Using Bacterial Artificial Chromosomes in Leukemia Research: The Experience at the University Cytogenetics Laboratory in Brest, France

The development of the bacterial artificial chromosome (BAC) system was driven in part by the human genome project in order to construct genomic DNA libraries and physical maps for genomic sequencing. The availability of BAC clones has become a valuable tool for identifying cancer genes. We report here our experience in identifying genes located at breakpoints of chromosomal rearrangements and in defining the size and boundaries of deletions in hematological diseases. The methodology used in our laboratory consists of a three-step approach using conventional cytogenetics followed by FISH with commercial probes, then BAC clones. One limitation to the BAC system is that it can only accommodate inserts of up to 300 kb. As a consequence, analyzing the extent of deletions requires a large amount of material. Array comparative genomic hybridization (array-CGH) using a BAC/PAC system can be an alternative. However, this technique has limitations also, and it cannot be used to identify candidate genes at breakpoints of chromosomal rearrangements such as translocations, insertions, and inversions

Hygroma kystique de cou. Diagnostic anténatal, facteurs pronostiques, conduite à tenir. A propos de 42 cas

[Cystic hygroma of the neck. Antenatal diagnosis, prognostic factors, management. 42 cases] The authors report a series of 42 cases of cystic hygroma of the fetal neck diagnosed antenatally. Cystic hygroma is one of the signs suggestive of chromosomal or congenital abnormalities that occur very early and are very specific. A diagnosis can be made from the ninth week of amenorrhoea onwards by vaginal ultrasound. 73% of the karyotypes that were obtained were abnormal. The large majority (54% = have Turner's Syndrome, but there are some of the karyotypes that are normal. Our figures correspond with those in the literature. Several factors were analysed to show the influence of this pathology on the prognosis which is overall awful (only 11.5% of infants were born alive an only 7.5% survived). Factors for a good prognosis would be a normal karyotype and the spontaneous resolution of cystic hygroma in the second trimester of the pregnancy. Hydrops is a factor of poor prognosis and it occurs in 60% of cases of cystic hygroma but unfortunately 30% of cases where the karyotype is normal have severe malformations (bone, kidney and digestive tract). The resolution of the cystic hygroma in the second trimester of pregnancy does not exclude an abnormal karyotype or a severe congenital malformation associated with the condition. As cases do recur in the same family there is an indication that a suspicion that the condition can be an autosomic, recessive or even dominant condition. The authors advise that the diagnosis should be made early and thoroughly in order to carry out chorionic villus sampling to determine the karyotype early before the very important sign for abnormality disappears as it may

Difficult diagnosis and management of an heterokaryotypic monochorionic twin pregnancy with discordant fetal sex and 45,X/47,XYY karyotypes.

International audienceWe report twins for whom ultrasound examinations revealed a Turner syndrome in the female fetus and a normal male fetus. A selective pregnancy termination was decided on the female fetus with hydrops. The death of both twins called in question the chorionic diagnosis. Amniotic fluid cytogenetic analysis revealed a 45,X karyotype in the female twin and a 47,XYY karyotype in the male twin. Molecular cytogenetic analysis on genital and renal cells showed different levels of 45,X/47,XYY mosaicism in both twins; molecular analysis on the amniocytes showed monozygosity. Monozygotic twins with discordant sex are very rare. This study showed the difficult diagnosis and management of a monochorionic twin pregnancy with discordant fetal sex