Phenotypes of Cornelia de Lange syndrome caused by non-cohesion genes: Novel variants and literature review

作者：Huakun Shangguan, Ruimin Chen · 发表于：Frontiers in Pediatrics · 年份：2022 · DOI：10.3389/fped.2022.940294 · 被引用次数：13 · 研究领域：Genomics and Chromatin Dynamics、RNA Research and Splicing、Cancer-related gene regulation

Background Cornelia de Lange syndrome (CdLS) is a genetic disorder caused by variants in cohesion genes including NIPBL , SMC1A , SMC3 , RAD21 , and HDAC8. According to the 2018 consensus statement, a patient with clinical scored ≥ 11 points could be diagnosed as CdLS. However, some variants in non-cohesion genes rather than cohesion genes can manifest as phenotypes of CdLS. Objectives This study describes six variants of non-cohesion genes ( KDM6A , KMT2D, KMT2A ANKRD11 , and UBE2A ), and assesses the reliability of 11-points scale criteria in the clinical diagnosis of CdLS. Methods Whole-exome sequencing (WES) was performed on six patients with features of CdLS. Phenotypic and genotypic spectra of 40 previously reported patients with features of CdLS caused by non-cohesion genes variants and 34 previously reported patients with NIPBL variants were summarized. Clinical score comparison among patients with NIPBL variants versus those with variants in non-cohesin genes was performed. Results Variants in non-cohesion genes were found in six patients [ KMT2A ( n = 2), KMT2D , ANKRD11 , KDM6A , and UBE2A ]. Of them, four variants ( KMT2A c.7789C > T, ANKRD11 c.1757_1776del, KDM6A c.655-1G > A, and UBE2A c.439C > T) were novel. Combining with previously reported cases, 46 patients with phenotypes of CdLS caused by variants in 20 non-cohesion genes are now reported. From this total cohort, the average clinical score of patients in ANKRD11 cohort, SETD5 cohort, ...