Defining the phenotype-genotype correlation of small supernumerary marker chromosomes (sSMCs) remains a challenge in prenatal diagnosis. We karyotyped 20,481 amniotic fluid samples from pregnant women and explored the molecular characteristics of sSMCs using a single nucleotide polymorphism (SNP) array. Out of the 20,481 samples, 15 abnormal karyotypes with sSMC were detected (frequency: 0.073%) and the chromosomal origin was successfully identified by SNP array in 14 of them. The origin of sSMCs were mainly acrocentric-derived chromosomes and the Y chromosome. Two cases of sSMC combined with uniparental disomy (UPD) were detected, UPD(1) and UPD(22). More than half of the cases of sSMC involved mosaicism (8/15) and pathogenicity (9/15) in prenatal diagnosis. A higher prevalence of mosaicism for non-acrocentric chromosomes than acrocentric chromosomes was also revealed. One sSMC derived from chromosome 3 with a neocentromere revealed a 24.99-Mb pathogenic gain of the 3q26.31q29 region on the SNP array, which presented as an abnormal ultrasound indicating nasal bone hypoplasia. The clinical phenotypes of sSMCs are variable and so further genetic testing and parental karyotype analysis are needed to confirm the characteristics of sSMCs. The SNP array used here allows a detailed characterisation of the sSMC and establishes a stronger genotype-phenotype correlation, thus allowing detailed genetic counselling for prenatal diagnosis.

中文翻译：

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使用单核苷酸多态性阵列对小的多余标记染色体进行分子描绘。

定义小的多余标记染色体 (sSMC) 的表型-基因型相关性仍然是产前诊断的挑战。我们对来自孕妇的 20,481 份羊水样本进行了核型分析，并使用单核苷酸多态性 (SNP) 阵列探索了 sSMC 的分子特征。在20,481份样本中，检出15份sSMC异常核型（频率：0.073%），其中14份通过SNP芯片成功鉴定了染色体来源。sSMCs的起源主要是近端着丝粒染色体和Y染色体。检测到两例 sSMC 合并单亲二体 (UPD)，UPD(1) 和 UPD(22)。超过一半的 sSMC 病例在产前诊断中涉及嵌合体 (8/15) 和致病性 (9/15)。还揭示了非近端着丝粒染色体的镶嵌现象比近端着丝粒染色体更高。一个来自 3 号染色体的具有新着丝粒的 sSMC 显示 SNP 阵列上 3q26.31q29 区域的致病性增益为 24.99-Mb，表现为异常超声，表明鼻骨发育不全。sSMCs 的临床表型是多变的，因此需要进一步的基因检测和亲本核型分析来确认 sSMCs 的特征。此处使用的 SNP 阵列允许对 sSMC 进行详细表征，并建立更强的基因型-表型相关性，从而为产前诊断提供详细的遗传咨询。其表现为异常超声，表明鼻骨发育不全。sSMCs 的临床表型是多变的，因此需要进一步的基因检测和亲本核型分析来确认 sSMCs 的特征。此处使用的 SNP 阵列允许对 sSMC 进行详细表征，并建立更强的基因型-表型相关性，从而为产前诊断提供详细的遗传咨询。其表现为异常超声，表明鼻骨发育不全。sSMCs 的临床表型是多变的，因此需要进一步的基因检测和亲本核型分析来确认 sSMCs 的特征。此处使用的 SNP 阵列允许对 sSMC 进行详细表征，并建立更强的基因型-表型相关性，从而为产前诊断提供详细的遗传咨询。