目的: 口颌面裂 (OFC) 是常见的先天缺陷，包括唇裂, 嘴唇和口感, 和cle裂. OFC具有异质性病因, 使临床诊断复杂化，因为如果原因是Mendelian，并不总是显而易见, 环境的, 或多因素. 目前尚未针对孤立或零星的OFC进行测序; 所以, 我们估计了诊断产量 418 基因在 841 案例和 294 控件.
方法: 我们评估了 418 使用基因组测序和策划变体的基因使用美国医学遗传学标准评估其致病性.
结果: 9.04% 案件和 1.02% 控件有 “可能的致病性” 变体 (磷 < .0001), which was almost exclusively driven by heterozygous variants in autosomal genes. Cleft palate (17.6%) and cleft lip and palate (9.09%) cases had the highest yield, whereas cleft lip cases had a 2.80% yield. Out of 39 genes with likely pathogenic variants, 9 genes, including CTNND1 and IRF6, accounted for more than half of the yield (4.64% of cases). Most variants (61.8%) were "variants of uncertain significance", occurring more frequently in cases (P = .004), but no individual gene showed a significant excess of variants of uncertain significance. Conclusion: These results underscore the etiological heterogeneity of OFCs and suggest sequencing could reduce the diagnostic gap in OFCs.
布鲁斯基