Distinct spectrum of CFTR gene mutations in congenital absence of vas deferens.

Congenital absence of the vas deferens (CAVD) is a frequent cause for obstructive azoospermia and accounts for 1%-2% of male infertility. A high incidence of mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene has recently been reported in males with CAVD. We have investigated a cohort of 106 German patients with congenital bilateral or unilateral absence of the vas deferens for mutations in the coding region, flanking intron regions and promotor sequences of the CFTR gene.

Analysis of the CAG repeats in the SCA1 and B37 genes in schizophrenic and bipolar I disorder patients: tentative association between B37 and schizophrenia.

We have genotyped unrelated French Alsatian schizophrenic and bipolar I disorder (BPD) patients and matched controls for the polymorphic CAG repeats within the genes for spinocerebellar ataxia type 1 (SCA1) and dentatorubral-pallidoluysian atrophy (B37), in order to test their possible involvement in these disorders. No alleles with abnormally expanded repeats were found in either gene in patients and controls. Differences in allele and genotype frequencies for the SCA1 CAG repeat between patients and controls were not significant, thus providing no support for its role as a possible positional candidate gene for schizophrenia and BPD in our patients.

Dopamine D3 receptor gene: organization, transcript variants, and polymorphism associated with schizophrenia.

DNA fragments from a genomic library were used to establish the partial structure of the human dopamine D3 receptor gene (DRD3). Its coding sequence contains 6 exons and stretches over 40,000 base pairs. The complete DRD3 transcript and three shorter variants, in which the second and/or third exon are deleted, were detected in similar proportions in brains from four controls and three psychiatric patients.

BalI and MspI polymorphisms of the dopamine D3 receptor gene in African Blacks and Caucasians.

An exonic BalI polymorphism and an intronic MspI polymorphism of the dopamine D3 gene were genotyped in 101 Caucasians from the Alsace and in 56 people from the Congo. This is the first study of the BalI polymorphism in sub-Saharan Africa and the first population study of the MspI site. BalI allele 1 was rare in the Congo (0.

Inverted and satellited Y chromosome in the orangutan (Pongo pygmaeus).

An inverted and satellited Y chromosome of almost acrocentric appearance was detected in seven of 14 male orangutans. In the remaining seven animals a submetacentric Y chromosome without NORs occurred. The high frequency with which the satellited Y chromosomes were associated with acrocentric autosomes and the positive AgNO3-staining of their satellite stalks clearly indicate the active state of the NOR on the Y chromosomes.

Association between schizophrenia and homozygosity at the dopamine D3 receptor gene.

Disturbances in dopamine neurotransmission have been postulated to underlie schizophrenia. We report data from two independent studies of a BalI polymorphism in the dopamine D3 receptor gene in patients with schizophrenia. In both studies, more patients than controls were homozygous (p = 0.

Clinical reinvestigation and linkage analysis in the family with Episkopi blindness (Norrie disease).

We present the results of a clinical and genetic reinvestigation of the Cypriot family affected by an X chromosomally inherited eye disease originally published by Taylor et al, who coined the term Episkopi blindness. The pedigree was extended to 160 members, including 16 affected males out of 48 males at risk for the disease, most of whom were seen by one of us (PA). Affected males are blind with no associated symptoms and apparently are not mentally retarded.

[Prenatal virus infections and orofacial clefts].

A potential teratogenic activity of virus infections caused by the viruses of rubella, influenza, parotitis, hepatitis B, cytomegalovirus and the Epstein-Barr virus was investigated. Specific antibodies against these viruses were examined serologically in children with orofacial clefts and in their mothers and the results were compared with those obtained in control children and their mothers. Different micromethods were used in performing the examinations (ELISA, RIA, NIR, KFR, HIT).

[Genetic counseling in prenatal diagnosis of cystic fibrosis].

In this paper we discuss the possible results of post- and prenatal DNA-diagnosis in cystic fibrosis with respect to the modification of the risk of having an affected child, depending on how closely the affected patient is related to those seeking advice. For parents with an affected child post- and prenatal DNA-diagnosis yields very reliable results and is an important factor in their decision process. In contrast to this, DNA-diagnosis for other relatives or individuals without an affected family member can lead to results which may intensify conflicts of decision making.

Aldosterone deficiency II (CMO II deficiency) is not the result of a mutation of an MspI restriction site within the CYP11B gene.

We report our investigations of a German family with aldosterone deficiency (CMO II deficiency). Restriction fragment length polymorphism analysis using a P450c11 probe demonstrates that a MspI restriction site mutation within the CYP11B gene cannot be the underlying cause for this defect, as has been suggested previously.

New mutation versus exclusion at the alpha-1-antitrypsin locus: a multifaceted approach in a problematical paternity case.

In a case of disputed paternity with overwhelming indications of fatherhood for the putative father, as supported by serological tests and biostatistical evaluation, a classical exclusion constellation was found at the alpha 1-antitrypsin (PI) locus: mother PI M1; child PI M1M3, and putative father PI M1M2. Additional studies included PI oligonucleotide phenotyping and DNA fingerprint analysis. Results from the entire data set led us to assume a rare genetic event at the paternal PI locus.

Serological H-Y antigen and gonadal status in XYDOM sex-reversed mice.

Y chromosomes of feral mice (Mus musculus domesticus) from various localities, when introduced into the C57BL/6 laboratory strain, give rise to phenotypic females and true hermaphrodites both with the sex chromosome constellation XY. Sex-reversed animals of each type were examined macroscopically or histologically for gonadal status and H-Y antigenic activity by serological assay methods. Most XY females with histologically confirmed bilateral ovaries did not differ from XX female controls with respect to serological H-Y antigen, i.

Serological H-Y antigen in the female chicken occurs during gonadal differentiation.

In the chicken, serological H-Y antigen is specific for the female sex. Male gonad differentiation can be experimentally influenced by estrogens, resulting in the transient formation of an ovotestis. The sex-inverted gonad becomes positive for H-Y antigen.

Absence of Y-specific DNA sequences in human 46,XX true hermaphrodites and in 45,X mixed gonadal dysgenesis.

A search for Y-specific DNA sequences has been performed in a sample of seven 46,XX true hermaphrodites and one 45,X mixed gonadal dysgenesis case and compared with a sample of 11 XX males. Using six Y-specific DNA probes no hybridization signal was obtained in the hermaphrodite group; in contrast, all XX males gave a positive signal with at least one probe. This difference is statistically highly significant.

Linkage studies in a pedigree with Van der Woude syndrome.

A kindred segregating for Van der Woude syndrome (VWS) through five generations is described. Biochemical and serological phenotypes at 36 polymorphic marker loci have been determined, of which 27 were informative for linkage analysis to the VWS gene (LIPED 3 computer programme). Lod scores are reported and show exclusion of close linkage for most of the marker loci.

The occurrence of serological H-Y antigen (Sxs antigen) in the diandric protogynous wrasse, Coris julis (L.) (Labridae, Teleostei).

The serological sex-specific (Sxs) antigen (previously called 'H-Y antigen') has been shown, in various vertebrate species ranging from fish to mammals, to be characteristic of the heterogametic sex. We studied a protogynous hermaphrodite, Coris julis, in order to examine whether the change of a female to a secondary male also involves a change in the Sxs-antigen phenotype. The (homogametic) females of this species were found to be Sxs negative, while both primary and secondary males were Sxs positive.

Coagulation factor XIII: genetic linkage studies with F13B.

Linkage relations of the F13B gene with 38 marker genes are analyzed, which, along with the data of earlier reports on the same subject, brings the number of comparisons to a total of 49. Practically all the lod scores are totally negative. This will mean that the F13B gene can hardly be located on the chromosomes/chromosome arms 1p, 2p, 4q, 6p, 14p, 15p, 20q, 21p, 22 and also not on longer segments of 3q, 6q, 7q, 9p, 9q, 11q, 13q, 14q, 16p, and 16q.

Serologically H-Y antigen-negative XO mice.

In a series of six independent experiments organ homogenates of 35 mice of the XX, XO or XY sex chromosome constitutions were absorbed using three different anti-H-Y antisera raised in inbred female LEW rats. Residual activities of absorbed antisera were tested in the Raji cell, complement-dependent, cytotoxicity test. Homogenates of various tissues, including the gonads, of XX and XO females were equally unable to absorb H-Y antibodies, indicating that tissues of these mice do not carry the H-Y antigen.

A male with a monocentric Yq isochromosome and presence of a Yp-specific DNA sequence.

We describe clinical features and laboratory findings in a physically and mentally retarded male with underdeveloped testes, a seemingly monocentric isochromosome of Yq but the presence of a Yp-specific DNA sequence at a single dose of unknown genomic localisation, and the presence of H-Y antigen at normal male titer. Our data contribute to the fine mapping of the human Y chromosome by correlating phenotypic features with results from karyotypic, immunologic, and molecular hybridisation analyses.

Virilization without adrenal hyperplasia in 21-hydroxylase deficiency during fetal life.

The characteristic excess production of androgens in the cortisol 21-hydroxylase defect is generally considered to be secondary to ACTH stimulation of alternate pathways. Whenever a morphological examination of the adrenals has been possible in this disorder, adrenocortical hyperplasia was a constant finding. The availability of methods for the prenatal diagnosis of the 21-hydroxylase defect has made it possible to examine some of the manifestations of this disorder during fetal life.

The X linked recessive form of XY gonadal dysgenesis with a high incidence of gonadal germ cell tumours: clinical and genetic studies.

Five phenotypic females in one family had the genotype 46,XY and all had gonadal germ cell tumours. Studies of the family pedigree suggest that this form of XY gonadal dysgenesis is inherited in an X linked recessive manner. G banding of elongated metaphase chromosomes from two subjects with XY gonadal dysgenesis and a female carrier showed no aberrations of the X chromosome.

Presence of H-Y antigen in female patients with sex-chromosome mosaics and absence of testicular tissue.

H-Y antigen was tested in five women with sex chromosome mosaicism and gonadal streaks. Three patients had a 45,X/46,XY or 46,X,der(Y) and two a 45,X/46,X, der(X) chromosome constitution. All patients were H-Y antigen positive.