Submission Details

COLGALT1 was first reported in relation to autosomal recessive brain small vessel disease 3 (BSVD3) in 2018 (Miyatake et al., PMID: 30412317). BSVD3 results from fragility of cerebral vessels causing an increased risk for intracranial bleeding. The clinical findings depend on the timing and location of the intracranial bleed and have been observed in utero and early infancy. Symptoms include developmental delay, spasticity, and porencephaly on brain imaging (Miyatake et al., PMID: 30412317). The COLGALT1 gene encodes the collagen beta galactosyltransferase 1 (ColGalT1) protein. This protein initiates glycosylation of CoL4a1, an important step in the formation of the triple helix of collagen IV (Teunissen et al., PMID: 33709034). At least 5 biallelic COLGALT1 variants (4 missense, 1 splice site) have been reported in humans. This gene-disease relationship is supported by functional evidence including expression studies and rescue experiments (Miyatake et al., PMID: 30412317; Teunissen et al., PMID: 33709034). In summary, there is moderate evidence to support this gene-disease relationship. While more evidence is needed to establish this relationship definitively, no convincing contradictory evidence has emerged. This classification was approved by the ClinGen Congenital Disorders of Glycosylation GCEP on March 6, 2025 (SOP Version 11).