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D J Halley

Publications and source records attributed to D J Halley.

At least 91 records · Page 5Linked to original sources
PubMed1993

Mental status and fragile X expression in relation to FMR-1 gene mutation.

The fragile X mental retardation syndrome is caused by unstable expansion of a CGG repeat in the FMR-1 gene. Clinical expression is associated with a large expansion of the CGG repeat. The mutation in the FMR-1 gene and the cytogenetic expression of the fragile site at Xq27.3 have been studied in 52 fragile X male patients. The percentage of the cytogenetic expression of the fragile site at Xq27.3 positively correlates with the mean size of the full mutation in the FMR-1 gene (p < 0.0001) irrespective of the presence of additional premutation alleles. We noted a less frequent occurrence of additional premutation alleles in adult patients compared with juveniles, suggesting a continued mitotic instability in life. Additionally, the level of mental retardation has been ascertained in 35 patients using the Stanford-Binet or Terman-Merrill test of general intelligence. The presence of a full mutation in the FMR-1 gene seemed decisive for the occurrence of mental impairment in the patient. No correlation is observed between the degree of mental retardation and the size of the full mutation. The degree of mental retardation seemed not to be influenced by the presence of premutation alleles in part of the cells in addition to a full mutation. One patient is described with the 'Prader-Willi-like' subphenotype of the fragile X syndrome, showing a deletion in the FMR-1 gene in a part of his cells in addition to a full mutation.

Adult↗
PubMed1992

Family studies of the steroid 21-hydroxylase and complement C4 genes define 11 haplotypes in classical congenital adrenal hyperplasia in The Netherlands.

Two steroid 21-hydroxylase genes are normally present within the human major histocompatibility complex near the genes encoding the fourth component of complement (C4A and C4B). Steroid 21-hydroxylase is encoded by the CYP21 gene, while the highly homologous CYP21P gene is a pseudogene. We studied steroid 21-hydroxylase and complement C4 haplotypes in 33 Dutch patients (29 families) suffering form classical congenital adrenal hyperplasia (CAH) and in their 80 family members, and also in 55 unrelated healthy controls, using 21-hydroxylase and complement C4 cDNA probes. Eleven different haplotypes, defined in terms of gene deletions, gene duplications, conversions of CYP21 to CYP21P, and "long" and "short" C4 genes, were found. In 23% of the patients' haplotypes, the CYP21 gene was deleted; in 12%, it was converted into a CYP21P pseudogene. In the remaining 65%, the defect was apparently caused by a mutation not detectable by this method. The most common haplotype (with one CYP21 and one CYP21P gene) was significantly more often observed in patients with simple virilizing CAH than in those with salt-losing CAH. Comparison of the 21-hydroxylase haplotypes found in CAH patients from several countries shows evidence for considerable genetic variation between the groups studied.

Adrenal Hyperplasia, Congenital↗
PubMed1992

Computer simulation of linkage and heterogeneity in tuberous sclerosis: a critical evaluation of the collaborative family data.

The existence of locus heterogeneity for a genetic disease may complicate linkage studies considerably, especially when very few large families with the disease are available. In this situation a modest collection of families is unlikely to be sufficient for successful localisation of one or more disease genes. Recently, eight research groups working on tuberous sclerosis (TSC) brought together linkage data pertaining to the candidate chromosomes 9, 11, and 12 for a large group of families. In a series of simulation studies we determined the probability of detecting linkage and linkage heterogeneity in this set of families. On average TSC families are very small; in most cases there are fewer than two informative meioses. The size distribution of chromosome 9 linked families was similar to that of non-linked families. This indicates that a dramatic difference in the clinical severity of major genetic forms of TSC is unlikely. The results of our simulation studies show that this set of families can generate highly significant evidence for linkage and heterogeneity. When two TSC genes are equally common, the strongest evidence for linkage and heterogeneity could be obtained using a method based on the incorporation of multiple candidate regions in a single analysis, with an average lod score of 24.27.

Chromosome Mapping↗
PubMed1991

DNA analysis in patients with lissencephaly type I and other cortical dysplasias.

DNA markers YNZ22.1, YNH37.3, 144D6, and VAW508 were studied in five patients with the Miller-Dieker syndrome, 17 patients with the isolated lissencephaly sequence, one patient with a non-classified lissencephaly, and nine patients with an atypical cortical dysplasia. All patients had normal chromosomes except for a deletion 17p13.3 in one of the five Miller-Dieker patients. The five Miller-Dieker patients showed deletions of markers YNZ22.1 and YNH37.3 in contrast to the other patients tested. In one patient, the deletion was in the maternally contributed chromosome. Prenatal diagnosis by DNA analysis allowed exclusion of the recurrence of Miller-Dieker syndrome in a subsequent pregnancy.

Brain↗
PubMed1991

Isolated lissencephaly sequence associated with a microdeletion at chromosome 17p13.

DNA markers YNZ22.1, YNH37.3, 144D6 and VAW508 were studied in a patient with the isolated lissencephaly sequence (ILS). A normal karyotype was found in the patient. The DNA of the patient showed deletions of markers YNZ22.1 and YNH37.3. This is the first report of a case of ILS (with grade 3 lissencephaly) with a submicroscopic deletion. The presence of a microdeletion in 17p13 in an ILS patient indicates that Miller-Dieker syndrome and ILS have a common etiology.

Blotting, Southern↗
PubMed1990

[Carrier detection in relatives of patients with cystic fibrosis and their partners].

In the clinical genetics centres of Groningen and Rotterdam carrier detection by means of DNA analysis was performed in 55 relatives of cystic fibrosis patients at their request; 32 of them were siblings, 22 were uncles and aunts, and one was a first cousin. In 31 of them carriership could be demonstrated. Carrier detection was also performed in 23 of their partners, in 3 partners of female CF patients, and in 4 AI donors. In one of the partners of the carriers carriership was demonstrated also. This is the first couple in The Netherlands to whom information on the 25% risk of CF in a future child and on the corresponding reproductive options could be given prior to the birth of a first affected child. Since not all mutations of the CF gene are detectable with present methods, carrier detection still has its restrictions, which are discussed.

Adult↗
PubMed1990

The cystic fibrosis defect approached from different angles--new perspectives on the gene, the chloride channel, diagnosis and therapy.

The search for the basic defect in cystic fibrosis (CF) has reached a decisive stage since the recent identification of the responsible gene. Electrophysiological and biochemical research had defined the CF defect as a dysregulation of epithelial chloride channels. The putative protein product of the now identified gene shares properties with other known transport proteins, but it is not necessarily itself a chloride channel protein. Elucidation of the primary cellular defect will certainly have important aetiological and hopefully therapeutic implications. The identification of the major gene mutation already has significant consequences for genetic counselling and prenatal diagnosis. Heterozygote detection at the population level awaits identification of the probably heterogenous mutations on about 30% of the CF chromosomes. At present, about 50% of CF patients are homozygous for the recently identified major CF mutation.

Chlorides↗
PubMed1990

The mutation delta F508 on Dutch cystic fibrosis chromosomes: frequency and relation to patients age at diagnosis.

We tested 190 chromosomes from Dutch cystic fibrosis (CF) patients and carriers for the presence or absence of the major CF mutation delta F508. This mutation was found on 77% of the Dutch CF chromosomes. We observed a significant difference in the distribution of the ages at diagnosis between homozygotes for delta F508 and the other patients. delta F508 homozygotes tend to be identified as patients at neonatal or infantile age. The age at diagnosis of patients with at least one unknown allele, on the other hand, ranged between neonatal and young adult age.

Adolescent↗
PubMed1990

Genetic heterogeneity in tuberous sclerosis.

Tuberous sclerosis (TSC) is an autosomal dominant disorder characterized by widespread hamartosis. Preliminary evidence of linkage between the TSC locus and markers on chromosome 9q34 was established, but subsequently disputed. More recently, a putative TSC locus on chromosome 11 has been suggested and genetic heterogeneity seems likely. Here we describe an approach combining multipoint linkage analysis and heterogeneity tests that has enabled us to obtain significant evidence for locus heterogeneity after studying a relatively small number of families. Our results support a model with two different loci independently causing the disease. One locus (TSC1) maps in the vicinity of the Abelson oncogene at 9q34 and a second locus (TSC2) maps in the region of the anonymous DNA marker Lam L7 and the dopamine D2 receptor gene at 11q23.

Chromosome Mapping↗
PubMed1990

New polymorphic DNA marker close to the fragile site FRAXA.

DNA from a human-hamster hybrid cell line, 908-K1B17, containing a small terminal portion of the long arm of the human X chromosome as well as the pericentric region of 19q was used as starting material for the isolation of an X-chromosome-specific DNA segment, RN1 (DXS369), which identifies a XmnI RFLP. Linkage analysis in fragile X families resulted in a maximum lod score of 15.3 at a recombination fraction of 0.05 between RN1 and fra(X). Analysis of recombinations around the fra(X) and distal to DXS105. Analysis of the marker content of hybrid cell line 908K1B17 suggests the localization of RN1 between DXS98 and fra(X). Heterozygosity of DXS369 is approximately 50%, which extends the diagnostic potential of RFLP analysis in fragile X families significantly.

Animals↗
PubMed1989

Prenatal diagnosis and genetic counseling of cystic fibrosis.

The number of DNA markers at the chromosome 7-locus of the putative CF gene has markedly increased in recent years, also as a result of intensive research into the possible "candidate" gene. In studies of families with one or more affected children, 97.5% of families are now fully informative, allowing a prenatal diagnosis by chorionic villus sampling in the 10th week and DNA-analysis, which will usually give now a diagnosis with a remaining risk of less than 1%. The microvillar enzyme test in amniotic fluid after amniocentesis in the 18th week will remain an alternative for couples who have a high prior risk, but are either not informative at DNA analysis, or where no information on a (deceased) index case (previous affected child) is available. The risk for a wrong classification is in the order of a few percent (in a 1:4 prior risk case) and careful discussion of the limitations are needed when this test is applied to cases with a lower prior risk. The linkage disequilibrium established for a number of RFLP's (Restriction Fragment Length Polymorphisms), as detected by various probes and various restriction enzymes around the CF locus has opened the possibility to refine the risk estimation of heterozygosity for individuals outside families with CF-affected children. The presence of certain haplotypes may change the risk for being CF heterozygote from +/- 1:7 to 1:250, as compared to a population risk of +/- 1:25.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromosomes, Human, Pair 7↗
PubMed1988

Cystic fibrosis: screening for a DNA deletion by field inversion gel electrophoresis.

We analyzed DNA of ten cystic fibrosis (CF) patients representing DNA of 19 different CF chromosomes and screened for deletions by means of field inversion gel electrophoresis (FIGE). No differences were detected after digestion of the DNA samples with the restriction enzymes Not I and Sfi I and hybridization with the probes MetH, MetD, J3.11, and 7C22. Thus the percentage of deletions occurring within the CF region and detectable with FIGE is less than 15.2% (95% confidence interval, N = 19).

Chromosome Deletion↗
PubMed1984

Regional mapping of the human gene for lysosomal alpha-glucosidase by in situ hybridization.

The current approach to the chromosomal localization of genes coding for lysosomal enzymes has been the correlation of enzymatic and karyotypic analyses of human-rodent somatic cell hybrids. The feasibility of regional mapping depends on the availability of human cells with informative chromosomal rearrangements. In this communication we report the first localization of a gene coding for a lysosomal enzyme by in situ hybridization. The application of an acid alpha-glucosidase cDNA probe to normal human chromosomes allowed direct regional mapping of the alpha-glucosidase locus (GAA) to the region q23----q25 of chromosome 17.

Chromosome Mapping↗