A novel homozygous mutation in SZT2 gene in Saudi family with developmental delay, macrocephaly and epilepsy
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.
KeywordsSZT2 gene Epilepsy Intellectual disability Saudi family
This project was funded by the National Plan for Science, Technology and Innovation (MAARIFAH)—King Abdul-Aziz City for Science and Technology—the Kingdom of Saudi Arabia—award number (12-BIO3059-03). The authors also, acknowledge with thanks Science and Technology Unit, King Abdul-Aziz University for technical support.
Compliance with ethical standards
Conflict of interest
All authors (1) Muhammad Imran Naseer, (2) Mohammad Khalid Alwasiyah, (3) Angham Abdulrahman Abdulkareem, (4) Rayan Abdullah Bajammal, (5) Carlos Trujillo, (6) Muhammad Abu-Elmagd, (7) Mohammad Alam Jafri, (8) Adeel G. Chaudhary, (9) Mohammad H. Al-Qahtani declare that they have no conflict of interest.
This study was approved by the Institutional Review Board Committees at CEGMR King Abdulaziz University Jeddah Saudi Arabia.
Written informed consent was obtained from all study participants from this family.