Do the exome: A case of Williams-Beuren syndrome with severe epilepsy due to a truncating de novo variant in GABRA1

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• 作者：Bernt Popp^a ; ^{bernt.popp@uk-erlangen.de" class="auth_mail" title="E-mail the corresponding author} ; Regina Trollmann^b ; Christian B&uuml ; ttner^a ; Almuth Caliebe^c ; Christian T. Thiel^a ; Ulrike H&uuml ; ffmeier^a ; André ; Reis^a ; Christiane Zweier^a
• 关键词：Williams-Beuren syndrome ; Deletion ; GABRA1 ; De novo mutation ; Epilepsy ; Exome
• 刊名：European Journal of Medical Genetics
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：59
• 期：10
• 页码：549-553
• 全文大小：906 K

文摘

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.