Shangguan Huakun, Chen Ruimin
Department of Endocrinology, Fuzhou Children's Hospital of Fujian Medical University, Fuzhou, China.
Front Pediatr. 2022 Jul 22;10:940294. doi: 10.3389/fped.2022.940294. eCollection 2022.
Cornelia de Lange syndrome (CdLS) is a genetic disorder caused by variants in cohesion genes including , , , , and 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.
This study describes six variants of non-cohesion genes (, , and ), and assesses the reliability of 11-points scale criteria in the clinical diagnosis of CdLS.
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 variants were summarized. Clinical score comparison among patients with variants versus those with variants in non-cohesin genes was performed.
Variants in non-cohesion genes were found in six patients [ ( = 2), , , , and ]. Of them, four variants ( c.7789C > T, c.1757_1776del, c.655-1G > A, and 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 cohort, cohort, and cohort was statistically lower than those in cohort (8.92 ± 1.77 vs. 12.23 ± 2.58, 7.33 ± 2.52 vs. 12.23 ± 2.58, 5.33 ± 1.53 vs. 12.23 ± 2.58; < 0.05). The average clinical score of cohort, cohort, and cohort had not significantly different from (11 ± 2.19 vs. 12.23 ± 2.58, 10 ± 4.58 vs. 12.23 ± 2.58; > 0.05).
We described 4 novel variants of non-cohesion genes in six Chinese patients with phenotypes of CdLS. Of note, three genes (, , and ) causing features of CdLS have never been reported. The proposed clinical criteria for CdLS needed to be updated and refined, insofar as WES was necessary to confirm the diagnosis of CdLS. Our study expanded the spectra of non-cohesion genetic variations in patients with features of CdLS.
科妮莉亚·德朗热综合征（CdLS）是一种由包括 、 、 、 和 在内的黏连蛋白基因变异引起的遗传性疾病。根据2018年的共识声明，临床评分≥11分的患者可被诊断为CdLS。然而，非黏连蛋白基因而非黏连蛋白基因的一些变异也可表现为CdLS的表型。
本研究描述了非黏连蛋白基因（ 、 和 ）的6种变异，并评估11分制标准在CdLS临床诊断中的可靠性。
对6例具有CdLS特征的患者进行全外显子测序（WES）。总结了40例先前报道的由非黏连蛋白基因变异引起的具有CdLS特征的患者和34例先前报道的具有 变异的患者的表型和基因型谱。对具有 变异的患者与具有非黏连蛋白基因变异的患者进行临床评分比较。
在6例患者中发现了非黏连蛋白基因变异[ （ = 2）、 、 、 和 ]。其中，4种变异（ c.7789C > T、 c.1757_1776del、 c.655-1G > A和 c.439C > T）是新发现的。结合先前报道的病例，目前报道了46例由20种非黏连蛋白基因变异引起的具有CdLS表型的患者。在这个总队列中， 队列、 队列和 队列患者的平均临床评分在统计学上低于 队列（8.92±1.77对12.23±2.58、7.33±2.52对12.23±2.58、5.33±1.53对12.23±2.58； < 0.05）。 队列、 队列和 队列的平均临床评分与 队列无显著差异（11±2.19对12.23±2.58、10±4.58对12.23±2.58； > 0.05）。
我们描述了6例具有CdLS表型的中国患者中4种新发现的非黏连蛋白基因变异。值得注意的是，3个导致CdLS特征的基因（ 、 和 ）从未被报道过。鉴于WES对于确诊CdLS是必要的，因此提议的CdLS临床标准需要更新和完善。我们的研究扩展了具有CdLS特征患者的非黏连蛋白基因变异谱。
