A novel homozygous mutation in SZT2 gene in Saudi family with developmental delay, macrocephaly and epilepsy.
PMID 30315519 | DOI 10.1007/s13258-018-0673-5 · Genes & genomics · 2018 · View on PubMed ↗
Epileptic encephalopathies are genetically heterogeneous disorders which leads to epilepsy and cause neurological disorders. Seizure threshold 2 (SZT2) gene located on chromosome 1p34.2 encodes protein mainly expressed predominantly in the parietal and frontal cortex and dorsal root ganglia in the brain. Previous studies in mice showed that mutation in this gene can confers low seizure threshold, enhance epileptogenesis and in human may leads to facial dysmorphism, intellectual disability, seizure and macrocephaly. Objective of this study was to find out novel gene or novel mutation related to the gene phenotype. We have identified a large consanguineous Saudi family segregating developmental delay, intellectual disability, epilepsy, high forehead and macrocephaly. Exome sequencing was performed in affected siblings of the family to study the novel mutation. Whole exome sequencing data analysis, confirmed by subsequent Sanger sequencing validation study. Our results showed a novel homozygous mutation (c.9368G>A) in a substitution of a conserved glycine residue into a glutamic acid in the exon 67 of SZT2 gene. The mutation was ruled out in 100 unrelated healthy controls. The missense variant has not yet been reported as pathogenic in literature or variant databases. In conclusion, the here detected homozygous SZT2 variant might be the causative mutation that further explain epilepsy and developmental delay in this Saudi family.
Validated evidence
| Type | Entity | Source evidence | Confidence | Extractor |
|---|---|---|---|---|
| gene | SZT2 | “A novel homozygous mutation in SZT2 gene in Saudi family with developmental delay, macrocephaly and epilepsy.” | 0.98 | hgnc_dict_v1 |
| phenotype | developmental delay | “A novel homozygous mutation in SZT2 gene in Saudi family with developmental delay, macrocephaly and epilepsy.” | 0.98 | phenotype_alias_lexicon_v2 |
| phenotype | epilepsy | “A novel homozygous mutation in SZT2 gene in Saudi family with developmental delay, macrocephaly and epilepsy.” | 0.98 | phenotype_alias_lexicon_v2 |
| phenotype | intellectual disability | “Previous studies in mice showed that mutation in this gene can confers low seizure threshold, enhance epileptogenesis and in human may leads to facial dysmorphism, intellectual disability, seizure and macrocephaly.” | 0.98 | phenotype_alias_lexicon_v2 |
| population | Saudi Arabia | “A novel homozygous mutation in SZT2 gene in Saudi family with developmental delay, macrocephaly and epilepsy. We have identified a large consanguineous Saudi family segregating developmental delay, intellectual disability, epilepsy, high forehead and macrocephaly. The mutation was ruled out in 100 unrelated healthy controls. In conclusion, the here detected homozygous SZT2 variant might be the causative mutation that further explain epilepsy and developmental delay in this Saudi family.” | 0.95 | saudi_context_rules_v1 |
| variant | c.9368G>A | “Our results showed a novel homozygous mutation (c.9368G>A) in a substitution of a conserved glycine residue into a glutamic acid in the exon 67 of SZT2 gene.” | 0.95 | hgvs_regex_v1 |