IQSEC2‐related encephalopathy in males due to missense variants in the pleckstrin homology domain. Issue 1 (6th April 2022)

• Record Type: Journal Article
• Authors: Shoubridge, Cheryl; Dudding‐Byth, Tracy; Pasquier, Laurent; Goel, Himanshu; Yap, Patrick; McConnell, Vivienne
• Is Part Of: Clinical genetics. Volume 102:Issue 1(2022)
• Page Start: 72
• Page End: 77
• Publication Date: 2022-04-06
• Subjects: epilepsy -- IQSEC2 -- pathogenic sequence variant -- PH domain; Medical genetics -- Periodicals; 616.0420
• DOI: 10.1111/cge.14136
• Languages: English
• ISSNs: 0009-9163

Abstract

Abstract: Pathogenic variants in IQ motif and SEC7 domain containing protein 2 ( IQSEC2 ) gene cause a variety of neurodevelopmental disorders, with intellectual disability as a uniform feature. We report five cases, each with a novel missense variant in the pleckstrin homology (PH) domain of the IQSEC2 protein. Male patients all present with moderate to profound intellectual disability, significant delays or absent language and speech and variable seizures. We describe the phenotypic spectrum associated with missense variants in PH domain of IQSEC2, further delineating the genotype–phenotype correlation for this X‐linked gene. Abstract : We report five novel missense variants in the pleckstrin homology (PH) domain of the IQSEC2 protein. Male patients all present with moderate to profound intellectual disability, significant delays or absent language and speech and variable seizures, consistent with the features in other reported cases and highlights the importance of the PH domain for IQSEC2 function.