Common genetic variation in the Angelman syndrome imprinting centre affects the imprinting of chromosome 15.

European Journal of Human Genetics : EJHG
Jasmin BeygoB Horsthemke

Abstract

Angelman syndrome (AS) is a rare neurogenetic imprinting disorder caused by the loss of function of UBE3A. In ~3-5% of AS patients, the disease is due to an imprinting defect (ID). These patients lack DNA methylation of the maternal SNRPN promotor so that a large SNRPN sense/UBE3A antisense transcript (SNHG14) is expressed, which silences UBE3A. In very rare cases, the ID is caused by a deletion of the AS imprinting centre (AS-IC). To search for sequence alterations, we sequenced this region in 168 patients without an AS-IC deletion, but did not detect any sequence alteration. However, the AS-IC harbours six common variants (five single nucleotide variants and one TATG insertion/deletion variant), which constitute five common haplotypes. To determine if any of these haplotypes is associated with an increased risk for an ID, we investigated 119 informative AS-ID trios with the transmission disequilibrium test, which is a family-based association test that measures the over-transmission of an allele or haplotype from heterozygous parents to affected offspring. By this we observed maternal over-transmission of haplotype H-AS3 (p = 0.0073). Interestingly, H-AS3 is the only haplotype that includes the TATG deletion allele. We conclu...Continue Reading

References

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Jun 10, 2009·Proceedings of the National Academy of Sciences of the United States of America·Yotam KaufmanRuth Shemer
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Dec 3, 2016·Epigenetics : Official Journal of the DNA Methylation Society·David MonkUNKNOWN Nomenclature group of the European Network for Human Congenital Imprinting Disorders
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Jan 13, 2019·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Federica Maria ValenteFlavia Cerrato

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Citations

Oct 4, 2020·Scientific Reports·Serena MichelettiElisa Fazzi
Mar 5, 2021·Frontiers in Genetics·Aron Judd P Mendiola, Janine M LaSalle
Jun 29, 2021·Frontiers in Neurology·Altynshash JaxybayevaKymbat Jamanbekova

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BETA
PCR

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Geneious

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Angelman Syndrome

Angelman syndrome is a neurogenetic imprinting disorder caused by loss of the maternally inherited UBE3A gene and is characterized by generalized epilepsy, limited expressive speech, sleep dysfunction, and movement disorders. Here is the latest research.

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