PMID: 32529990Jun 13, 2020Paper

Psychiatric features and variable neurodevelopment outcome in four females with IQSEC2 spectrum disorder

Journal of Genetics
Andrea AccogliYannis Trakadis

Abstract

IQSEC2 is an X-linked gene highly expressed at the excitatory synapses where it plays a crucial role in α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor trafficking and synaptic plasticity. To date, several males and females with severe to profound intellectual disability have been reported harbouring frameshift and nonsense variants in this gene, whereas a milder phenotype has been recognized in females carrying missense pathogenic variants. Here, we report two novel IQSEC2 variants in four females with psychiatric features and otherwise variable cognitive impairment. A female (case 1) with severe verbal language learning disorder and a psychotic episode (precipitated by exposure to anti-contraceptive pill) harboured a de novo pathogenic frameshift variant (c.1170dupG,p.Gln391Alafs*5), whereas the female proband of family 2, displaying severe psychomotor regression and complex psychiatric features carried a missense variant of uncertain significance (c.770G[A,p.Ser257Asn) that was maternally inherited. Skewed X-inactivation was noted in the carrier mother. The maternal aunt, affected by schizophrenia, was found to bear the same IQSEC2 variant. We discuss the variable clinical presentation of IQSEC2 spectrum disord...Continue Reading

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