Identification of Potential Genes in Pathogenesis and Diagnostic Value Analysis of Partial Androgen Insensitivity Syndrome Using Bioinformatics Analysis.

Yajie Peng,Hui Zhu,Huaidong Song,Xuemeng Liu,Yue Xu,Jie Qiao,Bing Han

doi:10.3389/fendo.2021.731107

Abstract

BackgroundAndrogen insensitivity syndrome (AIS) is a rare X-linked genetic disease and one of the causes of 46,XY disorder of sexual development. The unstraightforward diagnosis of AIS and the gender assignment dilemma still make a plague for this disorder due to the overlapping clinical phenotypes.MethodsPeripheral blood mononuclear cells (PBMCs) of partial AIS (PAIS) patients and healthy controls were separated, and RNA-seq was performed to investigate transcriptome variance. Then, tissue-specific gene expression, functional enrichment, and protein–protein interaction (PPI) network analyses were performed; and the key modules were identified. Finally, the RNA expression of differentially expressed genes (DEGs) of interest was validated by quantitative real-time PCR (qRT-PCR).ResultsIn our dataset, a total of 725 DEGs were captured, with functionally enriched reproduction and immune-related pathways and Gene Ontology (GO) functions. The most highly specific systems centered on hematologic/immune and reproductive/endocrine systems. We finally filtered out CCR1, PPBP, PF4, CLU, KMT2D, GP6, and SPARC by the key gene clusters of the PPI network and manual screening of tissue-specific gene expression. These genes provide novel insight into the pathogenesis of AIS in the immune system or metabolism and bring forward possible molecular markers for clinical screening. The qRT-PCR results showed a consistent trend in the expression levels of related genes between PAIS patients and healthy controls.ConclusionThe present study sheds light on the molecular mechanisms underlying the pathogenesis and progression of AIS, providing potential targets for diagnosis and future investigation.

Highlights

Androgen insensitivity syndrome (AIS; OMIM#300068), one of the common causes of 46,XY disorder/difference of sex development (DSD), is estimated to affect one in 20,000– 100,000 live births and accounts for 40%–80% of 46,XY DSD patients [1,2,3,4]
We filtered out CCR1, PPBP, PF4, CLU, KMT2D, GP6, and SPARC by the key gene clusters of the protein–protein interaction (PPI) network and manual screening of tissue-specific gene expression
This disorder is divided into three categories, ranging from complete feminization with external genitalia [complete AIS (CAIS)] to various degrees of undervirilization [partial AIS (PAIS)] and to male infertility and/or gynecomastia [mild AIS (MAIS)]

Summary

Introduction

Androgen insensitivity syndrome (AIS; OMIM#300068), one of the common causes of 46,XY disorder/difference of sex development (DSD), is estimated to affect one in 20,000– 100,000 live births and accounts for 40%–80% of 46,XY DSD patients [1,2,3,4]. Defects in AR could compromise the virilization process, exhibiting variably impaired masculinization of external genitalia, spermatogenesis arrest, gynecomastia, sparseness or absence of pubic and axillary hair, increased risk of gonadal tumors, and abnormal sex hormone levels [9] This disorder leads to abnormal symptoms of other systems in males: slightly increased height as compared with normal females, disorder of skeletal development, inherited X-linked neurodegenerative disease, increased incidence of insulin resistance and cardiovascular risk, and risk of infection and autoimmune diseases were reported in CAIS and aromatase knockout (ARKO) mice [7, 10,11,12,13]. The unstraightforward diagnosis of AIS and the gender assignment dilemma still make a plague for this disorder due to the overlapping clinical phenotypes

Methods

Results

Conclusion