Immunoglobulin kappa and lambda light chain dual genotype rearrangement in a patient with kappa-secreting B-CLL.

The cytogenetics, immunophenotype and immunoglobulin gene rearrangements were analysed in a consecutive series of 56 patients with lymphoma or lymphatic leukaemia. One patient with B-CLL showed monoclonal rearrangements of the constant mu, kappa and lambda genes. The immunophenotype was kappa-secreting indicating expression of one immunoglobulin light kappa allele.

Clonal chromosomal abnormalities showing multiple-cell-lineage involvement in acute myeloid leukemia.

To determine whether one or more hematopoietic-cell lineages are involved in acute myeloid leukemia (AML), we designed a technique that simultaneously identifies a cell as malignant and determines its lineage. We used numerical clonal chromosomal abnormalities, which are readily detected, to indicate neoplasia, and monoclonal antibodies in an alkaline phosphatase-antialkaline phosphatase detection procedure to identify lineages as granulocytic-monocytic, erythrocytic, or megakaryocytic. Examination of bone marrow from 12 patients with AML showed metaphases of granulocytic-monocytic lineage with abnormal karyotypes in all patients.

Molecular characterization of a Y;15 translocation segregating in a family.

We have used Y-specific and Y-derived DNA probes for in situ hybridization and Southern blotting analysis to characterize a Y;15 translocation showing normal Mendelian inheritance in a family. Cytogenetically there appeared to be an unbalanced translocation of Yqh to 15p; this translocation may be considered as a prototype of those translocations between Yq and the short arm of an acrocentric chromosome which have a population incidence of approximately 1 in 2,000. Our molecular studies showed that, in all probability, the breakpoints were near the border between Yq11.

Y;autosome translocations and mosaicism in the aetiology of 45,X maleness: assignment of fertility factor to distal Yq11.

Three 45,X males have been studied with Y-DNA probes by Southern blotting and in situ hybridization. Southern blotting studies with a panel of mapped Y-DNA probes showed that in all three individuals contiguous portions of the Y chromosome including all of the short arm, the centromere, and part of the euchromatic portion of the long arm were present. The breakpoint was different in each case.

Characterization of a (Y;4) translocation by DNA hybridization.

A phenotypically normal male with azoospermia was found to have a translocation between the short arm of the Y chromosome and the distal long arm of a chromosome 4. By cytogenetic analysis it could not be determined whether the translocation was reciprocal, nor whether it was balanced. In situ DNA hybridization with two pseudoautosomal and one Y-specific probe demonstrated that the breakpoint was on distal Yp and that there was Y chromosome material on 4q.

Monocytic involvement by monosomy 7 preceded acute myelomonocytic leukemia in a patient with myelodysplastic syndrome.

Novel techniques were used to detect which cell lineages were affected by monosomy 7 in a patient who had myelodysplastic syndrome and later developed acute leukemia. The patient had had paroxysmal nocturnal hemoglobinuria for 20 years before developing refractory anemia with excess of blasts. Cytogenetic analysis at the myelodysplastic stage disclosed monosomy 7 in bone marrow mitoses.

Microdeletions in patients with X-linked muscular dystrophy: molecular-clinical correlations.

The DNA from 68 patients with X-linked (Duchenne and Becker) muscular dystrophy belonging to 49 unrelated families was analyzed for microdeletions using 13 closely linked or gene-specific DNA-markers. Fourteen patients from eight families showed a deletion involving a least one of the markers used, giving a deletion frequency of 16%. The proportion of families with deletions was 36% in the Becker and 8% in the Duchenne form of the disease.

[Stickler's syndrome or hereditary progressive arthro-ophthalmopathy].

A case of Stickler's syndrome is reported. This syndrome associates eye defects, craniofacial and musculo-skeletal abnormalities, sensori-neural hearing loss and mitral-valve prolapse. It is an autosomal dominant disorder probably resulting from a connective tissue dysplasia.

[Marden-Walker syndrome. New case and discussion about its role in arthrogryposes].

A new case of Marden-Walker syndrome is reported. The Marden-Walker syndrome is a rare entity associating neonatal arthrogryposis and blepharophimosis with autosomal recessive inheritance. Its place among the various syndromes with neonatal arthrogryposis is discussed.

Linkage studies in a new X-linked myopathy, suggesting exclusion of DMD locus and tentative assignment to distal Xq.

We here report linkage studies in a family suffering from a recently described hereditary muscle disease named X-linked myopathy with excessive autophagy (XMEA). Significant lod scores excluding linkage to the Duchenne-Becker muscular dystrophy locus were found. Several other loci on the short and long arms of the X chromosome produced negative lod scores, whereas probe DX13-7 defining locus DXS15 showed no recombinants and a lod score of z = 0.

Demethylation of two specific DNA sequences in expressed human immunoglobulin light kappa constant genes.

We have analyzed the pattern of methylation of rearranged and germ line C kappa genes in DNA samples from human B-type chronic lymphatic leukemia lymphocytes and normal fibroblasts, and from granulocytes, T-, and non-T-lymphocytes separated from normal blood. C kappa alleles are flanked by one HpaII site on each side. Leukemic B-CLL DNA from five patients showed demethylation of these two sites in the productively rearranged allele and methylation of both sites in the nonexpressed allele whether rearranged or in germ-line configuration.

The sex-determining region of the human Y chromosome encodes a finger protein.

The presence or absence of the Y chromosome determines whether a mammalian embryo develops as a male or female. In humans, genetic deletion analysis of "sex-reversed" individuals has identified a small portion of the Y chromosome necessary and sufficient to induce testicular differentiation of the bipotential gonad. We report the cloning of a 230-kilobase segment of the human Y chromosome that contains some or all of the testis-determining factor gene (TDF), the master sex-determining locus.

[Prevalence of anti-HIV antibodies in immunoglobulins recipients].

Seven hundred and forty subjects who, between 1980 and 1985, had received intravenous or intramuscular injections of immunoglobulins (Ig) prepared by Cohn fractionation of plasma pools from more than 2000 donors were investigated for anti-HIV antibodies. Anti-HIV antibodies were detected in only one subject, a female drug addict and therefore belonging to a group at high risk of AIDS. In contrast with the huge amounts of Ig received by the remaining 739 subjects (976 litres intravenously, 128 litres intramuscularly), this young woman had only received 10 ml of anti-HBs Ig intramuscularly.

The inheritance of fragile sites: apparent absence of fra(2)(q13) in the parents of three unrelated probands.

We describe the inherited folate sensitive fragile site, fra(2)(q13), in three unrelated mentally retarded children, two of them with different forms of epilepsy. Fra(2)(q13) was detected in one healthy sib of one of the probands. Except for one cell in one of the fathers, fra(2)(q13) could not be detected in any of the six parents, who were repeatedly studied using methods known to induce fragile sites of this type.

Monosomy 7 predisposes to diabetes insipidus in leukaemia and myelodysplastic syndrome.

We studied the chromosomes in the bone marrow of 4 patients who had both diabetes insipidus (DI) and acute non-lymphocytic leukaemia. Clinical findings suggested that, in each case, myelodysplastic syndrome had preceded the onset of acute leukaemia. Two other such patients described in the literature had had a banded karyotype study of bone marrow cells.

Linkage, physical mapping, and DNA sequence analysis of pseudoautosomal loci on the human X and Y chromosomes.

The pseudoautosomal region of the human X and Y chromosomes is subject to frequent X-Y recombination during male meiosis. We report the finding of two pseudoautosomal loci, DXYS20 and DXYS28, characterized by highly informative restriction fragment length polymorphisms (RFLPs). The pseudoautosomal character of DXYS20 and DXYS28 was formally demonstrated by comparing their transmission to 45,X and to normal individuals.

Molecular characterization of chromosome 7 long arm deletions in myeloid disorders.

Partial deletion of the long arm of chromosome 7 is a common abnormality in the bone marrow cells of patients with myelodysplastic syndrome (MDS) or acute nonlymphocytic leukemia (ANLL). This study was undertaken to characterize the chromosome breakpoints in molecular terms and to determine if hemizygosity or submicroscopic deletions occur in patients without any cytogenetically detectable abnormality of chromosome 7. We studied restriction fragment length polymorphisms with 10 chromosome 7-specific DNA probes in separated WBC fractions.

Linked polymorphic DNA markers in the prediction of X-linked muscular dystrophy.

Ten polymorphic DNA markers, including gene specific markers of loci DXS164 and DXS206, were tested for allele frequencies, degree of heterozygosity and linkage in 34 Finnish families with X-linked muscular dystrophy. With the exception of the BamHI RFLP of DXS164 subclone pERT87-15, allele frequencies and the degree of heterozygosity failed to show any significant deviation from the data published elsewhere. We document a high degree of linkage disequilibrium between several RFLPs belonging to locus DXS164.

An XXX male resulting from paternal X-Y interchange and maternal X-X nondisjunction.

A 2-year-old boy was found to have a 47,XXX karyotype. Restriction-fragment-length-polymorphism analysis showed that, of his three X chromosomes, one is of paternal and two are of maternal origin. The results of Y-DNA hybridization were reminiscent of those in XX males in two respects.

Prenatal diagnosis of X-linked chronic granulomatous disease using restriction fragment length polymorphism analysis.

Prenatal diagnosis of X-linked chronic granulomatous disease (CGD) was performed with restriction fragment length polymorphism (RFLP) analysis using probes flanking the gene. The male fetus and an affected male displayed the same haplotype for RFLPs belonging to six linked loci extending from DXS164 to DXS7, which encompass the CGD locus, and for which the mother was heterozygous. Diagnosis of an affected fetus was confirmed after termination of the pregnancy by the study of fetal granulocytes using the nitroblue tetrazolium reduction test.

X-linked retinoschisis is closely linked to DXS41 and DXS16 but not DXS85.

A linkage study was carried out in nine families with 24 males affected by X-linked recessive retinoschisis (RS), using three polymorphic DNA probes from the distal segment of Xp. Close linkage of the disease locus with markers DXS41 (probe p99-6) and DXS16 (pXUT23) was found, confirming the location of the RS gene on the distal short arm of the X chromosome. Lod scores for linkage with DXS85 (probe 782) were negative.