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Wendy P Robinson

Publications and source records attributed to Wendy P Robinson.

10 recordsLinked to original sources
PubMed2025

Placental CCR5 polymorphisms in relation to fetal growth.

The placenta mediates fetal growth, and its development and function are influenced by immune interactions at the maternal-fetal interface. The cysteine-cysteine chemotactic cytokine receptor type 5 (CCR5) gene codes for a pro-inflammatory protein receptor expressed in the placenta on syncytiotrophoblasts and Hofbauer cells. Associations of the placental-fetal genotype at CCR5 and birth outcomes have not been examined. Furthermore, influence of CCR5 polymorphisms on nearby DNA methylation in the placenta and in the context of infection is understudied. We assessed two functional polymorphisms in CCR5, a 32 base pair deletion (Δ32) in the open reading frame and an A/G promoter point mutation (rs1799987) in EPIC (n = 233) a cohort consisting of complicated and uncomplicated pregnancies ascertained in Vancouver BC and found that the variant alleles were associated with birth weight (p = 0.007 and p = 0.01 respectively). We validated the association of rs1799987 with birthweight (p = 0.003) in the published NICHD dataset of normative term births (n = 286). These variant associations were, however, not present in CARMA-Preg (n = 200) a cohort enriched for HIV-exposure. Interestingly, we found rs1799987 was associated with altered DNA methylation (DNAme) at multiple CpGs spanning over 275 kb, overlapping both the CCR2 and CCR5 genes. DNAme in this region was, however, not associated with birthweight. Further investigations are needed to validate the association of CCR5 variants with fetal growth. Such studies must consider the population structure and demographics, as well as the large haplotype blocks spanning this region, which make it difficult to assign a causal relationship to specific variants.

Humans↗
PubMed2006

Origin and outcome of pregnancies affected by androgenetic/biparental chimerism.

BACKGROUND: Androgenetic diploid cells confined to the placenta have recently been reported in several cases of normally developed fetuses in association with placental mesenchymal dysplasia (PMD). METHODS AND RESULTS: We investigated two singleton, mildly growth-restricted, female pregnancies ascertained on the basis of PMD. One case had liver hemangiomas and both infants had multiple skin hemangiomas. Post-natal development was normal. Molecular marker analysis confirmed the diagnosis of androgenetic and normal mixed cell populations in the placenta. Both cases derived from a single maternal genome (M1) and two distinct paternal genomes (P1 and P2). In one case, the androgenetic cell population contained both paternal genomes (P1P2), with one shared in common with the biparental (M1P1) population. In the second case, the androgenetic lineage showed complete homozygosity (P2P2) for a paternal genome not common to the biparental cell population. CONCLUSION: These new PMD cases help to define the range of possible clinical presentations of androgenetic/biparental mosaicism or chimerism. Placentas with androgenetic/biparental chimeric cell populations may derive from a single tri-pronuclear (3PN) zygote in which one or more parental genomes are not equally apportioned to the daughter cells in the first cell division.

Alleles↗
PubMed2006

Postnatal follow-up of prenatally diagnosed trisomy 16 mosaicism.

OBJECTIVE: To determine the long-term outcome of pregnancies prenatally diagnosed with trisomy 16 and identify variables associated with the outcome. METHODS: We reviewed all published and our unpublished data from trisomy 16 pregnancies for which outcomes were available for children of greater than 1 year of age. RESULTS: Nineteen cases were diagnosed with trisomy 16 on chorionic villus sampling (CVS) and 17 cases at amniocentesis. Age at last follow-up ranges from 1 to 13 years. Among the CVS group, four out of five patients, with a birth weight and/or length below -2 SD and postnatal growth information, showed catch-up growth (80%). Among the amniotic fluid (AF) group, the birth weight was available in 13 cases. Eleven of the 13 cases had a birth weight less than -2 SD. In eight cases, the length was also below -2 SD (length data unavailable in one case). Nine out of ten cases (90%) and seven out of eight (87.5%) showed catch-up growth for weight and length, respectively. In terms of development, no cases of CVS mosaicism had global developmental delay. One child had a history of delay in speech development. Among the AF-detected cases, 4/17 cases had global developmental delay. All four children with global developmental delay had more than one major malformation compared to 6 out of 32 children in the group with normal development (p = 0.004). The finding of uniparental disomy (UPD) was not associated with developmental delay. CONCLUSIONS: The majority of prenatally diagnosed trisomy 16 mosaic cases have a good postnatal outcome. However, the finding of mosaicism on AF and the presence of major congenital anomalies are associated with an increased risk of developmental delay.

Amniocentesis↗
PubMed2005

FMR1 repeat sizes in the gray zone and high end of the normal range are associated with premature ovarian failure.

Premature ovarian failure (POF) is the occurrence of menopause before the age of 40 and affects 1% of the female population. Whereas the etiology of POF is largely unexplained, FMR1 premutation carriers are known to be at increased risk of POF compared with the general population. The FMR1 premutation alleles have 55-200 copies of a CGG repeat in the 5' untranslated region of the FMR1 gene. However, functional effects on gene expression may occur even for repeat sizes in what has been considered the "normal" range. To evaluate the role of the FMR1 repeat in POF, repeat sizes were examined in 53 women with idiopathic POF, 161 control women from the general population, and 21 women with proven fertility at an advanced maternal age. A significant increase in the number of FMR1 alleles between and including 35 and 54 CGG repeats was found in the POF patient population; 15 of 106 (14.2%) POF alleles were between and including 35 and 54 repeats, whereas only 21 of 322 (6.5%) alleles in the general population (P=0.02) and 2 of 42 (4.8%) alleles from women with proven late fertility (P=0.09) were of this size (P=0.01 versus combined controls). The effect was also significant for comparisons of genotype repeat size (repeat size weighted by the relative activity of the two FMR1 alleles) and biallelic mean (average size of the two alleles). These results are clinically relevant and suggest that the FMR1 gene plays a more significant role in the incidence of POF than has previously been thought.

Female↗
PubMed2003

Prenatally detected trisomy 4 and 6 mosaicism--cytogenetic results and clinical phenotype.

We report on a live-born male with 46,XY/47,XY+4/47,XY,+6 mosaicism. Trisomy 4 mosaicism was detected by karyotyping chorionic villus samples (CVS) and was confirmed by the analysis of 16 metaphases obtained from cultured amniotic fluid cells. Eight metaphases were normal (46,XY), two had trisomy 4 (47,XY,+4), and two had trisomy 6 (47,XY,+6). Two postnatal chromosomal analyses of blood lymphocytes at birth and at the age of one week were normal. Chromosomal analysis of cultured skin fibroblasts from the right inguinal region at the age of 12 months revealed trisomy 4 (47,XY,+4) in 49 metaphases, trisomy 6 (47,XY,+6) in 2 metaphases, and a normal karyotype (46,XY) in 49 cells of the 100 analyzed metaphases, respectively. The main clinical findings consist of prenatal growth retardation, hypoplasia of the right side of the face, a dysplastic and posteriorly rotated right ear, a high vaulted palate, retrognathia, aplasia of the right thumb, hypoplasia of the fingernails, a deep sacral dimple, and patchy skin hypopigmentation of the right leg. When last seen at the age of 14 months, his development was nearly normal. Five patients with trisomy 4 mosaicism have been reported previously, but none with an additional trisomy 6 mosaicism.

Abnormalities, Multiple↗
PubMed2002

Origin of amnion and implications for evaluation of the fetal genotype in cases of mosaicism.

OBJECTIVE: To investigate presence of trisomy in amniotic epithelium (uncultured amnion) and mesenchyme (cultured amnion) from mosaic cases to understand the origins of these tissues and their relationship to pregnancy outcome. METHODS: Polymerase chain reaction (PCR) of microsatellite loci was used to determine the presence of trisomy (of meiotic origin only) in amnion samples from 33 placentas previously ascertained because of a prenatal diagnosis of trisomy mosaicism that was predominantly confined to the placental tissues. RESULTS: In 16 (48%) of 33 cases, trisomy was confirmed to be present by molecular analysis of uncultured amnion. In contrast, cytogenetic analysis of cultured amnion showed trisomy in only 2 of 20 informative cases. The molecular detection of trisomy in amnion was strongly associated with poor pregnancy outcome (intrauterine growth restriction, fetal anomalies and/or intrauterine/neonatal death) even when analysis was limited to cases negative for the trisomy on amniotic fluid (N = 22, p = 0.0005). CONCLUSIONS: We infer that amniotic mesenchyme (usually diploid) derives from early embryonic mesoderm of the primitive streak and not from the hypoblast as is commonly cited. Trisomy in amniotic epithelium suggests that high numbers of abnormal cells were present in the epiblast, and this correlates with poor outcome even when the subsequently derived fetus and amniotic mesenchyme appear to carry only diploid cells.

Abnormalities, Multiple↗
PubMed2002

Dispermy--origin of diandric triploidy: brief communication.

Triploidy may arise from either digynic or diandric fertilizations. Errors in the second meiotic division account for most digynic triploidy while most studies have found that approximately 2/3 of diandric triploids arise as the result of dispermy and 1/3 as the result of meiotic errors giving rise to diploid sperm. Using molecular markers very close to the centromere, all 14 cases of diandric triploidy were shown to be the result of dispermy with no evidence to support a meiotic error as the origin of diandric triploids.

Centromere↗