Jiang Xiali, Liang Bin, Chen Bilian, Wu Xiaoqing, Wang Yan, Lin Na, Huang Hailong, Xu Liangpu
Medical Genetic Diagnosis and Therapy Center, Fujian Key Laboratory for Prenatal Diagnosis and Birth Defect, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, No. 18 Daoshan Road, Gulou District, Fuzhou City, 350001, Fujian Province, China.
Chromosome Res. 2024 Jul 19;32(3):9. doi: 10.1007/s10577-024-09754-y.
Small supernumerary marker chromosomes (sSMCs) are additional chromosomes with unclear structures and origins, and their correlations with clinical fetal phenotypes remain incompletely understood, which reduces the accuracy of genetic counseling.
We conducted a retrospective analysis of a cohort of 36 cases of sSMCs diagnosed in our center. We performed G-banding and chromosomal microarray analysis (CMA). The resulting karyotypes were compared with case reports in the literature and various databases including OMIM, DECIPHER, ClinVar, ClinGen, ISCA, DGV, and PubMed.
Karyotype analysis data revealed that 19 out of 36 fetuses were mosaic. Copy number variants (CNVs) analysis results showed that 27 out of 36 fetuses harbored pathogenic/likely pathogenic variants. Among these 27 cases, 11 fetuses carried sex chromosome-related CNVs, including 4 female cases exhibiting Turner syndrome phenotypes and 7 cases showing Y chromosome deletions. In the remaining 16 fetuses with autosomal CNVs, 9 fetuses carried variants associated with Cat eye syndrome, Emanuel syndrome, Tetrasomy 18p, and 15q11-q13 duplication syndrome. Among these, 22 fetuses were terminated, and the remaining 5 fetuses were delivered and developed normally. Additionally, we identified a few variants with unclear pathogenicity.
Cytogenetic analysis is essential for identifying the pathogenicity of sSMCs and increasing the accuracy of genetic counseling.
小额外标记染色体（sSMC）是结构和起源不明的额外染色体，其与临床胎儿表型的相关性仍未完全明确，这降低了遗传咨询的准确性。
我们对本中心诊断的36例sSMC病例进行了回顾性分析。我们进行了G显带和染色体微阵列分析（CMA）。将所得核型与文献及包括OMIM、DECIPHER、ClinVar、ClinGen、ISCA、DGV和PubMed在内的各种数据库中的病例报告进行比较。
核型分析数据显示，36例胎儿中有19例为嵌合体。拷贝数变异（CNV）分析结果显示，36例胎儿中有27例携带致病性/可能致病性变异。在这27例中，11例胎儿携带与性染色体相关的CNV，包括4例表现为特纳综合征表型的女性病例和7例Y染色体缺失病例。在其余16例携带常染色体CNV的胎儿中，9例胎儿携带与猫眼综合征、 Emanuel综合征、18号染色体短臂四体和15q11 - q13重复综合征相关的变异。其中，22例胎儿终止妊娠，其余5例胎儿正常分娩并发育。此外，我们还发现了一些致病性不明的变异。
细胞遗传学分析对于确定sSMC的致病性和提高遗传咨询的准确性至关重要。
