Chimeric genes in acute leukemias

In this thesis the genetic analysis of two types of acute leukemia characterized by translocations will be described. Both translocations generate chimeric genes which are specific for these subtypes of leukemia. The non-random changes that occur at the molecular level can be used in addition to karyotyping to diagnose the presence of tumor cells. The linkage of specific subtypes of acute myeloid leukemia with t(6;9) to a consistent rearrangement involving the ~-gene on chromosome 6 and the g.n-gene on chromosome 9 will be shown (Chapters III.2 and ill.3). This is of clinical importance since a correct diagnosis and subclassification indicates the prognosis of the diaease and helps to choose the right therapy, thereby improving the prognosis for a patient. The second type of acute leukemia that will be discussed is the acute lymphoblastic leukemia associated with the t(9;22). Here, rearrangement of genes results in a chimeric bcr-abl gene on the Philadelphia chromosome. A variant of this chimeric gene was found and analyzed (Chapter II.3). The study of altered genes in leukemia provides us with a multitude of questions conceroing their function and role in the origin of the tumor. However, unusual variants of tumor-specific products may help to solve parts of the mystery of tumor formation

XX male with sex reversal and a de novo 11;22 translocation.

Item does not contain fulltex

Novel EBP gene mutations in Conradi-Hunermann-Happle syndrome.

Contains fulltext : 53137.pdf (publisher's version ) (Closed access)BACKGROUND: Conradi-Hunermann-Happle syndrome [X-linked dominant chondrodysplasia punctata type 2 (CDPX2); MIM no. 302960] is an X-linked dominant disorder of cholesterol metabolism that causes a wide spectrum of skeletal abnormalities and linear ichthyosiform skin lesions. Mosaicism is probably responsible for the variability of the phenotype. OBJECTIVES: To describe new mutations in patients with variable manifestations of the disease. METHODS: We studied three patients with CDPX2. We performed mutation analysis of the EBP (formerly known as CDPX2) gene and gas chromatography-mass spectroscopy on serum of two patients. RESULTS: We found two novel (3G-->T and 419-422delTTCT) and one known mutation in the EBP gene. We demonstrated the presence of increased levels of dehydrocholesterol and 8(9)-cholestenol in the two patients with new mutations, confirming the diagnosis of CDPX2 and strongly suggesting that the mutations are indeed pathogenic. One patient had a very mild phenotype, presenting with linear alopecia and a mild symmetrical epiphyseal dysplasia. X-inactivation studies in peripheral blood of all patients showed skewing in only the most severely affected patient. CONCLUSIONS: The strong phenotypic variability in our patients suggests that there is no clear genotype-phenotype correlation

Des fonctions propres de l'operateur d'Orr-Sommerfeld et de son adjoint dans le cas du domaine semi-infini

Extrait de : Comptes rendus de l'Academie des Sciences Paris. Problemes mathematiques de la mecanique/Mathematical problems in mechanics, Tome 313, Serie 1, p. 817-822, 1991SIGLEAvailable at INIST (FR), Document Supply Service, under shelf-number : 22419, issue : a.1991 n.226 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

Sonographic genital ambiguity in a fetus due to a mosaic 45,X/46,X,idic(Y)(qter-p11.32:p11.32-qter) karyotype

Nowadays, improved ultrasound techniques enable the detection of more subtle congenital abnormalities at an earlier stage of fetal development. Current cytogenetic techniques can characterize a chromosomal abnormality in greater detail. These advancements in both diagnostic possibilities have helped to answer many questions but have also created new issues and dilemmas in counselling. This is illustrated by this case report of a 35-year-old woman, who presented at the end of the second trimester of her first pregnancy. Sonographic examination indicated an abnormal external genital in a male fetus. A differential diagnosis of hypospadia was made. During follow-up, an amniocentesis was performed, and this showed a 45,X/46,X,idic(Y)(qter-p11.32::p11.32-qter) karyotype as the cause of the sonographic findings. Cytogenetic characterization of the isodicentric Y chromosome and pre- and post-natal findings in the child are reported. Cases with a similar karyotype reported in the literature are reviewed. Copyright © 2005 John Wiley & Sons, Ltd