title: Functional analyses of RET mutations in Chinese Hirschsprung disease patients.
abstract: BACKGROUND
  Hirschsprung disease (HSCR) is a congenital disease characterized by the absence of ganglion cells in various length of distal digestive tract. The rearranged during transfection gene (RET) is considered the major gene in HSCR. Although an increasing number of HSCR-associated RET coding sequence (CDS) mutations have been identified in recent years, not many have been investigated for functional consequence on the RET protein.
  
  
  RESULTS
  We examined the functional implications of the de novo RET-CDS mutations V145G, Y483X, V636fsX1, and F961L that we first identified in sporadic Chinese patients with HSCR. The V145G disrupted RET glycosylation and F961L RET phosphorylation. Presumably, the truncation mutations would affect the translocation or the anchoring of the RET protein onto the cellular membrane.
  
  
  CONCLUSIONS
  The study of RET-CDS mutations that appear de novo is essential not only for understanding the mechanistic of the disease but also for penetrance and recurrence risk estimations, being the ultimate goal for the improvement in disease management and counseling.
authors: Division of Paediatric Surgery, Department of Surgery, The University of Hong Kong, Hong Kong, Special Administrative Region, China.
authors: Thomas Y Y
authors: TY
authors: Leon
authors: Man-Ting
authors: MT
authors: So
authors: Vincent C H
authors: VC
authors: Lui
authors: Robert M W
authors: RM
authors: Hofstra
authors: Paul K H
authors: PK
authors: Tam
authors: Elly S W
authors: ES
authors: Ngan
authors: Maria-Mercè
authors: MM
authors: Garcia-Barceló
mesh_terms: D044466:Asian People / Q000235:genetics*; D045744:Cell Line, Tumor; D005260:Female; D006627:Hirschsprung Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D019683:Penetrance; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics* / Q000378:metabolism*
chemical_list: D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human