Syndromic male subfertility: A network view of genome–phenome associations

Abstract

Background: Male infertility is a disorder of the reproductive system with a highly complex genetic landscape. In most cases, the reason for male infertility remains unknown; however, the importance of genetic abnormalities in the diagnosis of subfertility/infertility is becoming increasingly recognized. Several syndromes include impaired male fertility in the clinical picture, although a comprehensive analysis of genetic causes of the syndromology perspective of male reproduction is not yet available. Objectives:(1) To develop a catalog of syndromes and corresponding genes associated with impaired male fertility and (2) to visualize an up-to-date genome-phenome network of syndromic male subfertility. Materials and methods:Published literature was retrieved from the Online Mendelian Inheritance in Man, Orphanet, Human Phenotype Ontology and PubMed databases using keywords "male infertility," "syndrome," "gene," and "case report"; time period from 1980 to September, 2021. Retrieved data were organized as a catalog and complemented with identification numbers of syndromes (MIM ID) and genes (Gene ID).The genome-phenome network and the phenome network were visualized using Cytoscape and Gephi software platforms. Protein-protein interaction analysis was performed using STRING tool.Results: Retrieved syndromes were presented as (1) a catalog containing 63 syndromes and 93 associated genes, (2) a genome-phenome network including CHD7 and WT1 genes and Noonan and Kartagener syndromes, and (3) a phenome network including 63 syndromes, and 25 categories of clinical features. Discussion:The developed catalog will contribute to the advances and translational impact toward understanding the factors of syndromic male infertility. Visualized networks provide simple, flexible tools for clinicians and researchers to quickly generate hypotheses and gain a deeper understanding of underlying mechanisms affecting male reproduction.

Gonadal dysfunction in a man with Noonan syndrome from the LZTR1 variant: case report and review of literature

“…Despite the lack of evidence, female gonadal function seems not to be affected in NS. In male individuals, cryptorchidism is common, occurring in up to 80% of the cases ( 13 ), and male fertility has been reported to be decreased with oligospermia or non-obstructive azoospermia ( 14 – 16 ). Several previous studies recognized cryptorchidism as the main factor contributing to infertility ( 13 , 15 , 17 , 18 ).…”

Discovery of Drug-Responsive Phenomic Alteration-Related Driver Genes in the Treatment of Coronary Heart Disease

“…A phenomics strategy emphasizing the simultaneous study of multiple phenotypes across biological scales may be useful, particularly if the high heritability of CHD, the XYZ phenome, and its component symptoms are due to a large number of genetic variants with small effects. This strategy has been successfully applied to detect the genetic associations of the 46 CHD risk factors, 5 depression and related phenotypes, 20 neuropsychiatric disorders and cognitive impairment, 21 , 22 and different syndromes in male fertility, 23 as well as the genetic associations among psychiatric disorders, education, socioeconomic status, and brain phenome. 24 It has also been used to assess the polygenic risk score for Alzheimer’s disease in electronic health records.…”