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

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Kahila , H , Marjonen , H , Auvinen , P , Avela , K , Riikonen , R & Kaminen-Ahola , N 2020 , ' 18q12.3-q21.1 microdeletion detected in the prenatally alcohol-exposed dizygotic twin with discordant fetal alcohol syndrome phenotype ' , Molecular Genetics & Genomic Medicine , vol. 8 , no. 4 , 1192 . https://doi.org/10.1002/mgg3.1192

Title: 18q12.3-q21.1 microdeletion detected in the prenatally alcohol-exposed dizygotic twin with discordant fetal alcohol syndrome phenotype
Author: Kahila, Hanna; Marjonen, Heidi; Auvinen, Pauliina; Avela, Kristiina; Riikonen, Raili; Kaminen-Ahola, Nina
Contributor: University of Helsinki, Department of Obstetrics and Gynecology
University of Helsinki, Medicum
University of Helsinki, Environmental Epigenetics Laboratory
University of Helsinki, HUSLAB
University of Helsinki, Environmental Epigenetics Laboratory
Date: 2020-04
Language: eng
Number of pages: 9
Belongs to series: Molecular Genetics & Genomic Medicine
ISSN: 2324-9269
URI: http://hdl.handle.net/10138/318541
Abstract: 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.
Subject: 3111 Biomedicine
1182 Biochemistry, cell and molecular biology
18q deletion syndrome
comparative genomic hybridization array
DNA methylation
fetal alcohol spectrum disorders
fetal alcohol syndrome
growth retardation
IGF2/H19
prenatal alcohol exposure
twins
DNA METHYLATION
MRI
IGF2
INDIVIDUALS
H19
18Q DELETIONS
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