Mónica Aguinaga1, Maryam Rezaei2, Irma Monroy3, Nawel Mechtouf2, Javier Pérez3, Elsa Moreno4, Yolotzin Valdespino4, Carolina Galaz5, Guadalupe Razo3, Daniela Medina3, Raúl Piña6, Rima Slim7. 1. Department of Genetics and Human Genomics, Instituto Nacional de Perinatología, Montes Urales 800 Col. Lomas Virreyes, 11000, Mexico City, Mexico. aguinagamonica09@gmail.com. 2. Department of Human Genetics, McGill University, Montreal, Quebec, Canada. 3. Department of Genetics and Human Genomics, Instituto Nacional de Perinatología, Montes Urales 800 Col. Lomas Virreyes, 11000, Mexico City, Mexico. 4. Department of Pathology, Instituto Nacional de Perinatología, Mexico City, Mexico. 5. Académico tiempo completo en la Escuela de Ciencias de la Salud, Universidad del Valle de México, Campus Noroeste, Mexico City, Mexico. 6. Instituto de Ciencias en Reproducción Humana (Instituto Vida), León, Guanajuato, Mexico. 7. Departments of Human Genetics and Obstetrics and Gynecology, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
Abstract
PURPOSE: To investigate the frequency of a founder mutation in NLRP7, L750V, in independent cohorts of Mexican patients with recurrent hydatidiform moles (RHMs). METHODS: Mutation analysis was performed by Sanger sequencing on DNA from 44 unrelated Mexican patients with RHMs and seven molar tissues from seven additional unrelated patients. RESULTS: L750V was present in homozygous or heterozygous state in 37 (86%) patients and was transmitted on the same haplotype to patients from different states of Mexico. We also identified a second founder mutation, c.2810+2T>G in eight (18.1%) patients, and a novel premature stop-codon mutation W653*. CONCLUSION: Our data confirm the strong founder effect for L750V, which appears to be the most common mutation in NLRP7. We also report on six healthy live births to five patients with biallelic NLRP7 mutations, two from spontaneous conceptions and four from donated ovum and discuss our recommendations for DNA testing and genetic counseling.
PURPOSE: To investigate the frequency of a founder mutation in NLRP7, L750V, in independent cohorts of Mexican patients with recurrent hydatidiform moles (RHMs). METHODS: Mutation analysis was performed by Sanger sequencing on DNA from 44 unrelated Mexican patients with RHMs and seven molar tissues from seven additional unrelated patients. RESULTS: L750V was present in homozygous or heterozygous state in 37 (86%) patients and was transmitted on the same haplotype to patients from different states of Mexico. We also identified a second founder mutation, c.2810+2T>G in eight (18.1%) patients, and a novel premature stop-codon mutation W653*. CONCLUSION: Our data confirm the strong founder effect for L750V, which appears to be the most common mutation in NLRP7. We also report on six healthy live births to five patients with biallelic NLRP7 mutations, two from spontaneous conceptions and four from donated ovum and discuss our recommendations for DNA testing and genetic counseling.
Authors: Rosemary A Fisher; Stuart A Lavery; Anna Carby; Shadi Abu-Hayyeh; Rebecca Swingler; Neil J Sebire; Michael J Seckl Journal: Lancet Date: 2011-11-28 Impact factor: 79.321