Genes and Genomics

The Genetics Society of Korea (한국유전학회)
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A novel homozygous mutation in SZT2 gene in Saudi family with developmental delay, macrocephaly and epilepsy

  • Naseer, Muhammad Imran (Center of Excellence in Genomic Medicine Research (CEGMR), King Abdulaziz University) ;
  • Alwasiyah, Mohammad Khalid (Center of Excellence in Genomic Medicine Research (CEGMR), King Abdulaziz University) ;
  • Abdulkareem, Angham Abdulrahman (Center of Excellence in Genomic Medicine Research (CEGMR), King Abdulaziz University) ;
  • Bajammal, Rayan Abdullah (Aziziah Maternity & Children Hospital) ;
  • Trujillo, Carlos (Genetics Unit, Erfan & Bagedo Hospital) ;
  • Abu-Elmagd, Muhammad (Center of Excellence in Genomic Medicine Research (CEGMR), King Abdulaziz University) ;
  • Jafri, Mohammad Alam (Center of Excellence in Genomic Medicine Research (CEGMR), King Abdulaziz University) ;
  • Chaudhary, Adeel G. (Center of Excellence in Genomic Medicine Research (CEGMR), King Abdulaziz University) ;
  • Al-Qahtani, Mohammad H. (Center of Excellence in Genomic Medicine Research (CEGMR), King Abdulaziz University)
  • Received : 2017.09.12
  • Accepted : 2018.02.23
  • Published : 2018.11.30
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Abstract

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.

Keywords

References

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