ST3GAL3 deficiency with autistic behavior: First description of frameshift variant and literature review

ST3GAL-III deficiency is an extremely rare genetic disease caused by pathogenic variants in the ST3GAL3 gene. There are two extremely rare disorders caused by homozygous mutations in the ST3GAL3 gene: developmental and epileptic encephalopathy 15 (MIM#615006) and intellectual developmental disorder, autosomal recessive 12 (MIM#611089). To date, no homozygous frameshift mutation in the ST3GAL3 gene has been identified that results in ST3GAL-III deficiency. The present study describes the first pathogenic homozygous frameshift variant (NM_174964.4:c.1113dup, p. Glu372ArgfsTer14) in the ST3GAL3 gene, which was identified by Whole-Exome sequencing and confirmed by Sanger sequencing. This novel mutation is responsible for developmental delay, speech impairment, epilepsy, hypotonia, intellectual disability, and behavioral issues in the proband. Eventually, we provide a case -based review of the clinical features associated with ST3GAL3 mutation. We compared our findings to previously reported cases, suggesting that developmental delay, speech impairment and intellectual disability are the main clinical features in ST3GAL3 deficient patients. Further studies would be beneficial to determine which genetic variants cause intellectual and behavioral problems, since they are highly diverse and poorly understood.