TY - JOUR AB - Endometriosis is an enigmatic condition with an unknown etiology and a poorly understood pathogenesis. It is considered to appear from the interplay of many genetic and environmental factors, affecting up to 10% of women and represents a major cause of pain and infertility. The familial association of endometriosis, as demonstrated through monozygotic twin and family studies suggests a genetic contribution to the disease, with further case‑control and genome‑wide association studies (GWAS) detecting various endometriosis risk factors. In a recent study, we described a unique, three‑generation family of Cretan origin (Greece) with 7 females with surgically confirmed endometriosis (grandmother, 3 daughters and 3 granddaughters). All the affected members of this family displayed a variety of clinical manifestations and complications. In the present study, to further analyze the genetic variants conferring the risk of developing endometriosis, whole exome sequencing (WES) was performed, using the AmpliSeq technology on the Ion Proton platform. An initial analysis of 64 variants that were detected across the 14 genes previously confirmed to be associated with endometriosis, did not identify any deleterious exonic variants in these genes. However, further analysis revealed 2 hemizygous deletions in the grandmother that segregate in several of her affected offspring. The first deletion was found in the UGT2B28 locus, spanning 7 informative sequence variants across at least 14 kb. The second deletion, located in USP17L2, spans 3 informative variants across at least 2 kb. On the whole, the findings of the presents study implicate 2 additional genes in the pathogenesis of endometriosis, apart from those already identified by GWAS. AD - Juneau Biosciences, LLC, Salt Lake City, UT, USA 3rd Department of Obstetrics and Gynecology, Aristotle University of Thessaloniki, Thessaloniki 541 24, Greece Section of Molecular Pathology and Human Genetics, Department of Internal Medicine, University of Crete, Heraklion 710 03, Crete, Greece Department of Obstetrics and Gynecology, Venizeleio General Hospital of Heraklion, Heraklion 714 09, Greece Laboratory of Clinical Virology, Medical School, University of Crete, Heraklion 710 03, Crete, Greece AU - Albertsen,Hans,M. AU - Matalliotaki,Charoula AU - Matalliotakis,Michail AU - Zervou,Maria,I. AU - Matalliotakis,Ioannis AU - Spandidos,Demetrios,A. AU - Chettier,Rakesh AU - Ward,Kenneth AU - Goulielmos,George,N. DA - 2019/03/01 DO - 10.3892/mmr.2019.9818 EP - 1720 IS - 3 JO - Mol Med Rep KW - endometriosis gene variants whole exome sequencing family history PY - 2019 SN - 1791-2997 1791-3004 SP - 1716 ST - Whole exome sequencing identifies hemizygous deletions in the UGT2B28 and USP17L2 genes in a three‑generation family with endometriosis T2 - Molecular Medicine Reports TI - Whole exome sequencing identifies hemizygous deletions in the UGT2B28 and USP17L2 genes in a three‑generation family with endometriosis UR - https://doi.org/10.3892/mmr.2019.9818 VL - 19 ER -