Qin Jiangfeng, Zeng Yanfei, Luo Yinghua, Lu Biyu, Ya Jiaolian, Cai Pengfei, Zhang Ling, Mei Yan, Yuan Dejian, Wei Xiaoni, Xu Yuchan
Department of Medical Genetics, Liuzhou Hospital of Guangzhou Women and Children's Medical Center, Liuzhou, China.
Liuzhou Key Laboratory of Birth Defects Prevention and Control, Liuzhou Maternity and Child Healthcare Hospital, Liuzhou, China.
Cytogenet Genome Res. 2025;165(2):70-84. doi: 10.1159/000546051. Epub 2025 Apr 29.
Small supernumerary marker chromosomes (sSMCs) are small structurally abnormal chromosomes whose origin and structure are difficult to determine by conventional cytogenetic banding techniques. The aims of the study were to analyze sSMCs discovered in prenatal diagnosis, explore the origin and clinical significance of fetal sSMCs, and inform genetic counseling and reproductive health care.
Karyotyping was performed on pregnant women who underwent prenatal diagnosis in a Chinese hospital between April 2018 and April 2024. The sSMC cases encountered were further analyzed using copy number variation sequencing (CNV-seq) to determine the origin of the sSMCs and assess their clinical significance. Uniparental disomy (UPD) was excluded in the families with de novo sSMC cases using multiplex fluorescence PCR and capillary electrophoresis.
Out of 30,114 prenatal samples, 30 cases of sSMCs were identified, yielding a detection rate of 0.10%. Family analysis was performed on 23 of these cases, revealing 4 cases inherited and 19 cases of de novo aberrations. CNV-seq was conducted on 27 cases, with 14 showing no abnormalities and 13 exhibiting CNVs. Among the 10 cases where the origin of the sSMC was clearly identified, the duplications involved chromosomes 4, 10, 12, 15, 18, X, and Y, with pathogenic CNVs accounting for 70.0% (7/10) and variants of uncertain clinical significance accounting for 30.0% (3/10). Out of the 30 women with sSMCs detected, 13 chose to terminate the pregnancy, representing 43.3% (13/30). A follow-up was conducted on 13 de novo sSMC cases that were negative for CNV-seq. Among the live-born fetuses, all except one, who presented with speech delay, showed normal clinical features. UPD testing was successfully performed on 3 families (including the 3-year-old girl with speech delay), and all results were negative.
Utilizing both karyotyping and molecular genetic testing is advantageous for effectively screening and identifying sSMCs. CNV-seq is recommended as an important supplementary method for sSMC identification, thereby providing more detailed genetic counseling for prenatal diagnosis.
小额外标记染色体（sSMC）是结构异常的小染色体，其起源和结构难以通过传统细胞遗传学带型技术确定。本研究的目的是分析产前诊断中发现的sSMC，探讨胎儿sSMC的起源和临床意义，并为遗传咨询和生殖健康护理提供依据。
对2018年4月至2024年4月在中国一家医院接受产前诊断的孕妇进行核型分析。对遇到的sSMC病例进一步使用拷贝数变异测序（CNV-seq）进行分析，以确定sSMC的起源并评估其临床意义。使用多重荧光PCR和毛细管电泳在新发sSMC病例的家庭中排除单亲二体（UPD）。
在30114份产前样本中，鉴定出30例sSMC，检出率为0.10%。对其中23例进行了家系分析，发现4例为遗传，19例为新发畸变。对27例进行了CNV-seq检测，14例无异常，13例显示有CNV。在明确鉴定出sSMC起源的10例中，重复涉及4号、10号、12号、15号、18号、X和Y染色体，致病性CNV占70.0%（7/10），临床意义不确定的变异占30.0%（3/10）。在检测到sSMC的30名女性中，13名选择终止妊娠，占43.3%（13/30）。对13例CNV-seq阴性的新发sSMC病例进行了随访。在活产胎儿中，除1例有语言发育迟缓外，其他均表现正常。对3个家庭（包括1名3岁有语言发育迟缓的女孩）成功进行了UPD检测，所有结果均为阴性。
同时使用核型分析和分子遗传学检测有利于有效筛查和鉴定sSMC。建议将CNV-seq作为sSMC鉴定的重要补充方法，从而为产前诊断提供更详细的遗传咨询。
