroblast clones from two females heterozygous for the Martin-Bell syndrome showed that the fibroblasts of these individuals consist of two sub-populations, one with cells expressing the fra(X)(q27) and another with cells in which this fragile site cannot be induced. This is to be expected and is in contrast to the fibroblast clones of hemizygous patients investigated earlier. The expression of fra(X)(q27) in females evidently depends on the presence of an X-linked defect with the normal allele inactivated on the other X chromosome.

Expression of the fragile site Xq27 in fibroblasts. I. Detection of fra(X)(q27) in fibroblast clones from males with X-linked mental retardation.

Twelve fibroblast clones from two males with X-linked mental retardation expressed the fragile site Xq27 in 3%-38% of metaphases analyzed. The number of in vitro doublings during the cloning procedure had no evident influence on the induction of fragile X expression. The variability of fragile X expression seems to depend on cell properties acquired during culture rather than on properties originally inherent in the cells.