Dataset Information

18q12.3-q21.1 microdeletion detected in the prenatally alcohol-exposed dizygotic twin with discordant fetal alcohol syndrome phenotype.

ABSTRACT: BACKGROUND:A pair of dizygotic twins discordantly affected by heavy prenatal alcohol exposure (PAE) was reported previously by Riikonen, suggesting the role of genetic risk or protective factors in the etiology of alcohol-induced developmental disorders. Now, we have re-examined these 25-year-old twins and explored genetic origin of the phenotypic discordancy reminiscent with fetal alcohol syndrome (FAS). Furthermore, we explored alterations in DNA methylation profile of imprinting control region at growth-related insulin-like growth factor 2 (IGF2)/H19 locus in twins' white blood cells (WBC), which have been associated earlier with alcohol-induced genotype-specific changes in placental tissue. METHODS:Microarray-based comparative genomic hybridization (aCGH) was used to detect potential submicroscopic chromosomal abnormalities, and developmental as well as phenotypic information about twins were collected. Traditional bisulfite sequencing was used for DNA methylation analysis. RESULTS:Microarray-based comparative genomic hybridization revealed a microdeletion 18q12.3-q21.1. in affected twin, residing in a known 18q deletion syndrome region. This syndrome has been associated with growth restriction, developmental delay or intellectual deficiency, and abnormal facial features in previous studies, and thus likely explains the phenotypic discordancy between the twins. We did not observe association between WBCs' DNA methylation profile and PAE, but interestingly, a trend of decreased DNA methylation at the imprinting control region was seen in the twin with prenatal growth retardation at birth. CONCLUSIONS:The microdeletion emphasizes the importance of adequate chromosomal testing in examining the etiology of complex alcohol-induced developmental disorders. Furthermore, the genotype-specific decreased DNA methylation at the IGF2/H19 locus cannot be considered as a biological mark for PAE in adult WBCs.

SUBMITTER: Kahila H

PROVIDER: S-EPMC7196488 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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18q12.3-q21.1 microdeletion detected in the prenatally alcohol-exposed dizygotic twin with discordant fetal alcohol syndrome phenotype.

Kahila Hanna H Marjonen Heidi H Auvinen Pauliina P Avela Kristiina K Riikonen Raili R Kaminen-Ahola Nina N

Molecular genetics & genomic medicine 20200225 4

<h4>Background</h4>A pair of dizygotic twins discordantly affected by heavy prenatal alcohol exposure (PAE) was reported previously by Riikonen, suggesting the role of genetic risk or protective factors in the etiology of alcohol-induced developmental disorders. Now, we have re-examined these 25-year-old twins and explored genetic origin of the phenotypic discordancy reminiscent with fetal alcohol syndrome (FAS). Furthermore, we explored alterations in DNA methylation profile of imprinting contr ...[more]

PMID: 32096599

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Project description:Neurocognitive effects of prenatal alcohol exposure in adulthood are not well documented. Questions persist regarding the extent to which there are specific, measurable effects beyond those associated with global ability deficits, whether individuals without the full fetal alcohol syndrome (FAS) demonstrate alcohol-related cognitive impairments, and whether observed memory effects are specific to a particular modality, i.e., verbal vs. visual/spatial domains.In this study, verbal and nonverbal selective reminding paradigms were used to assess memory function in 234 young adults (M age: 22.78, SD: 1.79). Alcohol exposure was quantified prenatally. Alcohol groups included: Individuals with physical effects of alcohol exposure (Dysmorphic group, n = 47); Exposed individuals without such effects (n = 74). Contrast groups included: Controls (n = 59) matched for ethnicity, socioeconomic status, and hospital of birth; Special Education contrast group (n = 54) included to control for disability status. Memory outcomes entailed total recall, delayed recall, and measures of encoding and retrieval, and learning over trials as indexed by slope.Results indicated that Dysmorphic individuals were significantly less efficient in memory performance than Controls on all of the outcomes measured, but they did not differ from those in the Special Education contrast group. The nondysmorphic, alcohol-exposed group was intermediate in their performance, suggesting a continuum of effects of prenatal exposure. Evaluation of the encoding and retrieval aspects of memory performance indicated that learning rather than forgetting accounted for the deficits associated with prenatal alcohol exposure. Finally, no interaction was found between modality of presentation (verbal and nonverbal) and effects of alcohol exposure on memory performance.These findings indicate that prenatal alcohol exposure is associated with persistent and specific effects on memory performance, and these problems result from less efficient encoding of information across both verbal and nonverbal modalities. Education and training efforts with this clinical group should take these characteristics into account.

Project description:OBJECTIVE:Whether the use of assisted reproductive technologies (ART) affects the outcome of twin pregnancies is still a matter of debate. Previous studies have evaluated the association between birth weight and ART, without a clear distinction between fetal growth restriction (FGR), a condition at higher risk of adverse outcome, and constitutionally small for gestational age (SGA) fetuses. The aim of this study was to determine whether dichorionic (DC) twin pregnancies obtained by ART have a greater risk of developing FGR, defined by accurate ultrasound criteria, than those spontaneously conceived (SC), and to compare the severity of ultrasound features in the growth restricted fetuses. METHODS:A retrospective study was conducted on DC twin pregnancies delivered between 2010 to 2018 at a tertiary hospital. Twin pregnancies conceived spontaneously were compared with those obtained via in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI), after exclusion of cases with major fetal or uterine malformations. The primary outcome was the incidence of FGR. Secondary outcome was the rate of SGA neonates, defined by a birth weight less than the 10th percentile. The ultrasound characteristics of the growth restricted fetuses in the two groups were also compared. The groups were compared using univariate and multivariate analyses. RESULTS:Six hundred and seventy-eight DC twin pregnancies were identified. Of these, 367 (54.1%) conceived via IVF/ICSI and 311 (45.9%) conceived spontaneously. The incidence of FGR was not significantly different between the ART and the SC groups (7.9% vs 8.4% respectively, p = 0.76, adjusted OR 0.84, 95% CI 0.53-1.32). Growth restricted fetuses of the two groups showed similar occurrence of an estimated fetal weight less than the 3rd percentile, similar abnormalities in Doppler studies and similar gestational age at diagnosis. There was no difference in the incidence of delivery of an SGA neonate (p = 0.47) or in the rate of maternal complications and preterm delivery between the groups. CONCLUSIONS:Twin pregnancies conceived by assisted reproductive technologies do not have a higher risk of ultrasound-diagnosed FGR than spontaneously conceived twin pregnancies, and fetuses diagnosed with growth restriction in the two groups show similar severity of the ultrasound findings.

Dataset Information

18q12.3-q21.1 microdeletion detected in the prenatally alcohol-exposed dizygotic twin with discordant fetal alcohol syndrome phenotype.

Publications

18q12.3-q21.1 microdeletion detected in the prenatally alcohol-exposed dizygotic twin with discordant fetal alcohol syndrome phenotype.

Similar Datasets

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