title: 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.
authors: Dr. John T. Macdonald Department of Human Genetics and John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, Florida, United States of America.
authors: Michelle
authors: M
authors: Falcone
authors: Kemal O
authors: KO
authors: Yariz
authors: David B
authors: DB
authors: Ross
authors: Joseph
authors: J
authors: Foster
authors: Ibis
authors: I
authors: Menendez
authors: Mustafa
authors: M
authors: Tekin
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D000596:Amino Acids; D002648:Child; D020090:Chromosome Segregation; D004252:DNA Mutational Analysis; D019066:Facies; D005260:Female; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D016415:Sequence Alignment; D017384:Sequence Deletion
chemical_list: D000596:Amino Acids; D009419:Nerve Tissue Proteins; C584145:SZT2 protein, human