TSPYL4 – Dravet syndrome

TSPYL4 (HGNC:21559) has been implicated as a candidate contributor to Dravet syndrome (MONDO:0100135), although the current evidence is limited. In a 2012 study of Chinese children with severe epilepsy (PMID:22848613), 18 patients with Dravet syndrome were evaluated, and in one patient a rare, inherited missense variant, c.178G>C (p.Gly60Arg), in TSPYL4 was identified. This observation was made in the context of co‐occurring mutations in more established Dravet syndrome genes such as SCN1A and PCDH19, complicating the assignment of an independent pathogenic role to TSPYL4. No additional unrelated probands or segregation data supporting TSPYL4, such as affected relatives carrying the variant, have been reported (PMID:22848613). Furthermore, functional assessment studies have not yet provided conclusive evidence regarding the mechanism by which TSPYL4 may contribute to the disease phenotype. Consequently, the overall gene‐disease association is classified as Limited, and further independent studies and functional analyses are necessary to clarify TSPYL4’s role in Dravet syndrome. Key take‐home sentence: Although inclusion of TSPYL4 in epilepsy genetic panels shows promise, current evidence is insufficient for definitive clinical interpretation.

References

• PloS One • 2012 • Identification of SCN1A and PCDH19 mutations in Chinese children with Dravet syndrome PMID:22848613

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