Julio Martin1, Yuting Yi2, Trinidad Alberola3, Beatriz Rodríguez-Iglesias3, Jorge Jiménez-Almazán3, Qin Li4, Huiqian Du2, Pilar Alama5, Amparo Ruiz5, Ernesto Bosch5, Nicolas Garrido4, Carlos Simon6. 1. IGenomix, Parc Cientific Univeristat Valencia, Valencia, Spain. Electronic address: julio.martin@igenomix.com. 2. Binhai Genomics Institute and Tianjin Translational Genomics Center, BGI-Tianjin, Tianjin, People's Republic of China. 3. IGenomix, Parc Cientific Univeristat Valencia, Valencia, Spain. 4. BGI-Shenzen, Shenzhen, People's Republic of China. 5. Instituto Valenciano de Infertilidad Valencia and Fundación Instituto Valenciano de Infertilidad, Valencia, Spain. 6. IGenomix, Parc Cientific Univeristat Valencia, Valencia, Spain; Instituto Valenciano de Infertilidad Valencia and Fundación Instituto Valenciano de Infertilidad, Valencia, Spain; Department of Obstetrics and Gynecology, Valencia University, Instituto Universitario IVI/INCLIVA, Valencia, Spain.
Abstract
OBJECTIVE: To develop an expanded pan-ethnic preconception carrier genetic screening test for use in assisted reproductive technology (ART) patients and donors. DESIGN: Retrospective analysis of results obtained from 2,570 analyses. SETTING: Reproductive genetic laboratory. PATIENT(S): The 2,570 samples comprised 1,170 individuals from the gamete donor programs; 1,124 individuals corresponding to the partner of the patient receiving the donated gamete; and 276 individuals from 138 couples seeking ART using their own gametes. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Next-generation sequencing of 549 recessive and X-linked genes involved in severe childhood phenotypes reinforced with five complementary tests covering high prevalent mutations not detected by next-generation sequencing. RESULT(S): Preclinical validation included 48 DNA samples carrying known mutations for 27 genes, resulting in a sensitivity of 99%. In the clinical dataset, 2,161 samples (84%) tested positive, with an average carrier burden of 2.3 per sample. Five percent of the couples using their own gametes were found to have pathogenic variants conferring high risk for six different diseases. These high-risk couples and patients received genetic counseling and recommendations for preimplantation genetic diagnosis. For patients receiving gamete donation, we applied a genetic testing and blinded matching system to avoid high-risk combinations regardless of their carrier burden. For female donors, 1.94% were positive for X-linked conditions; they received genetic counselling and were discarded. CONCLUSION(S): We have developed a comprehensive carrier genetic screening test that, combined with our matching system and genetic counseling, constitutes a powerful tool to avoid more than 600 mendelian diseases in the offspring of patients undergoing ART.
OBJECTIVE: To develop an expanded pan-ethnic preconception carrier genetic screening test for use in assisted reproductive technology (ART) patients and donors. DESIGN: Retrospective analysis of results obtained from 2,570 analyses. SETTING: Reproductive genetic laboratory. PATIENT(S): The 2,570 samples comprised 1,170 individuals from the gamete donor programs; 1,124 individuals corresponding to the partner of the patient receiving the donated gamete; and 276 individuals from 138 couples seeking ART using their own gametes. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Next-generation sequencing of 549 recessive and X-linked genes involved in severe childhood phenotypes reinforced with five complementary tests covering high prevalent mutations not detected by next-generation sequencing. RESULT(S): Preclinical validation included 48 DNA samples carrying known mutations for 27 genes, resulting in a sensitivity of 99%. In the clinical dataset, 2,161 samples (84%) tested positive, with an average carrier burden of 2.3 per sample. Five percent of the couples using their own gametes were found to have pathogenic variants conferring high risk for six different diseases. These high-risk couples and patients received genetic counseling and recommendations for preimplantation genetic diagnosis. For patients receiving gamete donation, we applied a genetic testing and blinded matching system to avoid high-risk combinations regardless of their carrier burden. For female donors, 1.94% were positive for X-linked conditions; they received genetic counselling and were discarded. CONCLUSION(S): We have developed a comprehensive carrier genetic screening test that, combined with our matching system and genetic counseling, constitutes a powerful tool to avoid more than 600 mendelian diseases in the offspring of patients undergoing ART.
Authors: Marta Molina Romero; Alberto Yoldi Chaure; Miguel Gañán Parra; Purificación Navas Bastida; José Luis Del Pico Sánchez; Ángel Vaquero Argüelles; Paloma de la Fuente Vaquero; Juan Pablo Ramírez López; José Antonio Castilla Alcalá Journal: J Assist Reprod Genet Date: 2022-01-29 Impact factor: 3.412
Authors: Jason M Franasiak; Meir Olcha; Paul A Bergh; Kathleen H Hong; Marie D Werner; Eric J Forman; Rebekah S Zimmerman; Richard T Scott Journal: Genet Med Date: 2016-03-03 Impact factor: 8.822