目的:我们提出了在妊娠羊膜腔穿刺术中使用正常整倍体细胞系进行15q11.2微复制的镶嵌性,具有良好的胎儿结局,并且具有微复制的非整倍体细胞系在出生后减少。
方法:35岁,由于母亲年龄高,初产妇在妊娠17周时接受了羊膜穿刺术。羊膜穿刺术显示核型为46,XY。对从未培养的羊膜细胞提取的DNA进行的同时阵列比较基因组杂交(aCGH)分析显示,15q11.2微重复的镶嵌率为33.76%。她被推荐接受遗传咨询。在妊娠23周时重复进行羊膜穿刺术,核型为46,XY。从未培养的羊膜细胞中提取的DNA的同时aCGH分析显示了arr[GRCh37(hg19)]15q11.2(23,889,686-25,514,125)×2.45的结果,与马赛克1.624-Mb微重复一致,马赛克水平为40%-45%(对数2比率=0.28),包含MEL2,NDN的9个OMIM基因,PWRN2、PWRN1、NPAP1、SNRPN、SNHG14、SNORD116-1和SNORD115-1。对100个未培养的羊膜细胞进行间期荧光原位杂交(FISH)分析,在19个细胞中检测到15q11.2重复,与19%(19/100细胞)镶嵌15q11.2重复一致。多态性DNA标记分析排除单亲二体(UPD)15。产前超声检查结果无明显变化。建议她继续怀孕,接生了一个3865克表型正常的男婴。aCGH对出生时从脐带血提取的DNA和四个月大时的颊粘膜细胞进行分析,发现arr(1-22)×2,X×1,Y×1,并且在所有样本中均未检测到基因组失衡。4月龄的104个颊粘膜细胞的间期FISH分析检测到4个细胞(4/104=4%),具有15q11.2重复,与正常对照组的0%(0/102个细胞)相比。新生儿发育正常。
结论:羊膜穿刺术中使用正常整倍体细胞系进行15q11.2微复制的镶嵌可能是一种良性疾病,并与有利的胎儿结局和出生后减少具有微复制的非整倍体细胞系有关。
OBJECTIVE: We present mosaicism for a 15q11.2 microduplication with a normal euploid cell line at amniocentesis in a pregnancy with a favorable fetal outcome and postnatal decrease of the aneuploid cell line with the microduplication.
METHODS: A 35-year-old, primigravid woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 46,XY. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed 33.76% mosaicism for a 15q11.2 microduplication. She was referred for genetic counseling. Repeat amniocentesis was performed at 23 weeks of gestation, and the karyotype was 46,XY. Simultaneous aCGH analysis on the DNA extracted from uncultured amniocytes revealed the result of arr [GRCh37 (hg19)] 15q11.2 (23, 889, 686-25,514,125) × 2.45, consistent with a mosaic 1.624-Mb microduplication with the mosaic level of 40%-45% (log2 ratio = 0.28) encompassing nine OMIM genes of MAGEL2, NDN, PWRN2, PWRN1, NPAP1, SNRPN, SNHG14, SNORD116-1 and SNORD115-1. Interphase fluorescence in situ hybridization (FISH) analysis on 100 uncultured amniocytes detected a 15q11.2 duplication in 19 cells, consistent with 19% (19/100 cells) mosaic15q11.2 duplication. Polymorphic DNA marker analysis excluded uniparental disomy (UPD) 15. Prenatal ultrasound findings were unremarkable. She was advised to continue the pregnancy, and a 3865-g phenotypically normal male baby was delivered. aCGH analysis on the DNA extracted from cord blood at birth and buccal mucosal cells at age four months revealed arr (1-22) × 2, X × 1, Y × 1 and detected no genomic imbalance in all samples. Interphase FISH analysis on 104 buccal mucosal cells at age four months detected four cells (4/104 = 4%) with a 15q11.2 duplication, compared with 0% (0/102 cells) in the normal control. The neonate was normal in the development.
CONCLUSIONS: Mosaicism for a 15q11.2 microduplication at amniocentesis with a normal euploid cell line can be a benign condition and associated with a favorable fetal outcome and postnatal decrease of the aneuploid cell line with the microduplication.