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Biomedical subjects

P Kroisel

Publications and source records attributed to P Kroisel.

7 recordsLinked to original sources
PubMed2000

Imprinting centre deletions in two PWS families: implications for diagnostic testing and genetic counseling.

Prader-Willi syndrome (PWS) is a complex genetic syndrome involving imprinted genes on chromosome 15. It is usually sporadic, and very few affected siblings have been described. Here, we report the clinical and molecular findings in two families with a microdeletion affecting the chromosome 15 imprinting centre (IC). Carrier males have a 50% risk of having children with an imprinting defect leading to PWS, and in one of the two families, a father has two affected daughters. In the other family, diagnostic testing was confounded by the presence of a neutral microdeletion close to the IC. The silent transmission of PWS IC deletions through the female germline and the occurrence of neutral microdeletions close to the IC can impose considerable problems on diagnostic testing and genetic counselling in affected families.

Alleles↗
PubMed2000

Familial mental retardation syndrome ATR-16 due to an inherited cryptic subtelomeric translocation, t(3;16)(q29;p13.3).

In the search for genetic causes of mental retardation, we have studied a five-generation family that includes 10 individuals in generations IV and V who are affected with mild-to-moderate mental retardation and mild, nonspecific dysmorphic features. The disease is inherited in a seemingly autosomal dominant fashion with reduced penetrance. The pedigree is unusual because of (1) its size and (2) the fact that individuals with the disease appear only in the last two generations, which is suggestive of anticipation. Standard clinical and laboratory screening protocols and extended cytogenetic analysis, including the use of high-resolution karyotyping and multiplex FISH (M-FISH), could not reveal the cause of the mental retardation. Therefore, a whole-genome scan was performed, by linkage analysis, with microsatellite markers. The phenotype was linked to chromosome 16p13.3, and, unexpectedly, a deletion of a part of 16pter was demonstrated in patients, similar to the deletion observed in patients with ATR-16 syndrome. Subsequent FISH analysis demonstrated that patients inherited a duplication of terminal 3q in addition to the deletion of 16p. FISH analysis of obligate carriers revealed that a balanced translocation between the terminal parts of 16p and 3q segregated in this family. This case reinforces the role of cryptic (cytogenetically invisible) subtelomeric translocations in mental retardation, which is estimated by others to be implicated in 5%-10% of cases.

Abnormalities, Multiple↗
PubMed1999

Rapid prenatal diagnosis of aneuploidy by quantitative fluorescent PCR on fetal samples from mothers at high risk for chromosome disorders.

We report the results of a prospective study using quantitative fluorescent polymerase chain reaction (QF-PCR) and small tandem repeat markers (STR) for the rapid prenatal detection of aneuploidies in a group of pregnant women at increased risk of having fetuses with numerical chromosome disorders. Amniotic fluid samples (n = 52) were collected from mothers undergoing prenatal invasive testing for fetal abnormalities on ultrasonographic examination or abnormal maternal serum aneuploidy screening results. All samples were tested by cytogenetic analysis, but rapid diagnoses of aneuploidies were offered and performed using QF-PCR analysis with several STRs specific for chromosomes 21, 18, 13 and X. All cases with numerical chromosome aberrations involving chromosomes 21, 18 and 13 (n = 8) were correctly diagnosed. Three gonosomal aneuplodies (one 47,XXY and two 45,X) were not detected because they were uninformative for the X markers. Another sample with a deletion (46,XX,7q-), that the present assay was not designed to detect, was not identified. One sample was heavily contaminated with maternal blood and the results of the QF-PCR assays were uninformative. The remaining samples from normal fetuses provided QF-PCR patterns disomic for chromosomes 21, 18, 13 and X. Our study demonstrates that QF-PCR is a rapid method for the detection of common numerical chromosome disorders and it may play an important role in prenatal diagnosis for women at high risk for fetal aneuploidy.

Amniocentesis↗
PubMed1994

TXK, a novel human tyrosine kinase expressed in T cells shares sequence identity with Tec family kinases and maps to 4p12.

A gene for a novel, putative cytoplasmic tyrosine kinase, TXK has been isolated from a human peripheral blood cDNA library. The complete nucleotide sequence of the cDNA indicates that it is related most closely to EMT, a tyrosine kinase of T cells and to the B-cell tyrosine kinase Btk, which is mutated in X-linked agammaglobulinemia (XLA) in humans and X-linked immunodeficiency disease (XID) in mouse. TXK, like BTK, is a member of the Tec sub-family of Src-type (non-receptor) tyrosine kinases. Like similar Tec sub-family members, and unlike the other Src kinases, TXK lacks both the N-terminal myristylation signal and the C-terminal regulatory tyrosine. TXK expression is detected primarily in T cells and some myeloid cell lines but not in a number of other cell types. TXK shares 60% amino acid homology with EMT and 57% with BTK over the SH3, SH2 (Src-homology) and catalytic domains but unlike BTK, EMT and tec, it lacks Gap 1 homology and steroid hormone receptor homology in the N-terminal region. Genomic clones containing TXK have been isolated and hybridize to chromosome position 4p12.

Amino Acid Sequence↗
PubMed1984

Cold air challenge of airway hyperreactivity in children: practical application and theoretical aspects.

In 23 children with asthma and 18 healthy controls, cold air challenge ( CACh ) was done twice during the same half day, and in the asthmatics a third time together with a histamine challenge (HCh) 2 wk later. Pulmonary functions were tested before and after each challenge. No overlapping of individual responses to CACh in seven forced expiratory flow tests proved the power of discrimination of this technique in children. The limits of "normal" reactions ranged from minus 9% for larger airway-related to 26% for smaller airway-related flows. Short-term reproducibility of induced changes, in percentage of baseline, was excellent (r = 0.815-0.954); in percentage of predicted postchallenge abnormality it was even better (r = 0.926-0.975). The response in small airway-related flow rates (-43.1 +/- 12.8 to -51.9 +/- 16.8% of baseline) was much larger than in others (-27.6 +/- 14.6 to -32.1 +/- 17.3% of baseline). This, the different baseline-to-response correlations in various measurements, and the divergent dose response to colder versus less cold air in large (60.7 +/- 21.9 versus 65.4 +/- 21.5% predicted, postchallenge values) and small airway-related tests (28.9 +/- 18.7 versus 29.5 +/- 15.1% predicted, postchallenge values) in asthmatic children suggest a predetermined, small airway-related limitation of individual reactivity, which is independent of the baseline situation. All asthmatics responded positively to HCh but quantitative results of the two methods did not correlate. Responses to CACh also better characterized the clinical severity of asthma than those of HCh.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗