Abstract
Mosaicism for a cell line in which all chromosome pairs consists of two identical copies derived from only one of the parents, a so called genome-wide uniparental isodisomy (gwUPiD) is a rare phenomenon.
We report on a newborn presenting with clinical characteristics of Beckwith-Wiedemann syndrome (BWS), birth weight 2610g (~P80), facial dysmorphisms including ear lobe creases and nevus flammeus, umbilical hernia, diastastis recti, hepatomegaly and hypoglycemia due to hyperinsulinism.
Beckwith Wiedemann syndrome (OMIM#130650) is characterized by prenatal and postnatal overgrowth, hemihyperplasia, macroglossia and an increased frequency of embryonic tumors. In 60-70% of the patients, an epigenetic error at either the H19DMR (imprinting control region, ICR1) or KvDMR (ICR2), controlling the appropriate allelic expression of the paternal IGF2 and maternal CDKN1C genes, causes the clinical phenotype. In 10-15% of cases, the cause is presence of two paternally derived copies of chromosome region 11p15, a so called paternal uniparental disomy (UPD) 11p15. A small percentage of cases are caused by maternal translocations/inversions or paternal duplications (2-3%) or mutation in CDKN1C (5-7%).
To confirm clinical diagnosis, a methylation test was performed which showed hypermethylation of H19DMR, corresponding to a paternal UPD 11p. To exclude a chromosomal rearrangement, karyotyping and SNP-array analysis (Illumina CytoSNP-850k) were performed on DNA isolated from peripheral blood. SNP-array showed a gwUPiD in a high percentage of cells (>95%). No additional clinically relevant copy number alterations were observed and karyotyping showed a normal female karyotype. Since only mosaicism for gwUPiD can be compatible with life we decided to perform additional SNP-array analysis on saliva derived DNA, which showed normal biparental contribution without any indication for the presence of gwUPiD cells.
In conclusion, we present a rare case of BWS in a newborn caused by mosaic gwUPiD.
Original language | English |
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Publication status | Published - 5 Apr 2016 |
Event | 13th International Congress of Human Genetics (ICHG2016): “Frontier of Genomic Medicine: Message from the Past to the Future.” - Kyoto International Conference Center, Annex 2, Kyoto, Japan Duration: 3 Apr 2016 → 7 Apr 2016 Conference number: 13th http://www.ichg2016.org/ |
Conference
Conference | 13th International Congress of Human Genetics (ICHG2016) |
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Abbreviated title | ICHG2016 |
Country/Territory | Japan |
City | Kyoto |
Period | 3/04/16 → 7/04/16 |
Internet address |
Keywords
- Clinical Genetics and Dysmorphology
- Chromosomal disorders
- Cytogenetics
- Molecular cytogenetic technologies (eg, FISH, microarrays, etc.)