comprehensive analysis of nrg1 common and rare variants in hirschsprung patients综合分析nrg1常见和罕见变异巨结肠患者.pdf

Comprehensive Analysis of NRG1 Common and Rare Variants in Hirschsprung Patients ´ 1,2 1,2 ´ ´ ˜ 1,2 ´ 1,2 Berta Luzon-Toro , Ana Torroglosa , Rocıo Nunez-Torres , Marıa Valle Enguix-Riego , Raquel ´ ´ 1,2 ´ 3 ˜ 1,2 1,2 Marıa Fernandez , Juan Carlos de Agustın , Guillermo Antinolo , Salud Borrego * ´ 1 Department of Genetics, Reproduction and Fetal Medicine. Institute of Biomedicine of Seville (IBIS), University Hospital Virgen del Rocıo/CSIC/University of Seville, ´ Seville, Spain, 2 Centre for Biomedical Network Research on Rare Diseases (CIBERER), Seville, Spain, 3 Department of Pediatric Surgery, University Hospital Virgen del Rocıo, Seville, Spain Abstract Hirschsprung disease (HSCR, OMIM 142623) is a developmental disorder characterized by the absence of ganglion cells along variable lengths of the distal gastrointestinal tract, which results in tonic contraction of the aganglionic gut segment and functional intestinal obstruction. The RET proto-oncogene is the major gene for HSCR with differential contributions of its rare and common, coding and noncoding mutations to the multifactorial nature of this pathology. Many other genes have been described to be associated with the pathology, as NRG1 ge