Association study of PTPN11 gene rs121918457 mutation and rs12425405 polymorphism in Noonan syndrome and related diseases
10.3760/cma.j.cn141217-20240910-00267
- VernacularTitle:PTPN11基因多态性与努南综合征及其他疾病表型的关联研究
- Author:
Juan DU
1
;
Bing ZHANG
1
;
He LI
1
;
Zibo ZHANG
1
;
Li LIU
1
Author Information
1. 天津市儿童医院免疫综合内科，天津 300070
- Publication Type:Journal Article
- Keywords:
Noonan syndrome;
Genetic association study;
Cardiovascular diseases;
Autoimmunity
- From:
Chinese Journal of Rheumatology
2025;29(5):387-392
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the role of PTPN11 gene polymorphisms in Noonan syndrome (NS) and other related diseases and to evaluate the association between PTPN11 gene variants and various disease phenotypes.Methods:This study first described a case of 7-year-old girl diagnosed with Nonan symdrome who visited our department in Februay 2024 presented to our department six months ago and was diagnosed with Noonan syndrome. Whole-exome sequencing revealed a heterozygous variant in her PTPN11 gene, with the single nucleotide polymorphism (SNP) locus identified as rs121918457. Due to limited phenotypic data associated with rs121918457 in available databases, the cis-expression quantitative trait locus (cis-eQTL) rs12425405, located near the PTPN11 gene, was used as a proxy to further investigate the impact of PTPN11 gene expression regulation on various disease phenotypes. A PheWAS analysis was conducted to assess the statistical association between PTPN11 polymorphism and diverse phenotypic traits. All data were analyzed using the PheWeb online tool, and statistical significance was tested using the P-value. Bonferroni correction was applied for multiple comparisons to ensure the reliability of the results. The significance level was set at P<0.05, and the Bonferroni-corrected significance threshold was P=3.52×10 -5. Results:This case demonstrated that, in addition to the typical clinical features of Noonan syndrome, the child also presented with significant hypertension and autoimmune symptoms (such as joint pain, peripheral nerve damage, and positive antinuclear antibodies). The PheWAS analysis revealed significant statistical associations between the rs12425405 polymorphism and the following disease phenotypes: myocardial infarction ( P=1.90×10 -5), coronary atherosclerosis ( P=7.40×10 -5), ischemic heart disease ( P=2.30×10 -5), and hypertension ( P=8.8×10 -5). Additionally, rs12425405 showed statistical associations with some autoimmune symptoms (such as rheumatoid arthritis) ( P=0.027), but did not reach the corrected significance threshold ( P>3.52×10 -5). Conclusion:PTPN11 gene mutations are not only pathogenic factors in Noonan syndrome but may also play a critical role in the development of cardiovascular diseases and are associated with autoimmune symptoms. However, further research is needed to elucidate the functional mechanisms of the PTPN11 gene across multiple diseases and determine whether common genetic drivers are present.
