Compound heterozygous mutations in SHQ1 have been associated with a rare and severe neurological disorder characterized by global developmental delay (GDD), cerebellar degeneration coupled with seizures, and early-onset dystonia. Currently, only five affected individuals have been documented in the literature. Here, we report three children from two unrelated families harboring a homozygous variant in the gene but with a milder phenotype than previously described. The patients had GDD and seizures. Magnetic resonance imaging analyses revealed diffuse white matter hypomyelination. Sanger sequencing confirmed the whole-exome sequencing results and revealed full segregation of the missense variant (SHQ1:c.833 T > C; p.I278T) in both families. We performed a comprehensive in silico analysis using different prediction classifiers and structural modeling of the variant. Our findings demonstrate that this novel homozygous variant in SHQ1 is likely to be pathogenic and leads to the clinical features observed in our patients.
Bibliographical noteKAUST Repository Item: Exported on 2023-02-27
Acknowledged KAUST grant number(s): REI/1/4446-01
Acknowledgements: Funds were received from the King Salman Center for Disability Research (RAC/ORA#2180004) (NK). STA was supported by the King Abdullah University of Science and Technology (KAUST) through the baseline fund and Award No. REI/1/4446-01 from the Office of Sponsored Research (OSR). We thank the families, the Center for Genomic Medicine Core Laboratories, the Research Advisory Council Committees, and the KFSHRC Purchasing Departments for facilitating and expediting our requests. We extend our special thanks to the King Salman Center for Disability Research (KSCDR; RAC/ORA#2180004, NK) for grant support during the study. For computer time, this research used the resources of the Supercomputing Laboratory at King Abdullah University of Science & Technology (KAUST) in Thuwal, Saudi Arabia.