Familial Xq27.1q28 Duplication Arising from a Maternal Interarm Forward Insertion of the X Chromosome: A Case Report

Xiang Li¹Yuan-Mei Peng²Bo-Wen Luo¹Yu-Di Luo¹Keng Feng¹De-Rong Li¹Zeng-Yu Yang¹Lingling Zhu¹Jin-Jie Pan³Ju-Jie Song³Jian Liang³Yun-Rong Qin³Wei-Wu Liu^1*Guo-Sheng Deng^1*

• ¹Reproductive Medicine Center, Maternal and Child Health Care Hospital of Yulin, Yulin, China
• ²Department of Clinical Laboratory, Yulin Red Cross Hospital, Yulin, Guangxi 537000, China, Yulin, China
• ³Department of Clinical Laboratory, Yulin Maternal and Child Health Care Hospital,, Yulin, China

Objective: This study investigates a rare case of Xq27.1q28 duplication arising from a maternal interarm forward insertion of the X chromosome, focusing on prenatal diagnosis, family analysis, and genetic counseling for a pregnant woman with repeated adverse pregnancy outcomes. Methods: Conducted in March 2023 at Yulin Maternal and Child Health Hospital, blood samples from the proband's mother , her husband, and her family, along with umbilical cord blood from the proband. G-banding chromosomal karyotyping and CNV-seq were performed and interpreted according to ACMG guidelines. The aim was to trace the origin of genetic variations and assess recurrence risks. Results: The grandmother had a 46,X,ins(X)(p22.1q27q28) karyotype; the proband's mother had a 46,X,rec(X)dup(Xq)ins(X)(p22.1q27q28)dmat karyotype; and the proband had a 46,Y,rec(X)dup(Xq)ins(X)(p22.1q27q28)mat karyotype. This indicated the proband's chromosome was inherited from the mother, originating from the grandmother. Other family members had normal karyotypes. NGS revealed a pathogenic 15.65Mb duplication in the Xq27.1-q28 region, which was present in the proband and his mother, confirming the maternal X-chromosome insertion as the cause of the duplication. Conclusion: The grandmother's chromosomal insertion in the Xq27.1q28 duplication in both the proband's mother and her offspring. Given the X-linked dominant inheritance pattern, there's a 50% recurrence risk in future offspring. Genetic counseling emphasized the importance of assisted reproductive technology (ART) for future pregnancies to mitigate the risk of recurrence.