Preimplantation genetic testing-M for pathogenic variant in CTC1 gene causing cerebroretinal microangiopathy

Cerebroretinal microangiopathy with calcifications and cysts (CRMCC) is an autosomal recessive genetic and multisystem disorder characterized by extensive intracranial calcifications, leukoencephalopathy, and retinal vascular abnormalities, which is primarily caused by mutations in the CTC1 gene. Preimplantation genetic testing (PGT) is a procedure that helps patients choose embryos free of chromosome abnormalities and monogenic diseases for uterine transfer, preventing serious genetic disorders from being passed on to future generations. Here we introduce a family with fetal malformations due to CRMCC. We aimed to identify the pathogenic variants in a family with fetal malformations due to CRMCC and to utilize PGT to prevent the transmission of this genetic disorder to the next generation.

Whole-exome sequencing (WES) performed on the aborted fetus suggested a novel homozygous mutation in CTC1, and Sanger sequencing revealed that this mutation is inherited from the parents.

The couple decided to undergo PGT for monogenic disorders to avoid disease transmission and achieve a healthy birth. Blastocyst trophectoderm biopsy was performed for whole-genome amplification and next-generation sequencing (NGS)-based PGT to select unaffected embryos, which resulted in the birth of healthy babies.

This is a novel mutation of CTC1 causing CRMCC and also the first PGT case for CRMCC, which expanded the spectrum of CTC1 mutations and will provide a solution for patients to bear healthy offspring using PGT. Furthermore, our study reconfirms the importance of genetic tests in aborted fetuses and genetic counseling.