ObjectiveTo investigate the clinical manifestations and molecular genetic characteristics of type I patients with or without ocular abnormalities caused by COL4A1 gene variation.

MethodsA family investigation study was conducted to collect clinical data of a child born in September 2022 in the Fourth Hospital of Shijiazhuang with lesions involving multiple organs such as eyes and brain. Whole genome sequencing was performed on the patient and his parents to select relevant variant, and the variant site was verified by Sanger sequencing. The pathogenicity of the variant sites was evaluated according to ACMG guidelines and bioonline software. Summarize and analyze the previous literature cases.

ResultsWhole genome sequencing technology found that the patient carried COL4A1 gene c. 2044G>C(p.Gly682Arg) missense variation. Sanger sequencing confirmed that the variant was not detected in the peripheral blood samples of the parents of the patient, suggesting that it was a new variant. According to ACMG clinical guidelines, this variant was identified as a suspected pathogenic variant. Compared with previously reported cases, it was found that in addition to typical clinical features such as epilepsy, ventricular dilatation, dysplasia of corpus callosum, congenital cataract, congenital microeyeball, fetal growth restriction, and abnormal myocardial enzyme profile, the patient also showed rare features such as cerebellar dysplasia.

ConclusionsThe missense variation of COL4A1 gene c.2044G>C may be the cause of this disease. The detection of COL4A1 gene should be improved as soon as possible for fetal ventricular dilatation, corpus callosum dysplasia and fetal growth restriction during pregnancy.