Do the exome: A case of Williams-Beuren syndrome with severe epilepsy due to a truncating de novo variant in GABRA1.
Williams-Beuren syndrome (WBS) is a relatively common, clinically recognizable microdeletion syndrome. In most cases the typical heterozygous deletion of 1.5 Mb on chromosome 7q11.23 spanning about 26 genes can be identified. Also some larger or smaller atypical deletions have been reported and associated with additional or atypical phenotypic aspects. We report on an individual with typical WBS due to the common deletion and with refractory infantile spasms. Using trio-exome sequencing, we identified a de novo truncating variant c.1200del, p (Lys401Serfs*25) in GABRA1 as the likely cause of the early onset epilepsy. This unique case not only allows to further define the phenotypic spectrum of infantile epileptic encephalopathy associated with rare de novo GABRA1 variants but exemplifies the need for a sensitive review of unclear associations in clinically defined syndromes and for extended diagnostic work-up in individuals with unusual presentations of a genetically confirmed diagnosis.
Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany. Electronic address: bernt.popp@uk-erlangen.de.
Bernt
B
Popp
Department of Pediatrics, University Hospital for Children and Adolescents, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
Regina
R
Trollmann
Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
Christian
C
Büttner
Institute of Human Genetics, Christian-Albrechts-University Kiel & University, Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
Almuth
A
Caliebe
Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
Christian T
CT
Thiel
Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
Ulrike
U
Hüffmeier
Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
André
A
Reis
Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
Christiane
C
Zweier
D004827:Epilepsy / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D059472:Exome / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D011963:Receptors, GABA-A / Q000235:genetics*; D013036:Spasms, Infantile / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D018980:Williams Syndrome / Q000235:genetics* / Q000503:physiopathology
C546240:GABRA1 protein, human; D011963:Receptors, GABA-A
De novo mutation; Deletion; Epilepsy; Exome; GABRA1; Williams-Beuren syndrome