An amino acid deletion inSZT2 in a family with non-syndromic intellectual disability

Abstract

Autosomal recessive intellectual disability (ID) is characterized by extensive genetic heterogeneity. Recently, three mutations in SZT2 were reported in two unrelated children with unexplained infantile epileptic encephalopathy with severe ID. Here we report a European American family with three children having non-syndromic mild or moderate ID without seizures. Whole-exome sequencing of three affected siblings revealed a three base pair deletion (c.4202_4204delTTC) located in a 19 mb autozygous region on chromosome 1, leading to an amino acid deletion (p.Phe1401del) in SZT2. All three children were homozygous for the deletion and their parents were heterozygous as expected in autosomal recessive inheritance. SZT2 is highly expressed in neuronal tissues and regulates seizure threshold and neuronal excitation in mice. We conclude that the disruption of SZT2 with some residual function might lead to mild or moderate ID without seizures.

Figure 1. Studied family and identified SZT2 mutation.

A) The pedigree of the family and pictures of the affected siblings corresponding to their position in the pedigree. B) Electropherograms showing identified mutation in SZT2 in the family. C) The longest shared autozygous region of 19 mb in three siblings discovered by whole-exome sequencing (on chromosome 1). Black, yellow, and gray denote homozygous, heterozygous, and missing genotypes, respectively. Red lines indicate the borders of the shared autozygous region. D) Conservation of SZT2: Phenylalanine 1401 is conserved among mammals (mouse, rat, house cat) and fish (tilapia).