Germline mosaicism complicates molecular diagnosis of Lesch–Nyhan syndrome

A healthy female with a brother suffering from Lesch–Nyhan syndrome was assigned a carrier status on the basis of haplotype analysis employing flanking and intragenic polymorphic markers of the HPRT gene. Her mother has been confirmed as a definite carrier by cell growth selection studies in cultured fibroblasts. In our proposita's first pregnancy, a male fetus was identified carrying the risk allele. Afterwards, the underlying novel mutation A161E (GCA→GAA at position c482) could be identified in the affected brother and in the heterozygous mother but not in the DNA of the pregnant sister and fetus. The fetus was also confirmed to be normal by uptake of 14C-hypoxanthine in cultured amniotic cells. To test the discrepancy, the investigation was extended by recruiting additional family members. The data obtained showed that the mother had passed her risk haplotype to the affected son as well as to her mutation-carrying and non–mutation-carrying daughters. This provides the first evidence of concomitant somatic and germline mosaicism in Lesch–Nyhan syndrome. The study has a bearing on genetic counselling and cautions against the reliability of only using indirect genetic diagnosis even with intragenic markers. Copyright © 2004 John Wiley & Sons, Ltd.     

柞蚕多角体病毒的纯化和鉴定

对柞蚕多角体病毒(ApNPV)的多角体颗粒进行了分离和纯化,并在显微镜下进行了形态观察．提取和纯化了柞蚕多角体病毒的基因组DNA,对DNA进行了部分限制性内切酶图谱鉴定．结果表明,在ApNPV基因组中只含少量的EcoRI位点,与家蚕核型多角体病毒差别很大,并提示这两种病毒的复制机制可能不同．图3参5。     

Karyotype,phenotype and parental origin in 19 cases of triploidy

The parental origin of triploidy in 19 cases was examined by inheritance of DNA microsatellites and by methylation patterns of SNRPN or PW71 (where parents' blood was unavailable). The fetal and placental morphology on these cases was reviewed. The phenotype of the fetuses with non-mosaic triploidy was assessed in relation to the two types described by McFadden and Kalousek. Of the diandric fetuses three of the six showed mild-to-moderate symmetrical growth retardation and the other three had growth characteristics in accordance with their gestational ages. This study would suggest the fetal triploid ‘Type 1’ definition be modified to ‘well grown to moderate symmetrical IUGR’ to allow for such variation. In the digynic fetuses (McFadden/Kalousek Type 2) there were poor growth characteristics with IUGR being more severe and asymmetrical. The diandric fetuses were as common as digynic fetuses in this series. The ratio of diandric to digynic specimens was 11:8 but if only fetal specimens (not embryos or mosaic children) were included the ratio was 6:5. Many diandric conceptions end as partial moles but later in gestation diandric fetuses may be well grown. It is proposed that there may be a survival barrier for diandric fetuses early in gestation (possibly based on the proportion of vascularised placental villi), although once this is passed the diandric fetuses are comparatively more viable and better grown than digynic fetuses. In the XXY triploid fetuses, 5/6 had hypoplastic or ambiguous external genitalia (two were recorded as of female phenotype) as has been reported previously. In these, the gonadal histology was testicular in all the diandrics but in the single digynic XXY case, sex reversal was complete with normal uterus and Fallopian tubes and the gonads were histologically ovaries. Two triploid/diploid mosaics were proven to be due to digyny. The probable cause is delayed incorporation of the second polar body into a blastomere and there was evidence of identical alleles from the same sperm being present in both diploid and triploid cells. In one of these triploid/diploid mosaics in which there was a termination of pregnancy (TOP) after prenatal karyotyping the diploid cell line had trisomy 16 which was not evident in the triploid line. This trisomy was probably of post-zygotic origin and we suggest the fetus was rescued by the prominence of the triploid line. Copyright © 2001 John Wiley & Sons, Ltd.