A novel mutation within intron 17 of the CUL7 gene results in appearance of premature termination codon.

Abstract A couple with five adverse pregnancy history required prenatal diagnosis. The fetus of this study was their fifth pregnancy. The fetus was found NT thickening at 12 weeks and 4 days gestation and the average long bone of limbs retardation 4SD at 27 weeks and 4 days gestation. Karyotype was normal. The next-generation sequencing (NGS) and Sanger sequencing were conducted of this fetus. The compound heterozygous mutations c.3722_3749dup[p.V1252fs*23] and c.3355 + 5 G > A at CUL7 gene were detected. The mutation c.3355 + 5 G > A was a novel mutation within intron 17 of the CUL7 gene. Minigene array was used to verify whether the novel mutation c.3355 + 5 G > A really affected the splicing of CUL7gene. The results showed that the mutation could result in the appearance of premature termination codon. The fetus could be diagnosed as 3 M syndrome. We suggested that close attention needed to be paid to fetuses with intrauterine growth restriction only by ultrasonic and avoid misdiagnosis and missed diagnosis of 3 M syndrome. In addition, our study enriched gene mutations of 3 M syndrome.