A French collaborative survey of 272 fetuses with 22q11.2 deletion: ultrasound findings, fetal autopsies and pregnancy outcomes.

OBJECTIVE: The 22q11.2 deletion (del22q11.2) is one of the most common microdeletions. We performed a collaborative, retrospective analysis in France of prenatal diagnoses and outcomes of fetuses carrying the del22q11.2. METHODS: A total of 272 fetuses were included. Data on prenatal diagnosis, ultrasound findings, pathological features, outcomes and inheritance were analyzed. RESULTS: The mean time of prenatal diagnosis was 25.6 ± 6 weeks of gestation. Most of the diagnoses (86.8%) were prompted by abnormal ultrasound findings [heart defects (HDs), in 83.8% of cases]. On fetal autopsy, HDs were again the most common disease feature, but thymus, kidney abnormalities and facial dysmorphism were also described. The deletion was inherited in 27% of cases. Termination of pregnancy (TOP) occurred in 68.9% of cases and did not appear to depend on the inheritance status. However, early diagnosis was associated with a higher TOP rate. CONCLUSION: This is the largest cohort of prenatal del22q11.2 diagnoses. As in postnatally diagnosed cases, HDs were the most frequently observed abnormalities. However, thymus and kidney abnormalities and polyhydramnios should also be screened for in the prenatal diagnosis of del22q11.2. Only the time of diagnosis appeared to be strongly associated with the pregnancy outcome: the earlier the diagnosis, the higher the TOP rate.

Molecular cytogenetic characterization of two small chromosome 8 derived supernumerary mosaic markers.

Two small supernumerary mosaic marker chromosomes (SMC) were identified by conventional cytogenetics, one prenatally, the other postnatally. Fluorescence in situ hybridization (FISH) techniques, including 24-color FISH, were applied to identify both SMCs and better characterize their constitution. Patient 1: a 29 year-old man, whose wife had a spontaneous abortion, was found to have a small ring of the pericentromeric region of chromosome 8 (47,XY,+r(8)(p11q11)/46,XY). Patient 2: a 37 year-old woman had amniocentesis. The fetus was found to have a SMC; its presence was confirmed postnatally. Several FISH techniques (24-color, whole chromosome paints, centromeres, telomeres, band 8p22) led to the identification of a small analphoid marker. The marker was an inversion-duplication for part of the short arm of chromosome 8 (47,XY,+inv dup (8)(p23pter)/46,XY). The 24-color FISH allowed us to conclude that both markers originated exclusively from chromosome 8. However, the structure and content of the markers were elucidated using other molecular cytogenetic techniques, showing their complementarity.

French multi-centric study of 2000 amniotic fluid interphase FISH analyses from high-risk pregnancies and review of the literature.

This prospective and multi-centric study confirms the accuracy and the limitations of interphase FISH and shows that any cytogenetics laboratory can perform this technique. With regard to the technical approach, we think that slides must be examined by two investigators, because the scoring may be subjective. The main problem with the AneuVysion kit concerns the alpha satellite probes, and especially the chromosome 18 probe, which is sometimes very difficult to interpret because of the high variability of the size of the spots, and this may lead to false negative and uninformative cases. The best solution would be to replace these probes by locus-specific probes. Concerning clinical management, we offer interphase FISH only in very high-risk pregnancies or/and at late gestational age because of the cost of the test. We think that an aberrant FISH result can be used for a clinical decision when it is associated with a corresponding abnormal ultrasound scan. In other cases, most of the time, we prefer to wait for the standard karyotype.

Fluorescent in-situ hybridization and sequence-tagged sites for delineation of an X:Y translocation in a patient with secondary amenorrhoea.

We describe a phenotypically normal female with secondary amenorrhoea due to a translocation of genetic material involving the long arm of chromosome X (Xq28) and the long arm of chromosome Y (Yq11). We used fluorescent in situ hybridization to localize the breakpoint on the Xq. The Y chromosome breakpoint was identified using polymerase chain reaction (PCR) detection of sequence-tagged sites (STS) specific for interval 5 at Yq11.21. The relationship between this X:Y translocation and premature ovarian failure is discussed.

Progesterone and mifepristone modify principally the responses of circular myometrium to oxytocin in preparturient rats: comparison with responses to acetylcholine and to calcium.

We have recently reported that in the pregnant rat myometrium the synthetic OT/AVP V1 antagonist d(CH2)5[Tyr(Me)2]OVT has similar pA2 values against oxytocin (OT) or arginine vasopressin in longitudinal myometrial strips and against arginine vasopressin in circular myometrial strips. However, the antagonist is inactive against OT in circular strips, suggesting that the receptor involved in the action of OT in circular muscle is distinct from the OT receptor in longitudinal muscle. In this study, models of progesterone-blocked and progesterone + mifepristone-induced rat parturition were designed to check whether progesterone modulated OT responsiveness differentially in the two myometrial layers. Responses to OT were measured in organ bath experiments and compared with responses to acetylcholine and to calcium ions (Ca2+) in depolarized myometrial strips. Compared with control animals at day 21 of pregnancy, maximal responses to OT in longitudinally cut strips from progesterone- or progesterone + mifepristone-treated rats were only marginally affected by steroid treatments. In contrast, progesterone almost totally abolished responses to OT in the circular myometrium, whereas mifepristone treatment restored responses to those seen at spontaneous parturition. In both muscle layers, responses to acetylcholine were unaffected by steroid treatments and those to Ca2+ were decreased by progesterone treatment (however, to a lesser extent than those of OT) and were restored by mifepristone. These results suggest the presence of two populations of OT receptors in the myometrium: a constitutive type of receptor predominent in longitudinal muscle and a progesterone-regulated receptor present in circular muscle.