ABSTRACT
OBJECTIVE@#To provide prenatal diagnosis, pedigree analysis and genetic counseling for a pregnant woman who had given birth to a child featuring global developmental delay.@*METHODS@#A pregnant woman who underwent prenatal diagnosis at the Affiliated Hospital of Southwest Medical University in August 2021 was selected as the study subject. Peripheral blood samples were collected from the woman, her husband and child, in addition with amniotic fluid sample during mid-pregnancy. Genetic variants were detected by G-banded karyotyping analysis and copy number variation sequencing (CNV-seq). Pathogenicity of the variant was predicted based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). Candidate variant was traced in the pedigree to assess the recurrence risk.@*RESULTS@#The karyotypes of the pregnant woman, her fetus, and affected child were 46,XX,ins(18)(p11.2q21q22), 46,X?,rec(18)dup(18)(q21q22)ins(18)(p11.2q21q22)mat and 46,XY,rec(18)del(18)(q21q22)ins(18)(p11.2q21q22)mat, respectively. Her husband was found to have a normal karyotype. CNV-seq has revealed a 19.73 Mb duplication at 18q21.2-q22.3 in the fetus and a 19.77 Mb deletion at 18q21.2-q22.3 in her child. The duplication and deletion fragments were identical to the insertional fragment in the pregnant woman. Based on the ACMG guidelines, the duplication and deletion fragments were both predicted to be pathogenic.@*CONCLUSION@#The intrachromosomal insertion of 18q21.2-q22.3 carried by the pregnant woman had probably given rise to the 18q21.2-q22.3 duplication and deletion in the two offspring. Above finding has provided a basis for genetic counseling for this pedigree.