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J Horst

Publications and source records attributed to J Horst.

At least 55 records · Page 3Linked to original sources
PubMed1998

Strong preference for non-invasive prenatal diagnosis in women pregnant through intracytoplasmic sperm injection (ICSI)

Intracytoplasmic sperm injection (ICSI) is a new and most powerful technique to treat severe forms of human infertility. While the follow-up studies have not shown an increased malformation risk so far, the genetic implications of ICSI are still not fully understood. For this reason, many institutions routinely recommend or even enforce invasive prenatal tests after successful intracytoplasmic sperm injection. We have counselled 107 women pregnant through ICSI about prenatal diagnosis. Sixty-five had already received genetic counselling prior to the treatment (group 1), while 42 had not attended our clinic before (group 2). They were free to choose between invasive and non-invasive diagnosis or no prenatal tests at all. Fifty-four per cent of these patients had an indication for prenatal karyotyping or other invasive procedures independent of ICSI. Only 17 per cent of the total cohort made use of amniocentesis or fetal blood sampling, 82 per cent opted for non-invasive tests (ultrasound, serum screening), and one couple did not wish any prenatal studies. The preference for non-invasive procedures was stronger in group 1 (94 per cent) than in group 2 (65 per cent). We suggest that if patients pregnant through ICSI have the option to choose freely between invasive and non-invasive prenatal tests, they strongly favour the latter.

Adult↗
PubMed1997

Application of the Surface Complex Formation Model to Ion Exchange Equilibria

The surface complexation model as previously applied to pure anion and pure cation exchange equilibria has been extended to the description of the amphotheric sorption of inorganic ions onto activated alumina. Logarithmic equilibrium parameters (generalized separation factors) can be calculated from equilibrium concentrations in simple systems for the sorption of anions and cations. Both separation factors are functions of the oxide loading composition. Plotting the separation factors vs the loading compositions yields a set of two sorption constants for each kind of ion. The major advantage of the theoretical approach is that these constants can be applied without any adaptation to the prediction of multicomponent systems. Evaluation of experiments with two commercially available activated alumina products demonstrate the validity of the approach. The equilibrium of multicomponent systems can be predicted with excellent accuracy by means of the parameters for the uptake of chloride, nitrate, sulfate, sodium, and potassium ions. Copyright 1997 Academic Press. Copyright 1997Academic Press

Journal Article↗
PubMed1997

The genomic organization and the full coding region of the human PAX7 gene.

The PAX7 gene encodes a transcription factor that is a member of the PAX family of developmental control genes. In addition to playing a role in embryogenesis, PAX genes appear to be of importance in a number of diverse human diseases and cancers. The PAX7 gene maps to human chromosomal region 1p36 and therefore is a potential candidate for human disorders linked to this region. In particular, a rearrangement of the PAX7 gene by chromosomal translocation is frequently found in alveolar rhabdomyosarcoma tumors. Here, we cloned a cDNA containing the full coding region of the human PAX7 gene and determined its genomic organization. The gene encodes a predicted protein of 520 amino acids that is 47 amino acids longer at the carboxy end than the highly related PAX3 protein. The coding region of the gene is interrupted by seven introns, the positions and lengths of which are similar to those of the corresponding introns of the PAX3 gene. Sequence data for exon/intron boundaries of PAX7 exons 1, 5, 6, 7, and 8 were determined and, together with previously published data for exons 2, 3, and 4, provide the complete sequence information for mutation analysis of the human PAX7 gene.

Amino Acid Sequence↗
PubMed1997

Magnesium toxicosis in two horses.

Magnesium sulfate, a saline laxative, is often used for treatment of intestinal impactions in horses. Clinical signs of hypermagnesemia are an uncommon complication following oral administration of magnesium sulfate. Overdose of magnesium sulfate in combination with renal insufficiency, hypocalcemia, or compromise of intestinal integrity may predispose horses to magnesium toxicosis. Establishment of diuresis with fluids and IV administration of calcium may provide successful treatment of magnesium toxicosis in horses.

Animals↗
PubMed1997

The genomic organization of the murine Pax 8 gene and characterization of its basal promoter.

Lambda phage clones containing the murine Pax 8 gene were isolated from a C57BL/6 kidney genomic mouse library using mouse cDNA fragments as probes. A clone encompassing about 16 kb of the 5' untranslated region of the murine Pax 8 gene was isolated from a mouse embryonic stem cell (D3) library. The murine Pax 8 gene has a size of approximately 26 kb and contains the coding sequence for mRNA in 12 exons. The major and several minor transcription initiation sites were identified. Position +1 is located 488 nucleotides upstream of the ATG initiation codon and 24 bases downstream of a TATA-like sequence, ATAAAA. The translation initiation and termination sites are located in exons 2 and 12, respectively. Further analysis of 570 bases of the 5' flanking sequence revealed AP2, SP1, PEA3, zeste, NF-kappaB, and CCAAT consensus binding sites. Ribonuclease protection assays with a probe spanning the first two exons of mouse Pax 8 cDNA on total RNA samples isolated from different tissues of newborn mice show that the murine Pax 8 gene is predominantly expressed in kidney tissue. Low levels of Pax 8 gene expression were also found in the liver, spleen, lung, brain, and heart. The same transcription initiation sites are utilized in different tissues of newborn mice and embryo at Day 10.5 postconception. A FISH assay shows that the murine Pax 8 gene is located on chromosome 2, map position B.

Animals↗
PubMed1997

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. Of the CAVD patients, 75% carried CFTR mutations or disease-associated CFTR variants, such as the "5T" allele, on both chromosomes. The distribution of mutation genotypes clearly differed from that observed in cystic fibrosis. None of the CAVD patients was homozygous for delta F508 and none was compound heterozygous for delta F508 and a nonsense or frameshift mutation. Instead, homozygosity was found for a few mild missense or splicing mutations, and the majority of CAVD mutations were missense substitutions. Twenty-one German CAVD patients were compound heterozygous for delta F508 and R117H, which was the most frequent CAVD genotype in our study group. Haplotype analysis indicated a common origin for R117H in our population, whereas another frequent CAVD mutation, viz. the "5T allele" was a recurrent mutation on different intragenic haplotypes and multiple ethnic backgrounds. We identified a total of 46 different mutations and variants, of which 15 mutations have not previously been reported. Thirteen novel missense mutations and one unique amino-acid insertion may be confined to the CAVD phenotype. A few splice or missense variants, such as F508C or 1716 G-->A, are proposed here as possible candidate CAVD mutations with an apparently reduced penetrance. Clinical examination of patients with CFTR mutations on both chromosomes revealed elevated sweat chloride concentrations and discrete symptoms of respiratory disease in a subset of patients. Thus, our collaborative study shows that CAVD without renal malformation is a primary genital form of cystic fibrosis in the vast majority of German patients and links the particular expression of clinical symptoms in CAVD with a distinct subset of CFTR mutation genotypes.

Adult↗
PubMed1997

Mutational analysis of ectopic factor VIII transcripts from hemophilia A patients: identification of cryptic splice site, exon skipping and novel point mutations.

Mutational analysis of the gene for clotting factor VIII is complicated by its large size, the high frequency of de novo mutations and its tissue-specific expression. In order to facilitate the search for mutations, we have used a combination of reverse transcription-polymerase chain reaction (RT-PCR) of ectopic factor VIII transcripts, PCR of genomic DNA, single-strand conformation polymorphism analysis and direct sequencing. Here we describe the characterization of seven potentially pathogenic mutations: five of them are novel and the reason for the pathogenicity of the sixth could be determined. Here cDNA analysis revealed the absence of the first 47 bp of exon 16 in approximately 80% of the processed factor VIII mRNA, likely due to activation of a cryptic acceptor splice site within exon 16. The other novel mutations reported here include the skipping of exon 19, which predicts the removal of the corresponding 39 amino acids from the A3 domain, and four missense mutations: W14G, Y620C, W1889L, and Q2087R.

DNA Mutational Analysis↗
PubMed1997

Alternative splicing in PAX2 generates a new reading frame and an extended conserved coding region at the carboxy terminus.

PAX2 is a member of the PAX multigene family encoding transcription factors active in specific tissues during embryogenesis. Several PAX/Pax genes (PAX and Pax describe homologous genes in human and mice, respectively) have been shown to possess critical morphogenetic functions as identified by the analysis of mice targeted for Pax genes and the phenotype of patients heterozygous for PAX mutations. Mutations in PAX2 have been shown to be implicated in independent cases of renal-coloboma syndrome. Here, we report the characterisation of a new PAX2 isoform, viz. PAX2d, which arises because of the use of an alternative acceptor splice site within exon 12 of the PAX2 gene; this leads to a shift in the reading frame. A conserved coding region extended over the regular stop codon may emphasize the biological significance of this isoform.

Alternative Splicing↗
PubMed1997

Screening for deletions of the Y chromosome involving the DAZ (Deleted in AZoospermia) gene in azoospermia and severe oligozoospermia.

OBJECTIVE: To evaluate the occurrence and prevalence of microdeletions of the Y chromosome involving the DAZ (Deleted in AZoospermia) gene in patients with azoospermia or severe oligozoospermia. DESIGN: Controlled clinical study. SETTING: University infertility clinic. PATIENT(S): Infertile men (n = 168) with nonobstructive, idiopathic azoospermia or severe oligozoospermia and normal LH. The control group consisted of proven fathers (n = 86). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Semen analysis; polymerase chain reaction amplification of the loci sY84, sY143, sY254, and sY255; serum FSH, LH, and T; testicular volume. RESULT(S): Deletions involving the sY254 and sY255 DAZ loci were found in three azoospermic patients and two men with sperm concentration < 1 x 10(6)/mL. Serum FSH was elevated in four patients and was normal in one. All five patients had decreased testicular volumes compared with controls. No deletions involving the sY84 and sY143 loci were found. The four loci were amplified normally in the control group. CONCLUSION(S): The estimated frequency of deletions involving the DAZ locus is 3% in azoospermic-severely oligozoospermic men consulting an infertility clinic. Polymerase chain reaction amplification of the DAZ locus is useful for the diagnosis of microdeletions of the Y chromosome. Deletions involving more proximal regions of the Y chromosome seem to be rare.

Adult↗
PubMed1997

Sex chromosomal anomalies in pregnancies conceived through intracytoplasmic sperm injection: a case for genetic counselling.

The prevalence of sex chromosomal anomalies (SCA) is higher after treatment with intracytoplasmic sperm injection (ICSI) than in naturally conceived pregnancies. This finding is not only important in the debate about the genetic safety of ICSI, it also has repercussions on the design of appropriate strategies for prenatal and preimplantation diagnosis in ICSI pregnancies. We discuss here in detail the developmental prognosis of individuals carrying a sex chromosomal anomaly. Major malformations do occur in Turner syndrome, but not so in Klinefelter, the triple X and the XYY syndromes. Infertility represents an almost obligate finding in Klinefelter syndrome, but the latest developments in microassisted reproduction may help to overcome this problem. Importantly, mental retardation does not occur more often in individuals with an SCA than in normal controls. Academic achievement, however, may be somewhat reduced compared with peers. Overall, for most children carrying a sex chromosomal anomaly, a major congenital handicap is not to be expected, and the long-term developmental prognosis is fairly good. Therefore, if an SCA is diagnosed prenatally in an ICSI pregnancy, an unbiased and detailed discussion of the developmental perspectives is warranted. The option of continuing such a pregnancy should be given due consideration.

Cytoplasm↗
PubMed1997

Intracytoplasmic sperm injection pregnancy with fetal trisomy 9p resulting from a balanced paternal translocation.

Infertile men who carry a chromosomal translocation can be successfully treated with intracytoplasmic sperm injection (ICSI). However, such treatment carries a risk that a pregnancy with an abnormal karyotype will be induced. While in all previously published cases the outcome was favourable, we here report the first instance of a parental reciprocal translocation leading to a chromosomally unbalanced ICSI pregnancy. The fetus, one of a pair of dizygotic twins, was found to have trisomy for the short arm of chromosome 9. The parents opted for selective abortion of the affected twin.

Amniocentesis↗
PubMed1997

The molecular genetics of male infertility.

The important role of genetic abnormalities in the causation of human male infertility is increasingly recognized. While much remains to be learned in this fast moving field, considerable progress has been achieved over the past years both in the clinical delineation of genetic forms of male infertility and in the characterization of the responsible genes and their mutations. We review the current state of knowledge on monogenic disorders where male infertility is a major and regular feature. Clinical and molecular details are given on a total of seventeen such entities. We restrict our survey to disorders that may actually come to the clinical attention of the reproductive medicine specialist.

Abnormalities, Multiple↗
PubMed1997

Genetic counselling for infertile male patients.

A substantial part of the male infertility caseload has a genetic basis. To identify a genetic abnormality in an infertile man is not only important for the patient himself and his offspring, but also for an optimized clinical case management. Laboratory studies (karyotyping, DNA analysis) are often required, but the single most effective diagnostic technique in clinical genetics is taking a meticulous family history. In selected cases a dysmorphological physical examination may be required to recognize a syndromal disorder. The genetic examination may sometimes establish a previously unrecognized diagnosis, and this informs the andrologist about possible risks of an active infertility treatment. However, genetic testing combined with counselling is, above all, intended to be of benefit to the counsellee himself. He should i) be provided with all factual genetic information relevant to his medical situation, and ii) be enabled to reach an informed decision about reproductive goals and strategies, genetic risk taking, and prenatal diagnosis if applicable.

Cytodiagnosis↗
PubMed1996

Geographic distribution and origin of CFTR mutations in Germany.

The geographic distribution and origin of CFTR mutations in Germany was evaluated in 658 three-generation families with cystic fibrosis (CF). Fifty different mutations were detected on 1305 parental CF chromosomes from 22 European countries and overseas. The major mutation. delta F508 was identified on 71.5% of all CF chromosomes, followed by R553X (1.8%), N1303K (1.3%), G542X (1.1%), G551D (0.8%) and R347P (0.8%). According to the grandparents' birthplace, 74% of CF chromosomes had their origin in Germany; the delta F508 percentage was 77%, 75%, 70% and 62% in northern, southern, western and eastern Germany, respectively. Ten or more mutant alleles in the investigated CF gene pool originated from Austria, the Czech Republic, Poland, Russia, Turkey and the Ukraine. This widespread geographic origin of CFTR mutations in today's Germany reflects the many demographic changes and migrations in Central Europe during the 20th century.

Cystic Fibrosis↗
PubMed1996

Prevalence of alpha-thalassemias in northern Thailand.

The population of northern Thailand has one of the highest frequencies of alpha-thalassemia in the world. However, the available distributional data are controversial. In addition to deletional types of alpha-thalassemia Hb, type Constant Spring should also be taken into consideration in alpha-thalassemia population studies, because it causes clinical alpha-thalassemia in the homozygous state or when present with both alpha-globin genes deleted in trans. We have examined a sample of 215 healthy subjects from four rural districts of Chiang Mai province. Out of these, 77 exhibited anomalies of the alpha-globin genes (alpha alpha/-alpha 3.7 in 36; -alpha 3.7/-alpha 3.7 in 3; -SEA in 30; alpha alpha/alpha CS alpha in 5; alpha alpha alpha anti 3.7 in 3). Therefore, no fewer than 2% of the children in northern Thailand are expected to be born with HbH disease or thalassemic hydrops fetalis. The considerable public health problem of hemoglobinopaties and the increasing acceptance of family planning necessitates facilities for the pre- and postnatal diagnosis of these disorders at the DNA level.

Adolescent↗