Novel compound heterozygous mutation and phenotype in the tetratricopeptide repeat-like domain of the GEMIN5 gen e in two Chinese families

Background GEMIN5 is an RNA-binding protein that regulates multiple molecular functions, including splicing, localisation, translation, and mRNA stability. GEMIN5 mutations present a syndrome centred on cerebellar dysplasia, including motor dysfunction, developmental delay, cerebellar atrophy, and hypotonia. Cases We report three patients from two families with novel compound heterozygous mutations in the tetratricopeptide repeat-like domain of the GEMIN5 gene who presented with motor dysfunction, developmental delay, and ataxia syndrome. Novel variants were identified: c.2551_c.2552delCT (Leu851Glufs*30) and c.2911 C > G (Gln971Glu) in Family 1, and c.3287 T > C (Leu1096Pro) and c.2882 G > C (Trp961 Ser) in Family 2, which were inherited from their parents. Moreover, infantile spasms syndrome(ISs) was diagnosed in the family. Conclusion We report the first case of ISs caused by GEMIN5 gene mutations. Our cases expand on GEMIN5 variants and neurological phenotypes, reinforcing the crucial impact of tetratricopeptide repeat-like domain variants in the GEMIN5 gene.