The potential correlations between chromosomal abnormalities and craniofacial malformations (CFMs) remain a challenge in prenatal diagnosis. This study aimed to evaluate 118 fetuses with CFMs by applying chromosomal microarray analysis (CMA) and G-banded chromosome analysis. Of the 118 cases in this study, 39.8% were isolated CFMs (47/118) whereas 60.2% were non-isolated CFMs (71/118). The detection rate of chromosomal abnormalities in non-isolated CFM fetuses was significantly higher than that in isolated CFM fetuses (26/71 vs. 7/47, p = 0.01). Compared to the 16 fetuses (16/104; 15.4%) with pathogenic chromosomal abnormalities detected by karyotype analysis, CMA identified a total of 33 fetuses (33/118; 28.0%) with clinically significant findings. These 33 fetuses included cases with aneuploidy abnormalities (14/118; 11.9%), microdeletion/microduplication syndromes (9/118; 7.6%), and other pathogenic copy number variations (CNVs) only (10/118; 8.5%).We further explored the CNV/phenotype correlation and found a series of clear or suspected dosage-sensitive CFM genes including TBX1, MAPK1, PCYT1A, DLG1, LHX1, SHH, SF3B4, FOXC1, ZIC2, CREBBP, SNRPB, and CSNK2A1. These findings enrich our understanding of the potential causative CNVs and genes in CFMs. Identification of the genetic basis of CFMs contributes to our understanding of their pathogenesis and allows detailed genetic counselling.

中文翻译：

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颅面畸形胎儿染色体微阵列分析的临床应用

染色体异常和颅面畸形（CFM）之间的潜在相关性仍然是产前诊断的挑战。本研究旨在通过应用染色体微阵列分析 (CMA) 和 G 带染色体分析来评估 118 名 CFM 胎儿。在本研究的 118 例中，39.8% 是孤立的 CFM (47/118)，而 60.2% 是非孤立的 CFM (71/118)。非离体CFM胎儿染色体异常检出率显着高于离体CFM胎儿(26/71 vs. 7/47, p = 0.01)。与通过核型分析检测到的具有致病性染色体异常的 16 个胎儿（16/104；15.4%）相比，CMA 确定了具有临床显着性发现的总共 33 个胎儿（33/118；28.0%）。这 33 个胎儿包括非整倍体异常的病例（14/118；11.9%），微缺失/微复制综合征 (9/118; 7.6%) 和仅其他致病性拷贝数变异 (CNV) (10/118; 8.5%)。我们进一步探索了 CNV/表型相关性，发现了一系列明确或可疑的剂量-敏感的 CFM 基因包括 TBX1、MAPK1、PCYT1A、DLG1、LHX1、SHH、SF3B4、FOXC1、ZIC2、CREBBP、SNRPB 和 CSNK2A1。这些发现丰富了我们对 CFM 中潜在致病 CNV 和基因的理解。鉴定 CFM 的遗传基础有助于我们了解其发病机制，并允许进行详细的遗传咨询。ZIC2、CREBBP、SNRPB 和 CSNK2A1。这些发现丰富了我们对 CFM 中潜在致病 CNV 和基因的理解。鉴定 CFM 的遗传基础有助于我们了解其发病机制，并允许进行详细的遗传咨询。ZIC2、CREBBP、SNRPB 和 CSNK2A1。这些发现丰富了我们对 CFM 中潜在致病 CNV 和基因的理解。鉴定 CFM 的遗传基础有助于我们了解其发病机制，并允许进行详细的遗传咨询。