Tang Wenting, Wu Ruohao, Meng Zhe, Li Xiaojuan, Ouyang Nengtai, Liang Liyang
Department of Research and Molecular Diagnostics, Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong 510060, China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2020 May 10;37(5):535-538. doi: 10.3760/cma.j.issn.1003-9406.2020.05.010.
To detect pathogenic variant in a juvenile with severe type Cornelia de Lange syndrome (CdLS).
A 12-year-old female presented with comprehensive developmental retardation and deformity of lower limbs. Genomic DNA was extracted from peripheral blood sample of the patient. Whole exome sequencing was performed to identify pathogenic variants. Putative variant was verified by Sanger sequencing. The impact of variants was predicted and validated by bioinformatic analysis.
A de novo missense variant, c.1507A>G (p. Lys503Glu), was found in the NIPBL gene of the proband. The variant was unreported previously and predicted to be pathogenic by PolyPhen-2, MutationTaster and SIFT. Using HomoloGene system, the 503 loci in the NIPBL protein are highly conserved. The change of amino acid (Glu), locating in 503 locus, was found to cause the Neuromodulin_N superfamily domain destroyed, resulting in severe damage to the function of NIPBL protein.
The de novo missense variant c.1507A>G (p. Lys503Glu) of the NIPBL gene probably underlies the disease in this patient.
检测一名患有重型科妮莉亚·德朗热综合征（CdLS）的青少年的致病变异。
一名12岁女性表现为全面发育迟缓及下肢畸形。从患者外周血样本中提取基因组DNA。进行全外显子组测序以鉴定致病变异。通过桑格测序验证推定的变异。通过生物信息学分析预测并验证变异的影响。
在先证者的NIPBL基因中发现一个新发错义变异，c.1507A>G（p.Lys503Glu）。该变异此前未见报道，经PolyPhen-2、MutationTaster和SIFT预测为致病。使用同源基因系统，NIPBL蛋白中的503位点高度保守。发现位于503位点的氨基酸变化（Glu）导致神经调节蛋白_N超家族结构域破坏，从而对NIPBL蛋白的功能造成严重损害。
NIPBL基因的新发错义变异c.1507A>G（p.Lys503Glu）可能是该患者疾病的病因。
