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Biomedical subjects

I H Pawlowitzki

Publications and source records attributed to I H Pawlowitzki.

At least 19 recordsLinked to original sources
PubMed1997

Molecular basis of choroideremia (CHM): mutations involving the Rab escort protein-1 (REP-1) gene.

Choroideremia (CHM) is an X-linked recessive eye disease that results from mutations involving the Rab escort protein-1 (REP-1) gene. In 18 patients deletions of different sizes have been found. Two females suffering from CHM were reported to have translocations that disrupt the REP-1 gene. In 22 patients, small mutations have been identified. Interestingly, these are all nonsense, frameshift or splice-site mutations; with one possible exception, missense mutations have not been found. This comprises all the known mutations in the disease.

Adaptor Proteins, Signal Transducing↗
PubMed1994

Mutation spectrum in the CHM gene of Danish and Swedish choroideremia patients.

The recent isolation of the complete open reading frame of the choroideremia (CHM) gene and the characterization of the exon-intron boundaries has paved the way to mutation detection in patients with classical choroideremia. We have performed mutation screening in patients from 15 Danish and Swedish families by using Southern blot hybridization and the polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) technique. Causative mutations in the CHM gene were detected in at least 12 families, indicating that a substantial part of the mutations can be identified by this approach. In four of these families deletions of different sizes were found. Thus, in one patient, the deletion resulted in the absence of only one exon, while in another the deletion comprised the entire CHM gene. Mapping of the deletion endpoints in these four patients and in another 11 male patients with sizeable deletions enabled us to construct a very detailed map of intervals 2 and 3 of Xq21. In the remaining 11 Danish and Swedish families at least 8 causative mutations were found by PCR-SSCP analysis and direct sequencing. Interestingly, all CHM gene mutations detected thus far in choroideremia patients give rise to the introduction of a premature stop codon.

Adaptor Proteins, Signal Transducing↗
PubMed1992

Prenatal exclusion of choroideremia.

We performed prenatal testing to predict the inheritance of choroideremia (CHM) using a linked polymorphic DNA marker, DXS95. DNA analysis of chorionic villi at the 12th week of pregnancy indicated that the allele at risk had not been passed from the heterozygous mother to the fetus. This prenatal exclusion of choroideremia was confirmed by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) analysis.

Adult↗
PubMed1992

Detection and characterization of point mutations in the choroideremia candidate gene by PCR-SSCP analysis and direct DNA sequencing.

By making use of positional cloning strategies we recently isolated a candidate gene for choroideremia (CHM), which is transcribed in retina, choroid, and/or retinal pigment epithelium. The gene contains an open reading frame that is structurally altered in 10 CHM patients with sizable deletions and in a female patient with a balanced translocation involving the Xq21 band. Employing PCR-SSCP analysis and direct DNA sequencing we have now detected and characterized different point mutations in five patients with CHM. Each of these mutations introduces a termination codon into the open reading frame of the CHM candidate gene, thereby predicting a distinct truncated protein product. Together these findings provide convincing evidence for the candidate gene being identical with the choroideremia gene.

Amino Acid Sequence↗
PubMed1990

Cloning of the breakpoints of a deletion associated with choroidermia.

In order to characterize a previously described submicroscopic deletion encompassing (part of) the choroideremia (tapetochoroidal dystrophy: TCD) gene, we have cloned a 10.5-kb EcoRI fragment from the patient's DNA; this fragment carries the junction between both deletion endpoints ("junction fragment"). The distal portion of this fragment defines a new marker within, or just distal to, the TCD gene. This marker has been employed to confirm the diagnosis in several affected family members, and to rule out carriership in a female at risk with conspicuous clinical signs.

Blotting, Southern↗
PubMed1989

Validity of cytogenetic analyses from trophoblast tissue throughout gestation.

Cytogenetic findings in the Münster Chorionic Villi Sampling (CVS) program are presented after 1,184 first trimester transcervical samplings and 131 second and third trimester placentacenteses. In the first trimester series the abnormality rate is low (2.4%) in patients with only an age-dependent aneuploidy risk. In this group terminations were performed in only 1.6% because of aneuploidy. True mosaicism was found more frequently after CVS, and the risk of maternal cell contamination seems higher as compared to amniocentesis. There are no obvious differences in the overall rate of diagnostic errors after both procedures, when metaphases after direct preparation and chorionic cell cultures are analysed and doubtful findings such as mosaicism are adequately followed up by amniocentesis. The cytogenetic techniques also offer a very rapid approach to karyotyping in the second and third trimester. We found a high rate of aneuploidy (15%) when placentacentesis was performed after sonographic diagnosis of fetal abnormalities. We conclude that cytogenetic analysis from trophoblast tissue is an accurate diagnostic tool applicable from first to third trimester of pregnancy.

Amniocentesis↗
PubMed1989

[Immunotherapy following habitual abortion in paternal chromosome translocation].

In a 41-year-old VII-gravida, I-para, the husband's reciprocal translocation of the chromosomes 1 and 18 as well as a partial identity of the marital partner in the HLA-system may have been the underlying causes for five abortions. In the 7th pregnancy, a prenatal chromosome analysis was performed as well as an immunotherapy with paternal lymphocytes, when uterine bleeding occurred. After termination of bleeding, the pregnancy continued without any complication. Our case report demonstrates the importance of an extensive search for causes leading to recurrent abortions not only with regard to diagnosis but also with regard to therapy in pregnancy.

Abortion, Habitual↗
PubMed1988

Rapid karyotyping for prenatal diagnosis in the second and third trimesters of pregnancy.

Direct chromosome preparations were performed on placental villi obtained by ultrasound-guided needle aspiration between 18 and 37 weeks of pregnancy in 53 patients. The sampling yielded a sufficient amount of tissue with a maximum of two, and in most cases one, insertions. Placental biopsy is easily performed in cases of severe oligohydrammnios, where fetal blood sampling is usually more difficult. Direct karyotyping of placental villi is faster than chromosome analysis from fetal blood or application of the pipette method on amniotic fluid cells, and currently represents the most rapid approach to prenatal diagnosis of chromosomal abnormalities from the first to the third trimester of pregnancy.

Biopsy, Needle↗
PubMed1988

Feto-maternal transfusion after chorionic villus sampling. Evaluation by maternal serum alphafetoprotein measurement.

The alphafetoprotein (AFP) concentration in maternal serum was determined before and after chorionic villus sampling (CVS). A significant increase of 20% or more in the pre-CVS level was noted immediately after sampling in 59% of 837 pregnancies indicating some degree of feto-maternal haemorrhage. The increase in the AFP concentration in maternal serum was correlated with the weight of the tissue sample but not with the number of sampling attempts. A correlation of AFP increase and frequency of spontaneous abortions following CVS was suggested only in the group with an AFP increase of more than 100% or with a continuing rise in the first hour following CVS. CVS in early pregnancy obviously did not interfere with maternal serum AFP screening for neural tube defects in the second trimester. Although AFP measurement before and after CVS seems to have no immediate diagnostic application, in the research phase of CVS it may help to identify those procedures that are the least traumatic.

Abortion, Spontaneous↗
PubMed1988

A sex cord stromal tumour in a woman with XO/XX/XXX-mosaicism.

We describe a postmenopausal woman with 45,XO/46,XX/47,XXX mosaicism who presented with a Sertoli-Leydig cell tumour and a past history of habitual abortion. The cytogenetic finding is discussed in relation to the etiology of the tumour and of the recurrent abortions.

Female↗
PubMed1988

[Fatal re-infarct in pregnancy].

We report on the third pregnancy of a 41-year-old patient with familial hypercholesterolemia. After preceding angina pectoris symptoms she had her first myocardial infarction at an age of 37. Thereafter she had no complaints under medicinal and dietary treatment. During her third pregnancy angina pectoris symptoms occurred again and finally a myocardial re-infarction caused her death. Our case report shows, that the hemodynamic alterations in pregnancy can aggravate the patient's situation even in prepartally uncomplicated coronary diseases.

Adult↗
PubMed1987

Estimating frequency of Kallmann syndrome among hypogonadic and among anosmic patients.

The frequency of Kallmann syndrome (hypogonadotropic hypogonadism and anosmia, HHA) was estimated in patients presenting with hypogonadism and patients with anosmia. Of 791 hypogonadal males 19 had HHA. The frequency of HHA was about 1:25 (n = 8/189) in outpatients questioned about their sense of smell, about 1:50 (n = 11/579) in patients whose blood samples were sent to us for chromosome analysis, and about 1:30 (n = 19/605) in males with hypogonadism and 46,XY chromosomes. The relation of patients with HHA to those with Klinefelter syndrome was 1:10 (n = 19/186). From 24 patients presenting with anosmia we found 1 hitherto undiagnosed case of HHA. The mean age at diagnosis was 24.8 and 24.9 years in our cases and cases from literature, respectively. These data provide evidence that Kallmann syndrome is not infrequent and that most patients remain undiagnosed until the third decade of life. Earlier diagnosis is emphasized by questioning each hypogonadal patient about his sense of smell because therapeutic success seems to be age dependent.

Adolescent↗
PubMed1987

C-band polymorphisms of chromosome 9: quantification by Ce-bands.

C-band polymorphisms of chromosome 1 can be quantified by Ce bands visualized using oblique epi-illumination. In this paper the polymorphic region of chromosome 9, including variants such as 9qh+, inversions, and translocations, was analyzed in a total of 1860 chromosomes from 20 individuals and 8 fetuses. In this sample we found between zero and five Ce bands on 9q and between zero and four Ce bands on 9p with a maximum of five Ce bands per chromosome. On the basis of these observations at least 19 different polymorphic patterns can be expected theoretically, 15 of which were observed in our sample. Among these, five polymorphic Ce-band classes were distinguishable by the method presented. Considering both homologues, 5(2) = 25 quantitatively discernible chromosome 9 pairs may exist.

Chromosome Banding↗
PubMed1987

Three cases of 45,X/46,XYnf mosaicism. Molecular analysis revealed heterogeneity of the nonfluorescent Y chromosome.

Three patients with 45,X/46,XYnf mosaicism were investigated by Southern hybridization using both X- and Y-specific DNA probes. Our patients seem to be hemizygous for the X chromosomal loci tested. Single-copy and low-copy repeated Y chromosomal sequences assigned to the short arm, centromere, and euchromatin of the long arm have been detected in our patients, suggesting the Y chromosomal origin of the marker chromosome both in male and female cases studied. Densitometry of autoradiographs revealed a double dose of Yp-specific fragments of the DXYS1 locus. None of the patients tested showed either the 3.4- or the 2.1-kb Hae III male-specific repeated DNA sequences. It seems likely that the Ynf is a pseudodicentric chromosome with duplication of Yp and euchromatic Yq sequences, the Yq heterochromatin being lost. Our findings indicate structural heterogeneity of the marker chromosome and in addition provide further information on the relative position of DNA sequences detected by DNA probes 50f2, M1A, and pDP105.

Chromosome Banding↗
PubMed1987

Deletion of the DXS165 locus in patients with classical choroideremia.

Using various probes from the Xq21 region which is known to carry the choroideremia (tapetochoroideal dystrophy, TCD) locus, we have screened the DNAs from eight unrelated male choroidermia patients for microdeletions. In two of these patients, but not in any of 45 males tested as controls, lack of hybridization signals with probe plbD5 suggested a deletion encompassing the DXS165 locus and (part of) the TCD gene. Absence of additional clinical features in these patients and the fact that two closely linked, and probably flanking, TCD markers (DXYS1 and DXS72) are not deleted may indicate that the physical distance between the DXS165 locus and the TCD gene is small.

Choroid↗
PubMed1987

An improved darkfield-illuminator for direct surface imaging of chromosomes.

An improved darkfield-illumination system for comfortable and convenient use of oblique incidence epi-illumination is described. The illuminator employs a new means for altering the position of the aperture diaphragm allowing a subtle adjustment of both the direction and the angle of the incident light bundle. The efficacy of this device for surface imaging is demonstrated in human chromosomes. The device permits an improved visualization of subtle Giemsa bands and the detection of sub-bands, which have not yet been described in the International System for Human Cytogenetic Nomenclature-High Resolution Banding.

Cells, Cultured↗