Background: West syndrome (WS) is an epileptic encephalopathy (EE) that begins in children 4-7 months of age (in rare cases older than 2 years). To date, over 30 genes that have been reported to be related to WS. Reports involving the extremely rare pathogenic gene, transducin beta-like 1-X- linked receptor 1(TBL1XR1) are quite limited.
Methods: We performed exome sequencing (ES) of family trios for this infant. We also collected and summarized the clinical data for reported heterozygous germline variants of TBL1XR1. Moreover, we reviewed all published cases and summarized the clinical features and genetic variants of TBL1XR1.
Results: ES revealed a de novo variant in TBL1XR1 [NM_024665.5: exon4: c.187G > A (p.Glu63Lys)]. This variant was classified as likely pathogenic according to the ACMG (American College of Medical Genetics and Genomics) guidelines and was verified by Sanger sequencing. Further conservation analyses revealed a high conservation among several species. There was clinical heterogeneity among all patients with TBL1XR1-related West syndrome.
Conclusion: Our results expand the pathogenic variant spectrum of TBL1XR1 and strengthen the pathogenic evidence of TBL1XR1 in West syndrome.
Keywords: TBL1XR1, development delay, epilepsy; West syndrome; variant.
© 2022 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.