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.

SHQ1中的复合杂合突变与一种罕见且严重的神经系统疾病有关，其特征是整体发育迟缓 (GDD)、小脑退化伴癫痫发作和早发性肌张力障碍。目前，文献中仅记录了五个受影响的个体。在这里，我们报告了来自两个无关家庭的三个孩子，他们在该基因中携带纯合变体，但表型比之前描述的要温和。患者有 GDD 和癫痫发作。磁共振成像分析显示弥漫性白质髓鞘形成不足。Sanger 测序证实了全外显子组测序结果并揭示了错义变异体 ( SHQ1)的完全分离:c.833 T > C; p.I278T）在两个家庭中。我们使用不同的预测分类器和变体的结构建模进行了全面的计算机分析。我们的研究结果表明， SHQ1中的这种新型纯合变异可能具有致病性，并导致在我们的患者中观察到的临床特征。