Genetic analysis of two Chinese pedigrees with 3-M syndrome caused by CUL7 compound heterozygous variants
Objective To explore the clinical features and genetic etiology of two Chinese pedigrees affected with 3-M(Miller-Mukusick-Malvaux)syndrome.Methods Two Chinese pedigrees with 3-M syndrome admitted to Linyi Peo-ple's Hospital in September 2022 and June 2023 were selected as the research objects.Clinical data of the family mem-bers was collected,and the peripheral blood was selected for whole exome sequencing(WES)after informed consent.Candidate variants were verified by Sanger sequencing and pathogenicity assessment was conducted.Prenatal diagnosis was performed for high-risk fetuses in two pedigrees.Results The proband of pedigree 1 was 18-weeks pregnant with short stature,abnormal face and congenital dislocation of the hip at birth.WES detected compound heterozygous vari-ants of CUL7 gene:c.4333C>T(p.R1445∗),c.3291_3294del(p.H1098Cfs∗42),inherited from the father and mother,respectively.The younger brother of the proband carried the same variants.According to the American Society for Medical Genetics and Genomics(ACMG)guidelines,both c.4333C>T and c.3291_3294del were judged to be path-ogenic variants.The fetus carried the c.4333C>T variant.The proband from pedigree 2 showed short height,special face,scoliosis,pterygous scapular bone,bilateral oblique finger,short fifth finger,etc.The proband was found to har-bor c.3823del(p.R1275Vfs∗34)and c.758del(p.L253Rfs∗2)compound heterozygous variants of CUL7 gene,which inherited from mother and father,respectively.And they were judged to be pathogenic variants and suspected pathogenic variants.Maternal prenatal diagnosis indicated that the fetus carried the c.758 del variant.Conclusion In this study,three patients with 3-M syndrome were diagnosed in two pedigrees.Two compound heterozygous variants of CUL7 gene were probably the genetic causes of pedigree 1 and pedigree 2,respectively.Above findings expanded the variation spec-trum of CUL7 gene in 3-M syndrome and provided a basis for genetic counseling and prenatal diagnosis.
NETL
NSTL
万方数据
