germline mutation in nlrp2 (nalp2) in a familial imprinting disorder (beckwith-wiedemann syndrome)生殖系突变nlrp2(nalp2)家族印迹障碍(贝威二氏综合征).pdfVIP

Germline Mutation in NLRP2 (NALP2) in a Familial Imprinting Disorder (Beckwith-Wiedemann Syndrome) 1 1,2 1 1 1 3,4,5 Esther Meyer , Derek Lim , Shanaz Pasha , Louise J. Tee , Fatimah Rahman , John R. W. Yates , C. Geoffrey Woods3,4,5, Wolf Reik6,7, Eamonn R. Maher1,2* 1 Department of Medical and Molecular Genetics, Institute of Biomedical Research, University of Birmingham, Birmingham, United Kingdom, 2 West Midlands Regional Genetics Service, Birmingham Women’s Hospital, Edgbaston, Birmingham, United Kingdom, 3 Department of Medical Genetics, University of Cambridge, Cambridge, United Kingdom, 4 Institute for Medical Research, Addenbrooke’s Hospital, Cambridge, United Kingdom, 5 East Anglian Medical Genetics Service, Addenbrooke’s Treatment Centre, Addenbrooke’s Hospital, Cambridge, United Kingdom, 6 Laboratory of Developmental Genetics and Imprinting, The Babraham Institute, Cambridge, United Kingdom, 7 Centre for Trophoblast Research, University of Cambridge, Cambridge, United Kingdom Abstract Beckwith-Wiedemann syndrome (BWS) is a fetal overgrowth and human imprinting disorder resulting from the deregulation of a number of genes, including IGF2 and CDKN1C, in the imprinted gene cluster on chromosome 11p15.5. Most cases are sporadic and result from epimutations at either of the two 11p15.5 imprinting centres (IC1 and IC2). However, rare familial cases may be associated with germline 11p15.5 deletions causing abnormal imprinting in cis. We report a family with BWS and an IC2 epimutation in which affected siblings had inherited different parental 11p15.5 alleles excluding an in cis mechanism. Using a positional-candidate gene approach, we found that the m