Identification of a novel missense NIPBL variant in a juvenile with severe type of Cornelia de Lange syndrome.
10.3760/cma.j.issn.1003-9406.2020.05.010
- VernacularTitle:一例重型Cornelia de Lange综合征患者的
NIPBL基因变异分析
- Author:
Wenting TANG
1
;
Ruohao WU
;
Zhe MENG
;
Xiaojuan LI
;
Nengtai OUYANG
;
Liyang LIANG
Author Information
1. Department of Research and Molecular Diagnostics, Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong 510060, China. liangliy@outlook.com.
- Publication Type:Case Reports
- MeSH:
Cell Cycle Proteins;
genetics;
Child;
De Lange Syndrome;
genetics;
Developmental Disabilities;
genetics;
Female;
Humans;
Mutation, Missense;
Phenotype
- From:
Chinese Journal of Medical Genetics
2020;37(5):535-538
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To detect pathogenic variant in a juvenile with severe type Cornelia de Lange syndrome (CdLS).
METHODS: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.
RESULTS: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.
CONCLUSION:The de novo missense variant c.1507A>G (p. Lys503Glu) of the NIPBL gene probably underlies the disease in this patient.
