稀なCOL1A1バリアントが神経学的異常を伴う患者に二倍体で存在し、重度の眼科的異常を伴わない

COL18A1 encodes the α1 chain of collagen type XVIII, a nonfibrillar collagen expressed in vascular and epithelial basement membranes. Biallelic pathogenic variants in COL18A1 have been associated with Knobloch syndrome, a condition defined by ophthalmologic abnormalities, though patients often have some or all of brain malformations, epilepsy, and intellectual disability. We reviewed our research and clinical databases for patients with seizures and biallelic COL18A1 variants suspected to be pathogenic. Three patients were identified, all of whom had epilepsy and global development impairment, with two having had developmental regression and drug-resistant seizures. None of the patients had severe ophthalmologic disease. All three patients had one heterozygous likely pathogenic frameshift COL18A1 variant on one allele, with the other allele carrying a rare heterozygous missense COL18A1 variant of less certain pathogenicity. These data raise the possibility that COL18A1 disruption could produce phenotypes without severe eye abnormalities but significant neurologic dysfunction.