Objective To investigate the genetic characteristics of fetuses with Cardiac-Urogenital syndrome(CUGS)in order to clarify the etiology and provide genetic counseling and fertility guidance.Methods One fetus with CUGS diag-nosed in Gansu Provincial Maternity and Child-care Hospital in 2022 was selected as the study population.Fetal amniotic fluid and peripheral blood of its parents were collected,genomic DNA was extracted,and family whole exome sequencing(trio-WES)and low throughput whole genome sequencing(CNV-seq)were performed.Sanger sequencing technology was applied to perform lineage validation of suspected pathogenic mutation loci.Results trio-WES showed the presence of the c.3301-2A＞C classical shear variant in intron 25 of the fetal MYRF gene,which was a de novo heterozygous variant with both parents being wild type.This variant was not retrieved from the literature and was not included in the general human carrier frequency databases such as thousand genomes,gnomAD,etc.It is a rare variant.The variant was assessed as likely patho-genic(PVS1+PM2_Supporting)according to the American College of Medical Genetics and Genomics(ACMG)guidelines.Conclusion Ultrasound-based combined with whole-exome sequencing can rapidly and reliably confirm the diagnosis of chil-dren with CUGS and support clinical decision making in fetuses.Meanwhile,we identified one novel and spontaneous muta-tion in MYRF gene,which has not been reported at home and abroad,expanding the spectrum of pathogenic mutations in MYRF gene and providing theoretical basis for clinical diagnosis and genetic counseling of the disease.
维普
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