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A novel intronic variant in UBE3A identified by genome sequencing in a patient with an atypical presentation of Angelman syndrome
Author(s) -
Curtis Meredith,
Baribeau Danielle,
Walker Susan,
Carter Melissa,
Costain Gregory,
Lamoureux Sylvia,
Liston Eriskay,
Marshall Christian R.,
Reuter Miriam S.,
Snell Meaghan,
Summers Jane,
Vorstman Jacob,
Jobling Rebekah K.
Publication year - 2020
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.61740
Subject(s) - angelman syndrome , ube3a , genetics , neurodevelopmental disorder , biology , rna splicing , allele , genetic testing , presentation (obstetrics) , rna , medicine , gene , ubiquitin ligase , ubiquitin , radiology
Angelman syndrome (AS) is a genetic neurodevelopmental disorder caused by loss or deficient expression of UBE3A on the maternally inherited allele. In 10–15% of individuals with a clinical diagnosis of AS, a molecular diagnosis cannot be established with conventional testing. We describe a 13‐year‐old male with an atypical presentation of AS, who was found to have a novel, maternally inherited, intronic variant in UBE3A (c.3‐12T>A) using genome sequencing (GS). Targeted sequencing of RNA isolated from blood confirmed the creation of a new acceptor splice site. These GS results ended a six‐year diagnostic odyssey and revealed a 50% recurrence risk for the unaffected parents. This case illustrates a previously unreported splicing variant causing AS. Intronic variants identifiable by GS may account for a proportion of individuals who are suspected of having well‐known genetic disorders despite negative prior genetic testing.