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Biomedical subjects

J Horst

Publications and source records attributed to J Horst.

At least 73 records · Page 4Linked to original sources
PubMed1996

Analysis of unstable DNA sequence in FMR1 gene in Polish families with fragile X syndrome.

The unstable DNA sequence in the FMR1 gene was analyzed in 85 individuals from Polish families with fragile X syndrome in order to characterize mutations responsible for the disease in Poland. In all affected individuals classified on the basis of clinical features and expression of the fragile site at X(q27.3) a large expansion of the unstable sequence (full mutation) was detected. About 5% (2 of 43) of individuals with full mutation did not express the fragile site. Among normal alleles, ranging in size from 20 to 41 CGG repeats, allele with 29 repeats was the most frequent (37%). Transmission of premutated and fully mutated alleles to the offspring was always associated with size increase. No change in repeat number was found when normal alleles were transmitted.

Alleles↗
PubMed1995

Factor VIII gene inversions in severe hemophilia A: results of an international consortium study.

Twenty-two molecular diagnostic laboratories from 14 countries participated in a consortium study to estimate the impact of Factor VIII gene inversions in severe hemophilia A. A total of 2,093 patients with severe hemophilia A were studied; of those, 740 (35%) had a type 1 (distal) factor VIII inversion, and 140 (7%) showed a type 2 (proximal) inversion. In 25 cases, the molecular analysis showed additional abnormal or polymorphic patterns. Ninety-eight percent of 532 mothers of patients with inversions were carriers of the abnormal factor VIII gene; when only mothers of nonfamilial cases were studied, 9 de novo inversions in maternal germ cells were observed among 225 cases (approximately 1 de novo maternal origin of the inversion in 25 mothers of sporadic cases). When the maternal grandparental origin was examined, the inversions occurred de novo in male germ cells in 69 cases and female germ cells in 1 case. The presence of factor VIII inversions is not a major predisposing factor for the development of factor VIII inhibitors; however, slightly more patients with severe hemophilia A and factor VIII inversions develop inhibitors (130 of 642 [20%]) than patients with severe hemophilia A without inversions (131 of 821 [16%]).

Blotting, Southern↗
PubMed1995

Parental origin of the extra haploid chromosome set in triploidies diagnosed prenatally.

The parental origin of the additional chromosome complement in a total of 17 cases of triploidy was determined mainly using highly polymorphic microsatellites. Maternal origin of the triploidy was demonstrated in most cases. To the best of our knowledge, this is the first systematic evaluation of the parental origin of chromosome sets in fetuses who survived until a cytogenetic diagnosis was established. In contrast to previous investigations this study documented a predominance of maternal origin of the extra haploid set mainly due to longer survival time for digynic triploidies. The concept of 2 distinct fetal phenotypes in triploidy is clearly supported by this study.

Adult↗
PubMed1995

Two polymorphic dinucleotide repeats in intron 44 of the dystrophin gene.

Duchenne muscular dystrophy (DMD) is one of the most common and severe X-linked disorders with an incidence of approximately 1 in 3500 newborn males. In more than 60% of DMD patients, deletions of part or all of the dystrophin gene have been shown. Despite this, carrier detection still poses a problem in some cases, because of the enormous size of the gene and the lack of sufficient numbers of informative markers. Here, we report the isolation and characterization of two additional microsatellite markers (IVS44SK12 and IVS44SK21) in intron 44 of the dystrophin gene. Both markers are useful for carrier detection either by indirect DNA analysis or by direct proof of loss of heterozygosity.

Base Sequence↗
PubMed1995

Genetic heterogeneity of polycystic kidney disease in Bulgaria.

Linkage analysis was performed on 22 Bulgarian families with polycystic kidney disease (PKD) ascertained through the hemodialysis centers of two medical schools. A total of 128 affected and 59 unaffected individuals, and 54 spouses have been investigated using eight polymorphic markers linked to PKD1 and nine markers to PKD2. The results demonstrate locus heterogeneity with 0.67 as the maximum likelihood value of alpha, i.e., the proportion of families linked to PKD1. In five families, the results suggest linkage to PKD2 and observed recombinants place the gene between loci D4S1544 and D4S1542. In one family, two double recombinants for closely linked markers on chromosome 16 and on chromosome 4 give evidence for the lack of linkage to either PKD1 or PKD2, thus suggesting the involvement of a third locus. Analysis of clinical data in the PKD1 group versus the unlinked group shows no significant differences in the severity of the disease.

Adult↗
PubMed1995

Genetic risk in micromanipulative assisted reproduction.

The empirical data on pregnancy outcome after intracytoplasmic sperm injection (ICSI) are encouraging, but still insufficient to rule out definitely adverse genetic or teratological effects. We analyse potential adverse effects of ICSI by applying general principles of genetic and teratological risk assessment. The role of gamete micromanipulation as a possible teratogen is discussed. We consider whether ICSI patients are at increased risk for carrying and propagating genetic lesions of different kinds. The possible interference of ICSI with genomic imprinting and pre-zygotic sperm selection is reviewed and we discuss the potentially protective role of DNA repair in oocytes. Considering the available empirical data and the conclusions from our theoretical analysis it appears that neither lassitude nor over-concern about adverse effects of ICSI are justified.

Congenital Abnormalities↗
PubMed1995

Congenital heart disease in the 48,XXYY syndrome.

We report on an infant with severe tetralogy of Fallot, bilateral preauricular pits, and a 48,XXYY chromosomal complement. This case and evidence collected from the literature suggest that congenital heart disease may occur in the 48,XXYY syndrome more frequently than currently appreciated.

Heart Defects, Congenital↗
PubMed1995

Smith-Lemli-Opitz syndrome diagnosed by using time-of-flight secondary-ion mass spectrometry.

We describe a rapid and sensitive method involving time-of-flight secondary-ion mass spectrometry (TOF-SIMS) for specific laboratory diagnosis of the Smith-Lemli-Opitz syndrome, which is characterized by massive (approximately 1000-fold) accumulation of the biosynthetic cholesterol precursor 7-dehydrocholesterol. Minute amounts of blood (1-50 microL) were extracted with n-hexane, and aliquots were analyzed by TOF-SIMS. 7-Dehydrocholesterol and its isomers were detected at 491.3 mass units ([M + 107Ag]+) and cholesterol at 495.3 mass units ([M + 109Ag]+). Quantitation of 7-dehydrocholesterol and cholesterol was achieved after saponification and addition of stigmasterol as internal standard. Whereas 7-dehydrocholesterol and isomeric dehydrocholesterol were not detectable in controls, the patients revealed concentrations ranging between 0.84 and 1.25 mmol/L. Comparison with results obtained by gas chromatography indicated that quantitation by TOF-SIMS yielded the sum of 7-dehydrocholesterol, isomeric dehydrocholesterol II, and sterol III, the latter two also being increased in the patients. Consistent with quantitation by gas chromatography, the cholesterol concentrations in the patients ranged between 1.54 and 2.12 mmol/L (controls: 6.10 +/- 1.37 mmol/L).

Cholesterol↗
PubMed1994

Nonisotopic detection of mutations using a modified single-strand conformation polymorphism analysis.

This report describes a rapid convenient screening system with improved sensitivity to detect mutations in the cystic fibrosis transmembrane regulator (CFTR) gene based on nonisotopic SSCP analysis. Because conventional SSCP analysis is often hampered by poor yield of single-stranded DNA, we applied the well-established solid-phase technique in which streptavidin-coated magnetic beads are used to immobilize biotinylated polymerase chain reaction (PCR) products. High yield of single-stranded DNA can be eluted from the solid phase by denaturation and used for SSCP analysis. An additional advantage of this procedure is that the immobilized single strand is available without any further purification steps for solid-phase sequencing.

Base Sequence↗
PubMed1994

Frequencies of the most common mutations responsible for phenylketonuria in Poland.

We screened 91 Polish phenylketonuric (PKU) children for the presence of 18 common mutations in the phenylalanine hydroxylase (PAH) gene, and 75.7% of PAH alleles were identified. The R408W mutation accounted for 54.9% of PAH mutant alleles. In the other 20.8%, eight mutations were detected: R158Q (6.6%), IVS10 (4.9%), IVS12 (2.7%), R261Q (2.2%), G272ter (1.65%), Y414C (1.1%), R252W (1.1%) and P281L (0.54%). Correlations between genotype and clinical phenotype were described.

Alleles↗
PubMed1994

Factor VIII gene inversions causing severe hemophilia A originate almost exclusively in male germ cells.

The factor VIII gene, which is defective in hemophilia A, is located in the last megabase of the long arm of the X chromosome. Inversions due to intrachromosomal homologous recombination between mispaired copies of gene A located within intron 22 of the gene and about 500 kb telomeric to it account for nearly half of all cases of severe hemophilia A. We hypothesized that pairing of Xq with its homolog inhibits the inversion process, and that, therefore, the event originates predominantly in male germ cells. In all 20 informative cases in which the inversion originated in a maternal grandparent, DNA polymorphism analysis determined that it occurred in the male germline. In addition, all but one of 50 mothers of sporadic cases due to an inversion were carriers. Thus, these data support the hypothesis and indicate that factor VIII gene inversions leading to severe hemophilia A occur almost exclusively in male germ cells.

Blotting, Southern↗
PubMed1993

[Mutation in the cystic fibrosis transmembrane-regulator gene in bilateral congenital ductus deferens aplasia].

A 28-year-old man and his 27-year-old wife were investigated for infertility of 3 1/2 years' duration. There was azoospermia caused by bilateral aplasia of the vas deferens, and therefore it was planned to aspirate spermatozoa from the epididymis for the purpose of in-vitro fertilisation. As part of the diagnostic workup the man was investigated for those mutations of the cystic fibrosis transmembrane regulator (CFTR) gene which occur with undue frequency in association with aplasia of the vas deferens. Deoxyribonucleic acid (DNA) analysis revealed a typical three base deletion (delta F 508). In the wife, CFTR gene mutations were excluded with 80% probability. The likelihood of cystic fibrosis in this couple's children was accordingly estimated to be about 0.2%--an acceptable risk. Assisted fertilization in patients with bilateral aplasia of the vas deferens should not be undertaken until they have been thoroughly investigated and informed of the risks.

Adult↗