Polyorchidism is a rare congenital disorder defined as the presence of more than two testicles for which the underlying etiology is unknown. Prior research in this laboratory suggested a new anatomical-functional description for polyorchidism of Type 3 Subgroup B, or supernumerary testis (SNT) attached to the draining epididymis and vas deferens without reproductive potential and SNT located outside the scrotal sac. The purpose of the current investigation was to examine the mechanism underlying the role(s) of cadherins and catenins in the development of polyorchidism using genomic analysis of a cadaveric polyorchid. Formyl Fix Paraffin Embedded tissue samples of a SNT from a 96-year-old polyorchid were prepared using the Accel-NGS 2S Plus DNA Library Kit for whole exome sequencing (Integrated DNA Technology, Coralville, IA). Paired end sequencing was carried out using the Illumina NovaSeq 6000 system (Illumina, San Diego, CA) using 150 bp reads to an average depth of coverage of 44x. BLAST was used to analyze and compare the SNT sequence to reference genomes in the NCBI database. Sequence analysis of the SNT showed two missense mutations that resulted in single nucleotide variants (SNV) within exons of the N-Cadherin gene (CHD2), NT 23, T to C (Leu 8 to Pro) and NT 2441, A to G (Asn 845 to Ser), respectively. A mutation in the Desmocollin 2 (DSC2) gene was also demonstrated; NT 2393, G to A. The present research suggests a novel biomolecular mechanism based on N-Cad and p120 catenin underlying the development of polyorchidism with application to supernumerary organs in other systems and to metastasis of neoplasms.
Jack D. Walsh1A, Ernest F. Talarico, Jr.2B,3C, Joseph G. Castaneda3C, Sana M. Wahab3C, Katelyn M. Paulus3C, Amy E. Stromberg3C, Victoria N. Olson3C, Griffin D. Hall4D, Paul J. Janus3C, Nicholas R. Rocco5E
1 Department of Chemistry, 2 Department of Anatomy, 3 Department of Biology, 4 College of Pharmacy, 5 Department of Urology
A Georgia Institute of Technology, Atlanta, Georgia, USA
B Tan Tao University School of Medicine, Long An Province, Việt Nam
C North Park University, Chicago, Illinois, USA
D Roosevelt University, Chicago, Illinois, USA
E United States Naval Hospital Guam, Agana Heights, Guam, USA