Transition from normal to premutated alleles in fragile X syndrome results from a multistep process.

In fragile X syndrome, the most common cause of inherited mental retardation, phenotypic expression has been linked to a region containing a repetitive sequence, (CGG)n, that appears to lengthen dramatically in fragile X patients and to show length variation in normal individuals. In order to investigate possible mechanisms responsible for further expansion of CGG in the normal population, we selected 31 normal unrelated X chromosomes carrying either the high-risk DX204-AC155 or DX196-AC151 haplotypes, as defined by the flanking microsatellites, DXS548 and FRAXAC2. Nearly 100% of CGGs with more than 35 repeats were found on DX204-AC155 haplotypes, with a mean length significantly higher and much more variable than in normal individuals carrying other haplotypes including the high-risk haplotype DX196-AC151. These findings suggest that the transition from the normal to the abnormal range occurs by a multistep process, a primary event, such as unequal crossing-over, leading to increased size and moderate instability of the repeat, and from which DNA polymerase slippage could lead to recurrent premutations. Our results also suggest that the upper limit of the normal range is roughly 35 repeats in the fragile X gene. The 36-54 repeats range would define an intermediate allele only observed, up to now, in DX204-AC155 fragile X chromosomes.

[Comparative study of the lipid composition of seminal fluid and ovulatory peritoneal fluid in humans]. / Etude comparative de la composition lipidique du liquide séminal et du liquide péritonéal ovulatoire dans l'espèce humaine.

Sperm capacitation is accompanied by changes in the lipid composition of the sperm membrane. The purpose of this study is to compare the lipid composition of the semen with that of peritoneal fluid. These two media have opposite effects on sperm capacitation. Cholesterol, triglyceride and phospholipids were measured in seminal fluid (15 specimens) obtained by sperm centrifugation immediately after liquefaction and in the peritoneal fluid at ovulation (15 specimens) obtained through transvaginal puncture. The lipid composition of these two media is different from that of serum. Seminal fluid is characterized by a high level of phospholipids, 14.79 +/- 3.67 g/l as against 0.53 +/- 0.12 g/l in peritoneal fluid. The level of cholesterol is identical in the two media. The cholesterol/phospholipid ratio is therefore lower in seminal fluid than in peritoneal fluid (0.022/0.79). Lecithins are raised in peritoneal fluid as are sphingomyelins and the phosphatidylethanolamines, which are the most important phospholipids in seminal fluid. It therefore can be postulated that the cholesterol/phospholipid ratio, which is low in seminal fluid, and its richness in sphingomyelin brings about stabilization of the membrane cover which corresponds to a decapacitated state, whereas the cholesterol/phospholipid ratio, which is higher in peritoneal fluid, makes for greater fluidity, and this corresponds to the state of capacitation. These preliminary results obtained from human material do not in any way contradict those obtained from animal studies.