Winerdal Max, Westenius Eini, Granfors Michaela, Pettersson Maria, Iwarsson Erik
Department of Clinical Genetics, L4:03, Karolinska University Laboratory, Karolinska University Hospital, 171 76, Stockholm, Sweden.
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
Mol Cytogenet. 2020 Dec 17;13(1):51. doi: 10.1186/s13039-020-00520-3.
Small copy number variations confined to the placenta are extremely rare findings in chorionic villus sampling, nonetheless of great clinical importance. To the best of our knowledge, this is the first reported case of confined placental mosaicism for an intragenic Duchenne muscular dystrophy (DMD) gene deletion.
We describe a pregnant woman where confined placental mosaicism for an intragenic DMD deletion was detected. She was referred for a chorionic villus sampling due to an increased risk of trisomy 21 derived from combined first trimester screening. Rapid aneuploidy detection showed a male fetus with normal results for chromosomes 13, 18 and 21. A chromosomal microarray demonstrated a deletion of exons 61-62 in the DMD gene in approximately 50% of the cells. A follow-up analysis on amniotic cells showed a normal result for the DMD gene. Hence, confined placental mosaicism was confirmed.
We propose tissue specific fragile sites as a possible theoretical mechanism for the formation of submicroscopic copy number variations and highlight that the finding of DMD deletion mosaicism in a chorionic villus sample might be isolated to the placenta. Therefore, confirmation by amniocentesis is of crucial clinical importance to avoid misdiagnosis of the fetus.
局限于胎盘的小拷贝数变异在绒毛取样中是极其罕见的发现，但具有重要的临床意义。据我们所知，这是首例关于基因内杜氏肌营养不良（DMD）基因缺失的局限胎盘嵌合体的报道病例。
我们描述了一名孕妇，在其体内检测到了基因内DMD缺失的局限胎盘嵌合体。由于孕早期联合筛查提示21三体综合征风险增加，她被转诊进行绒毛取样。快速非整倍体检测显示胎儿为男性，13、18和21号染色体结果正常。染色体微阵列分析显示，约50%的细胞中DMD基因的外显子61 - 62缺失。对羊水细胞的后续分析显示DMD基因结果正常。因此，证实了局限胎盘嵌合体的存在。
我们提出组织特异性脆性位点可能是亚微观拷贝数变异形成的一种理论机制，并强调在绒毛取样中发现的DMD缺失嵌合体可能仅局限于胎盘。因此，通过羊膜穿刺术进行确认对于避免胎儿误诊具有至关重要的临床意义。
