title: Is there a link between the calcium sensing receptor and Hirschsprung's disease? A mutational analysis.
abstract: BACKGROUND
  Hirschsprung's disease (HD) is a congenital malformation of the hindgut characterized by the absence of enteric ganglion cells in the submucosal and myenteric plexuses. Hirschsprung's disease is routinely treated by resection of the aganglionic bowel and pull-through procedure of the proximal ganglionated bowel to the anorectal region. Occasionally, after resection of the aganglionic bowel, HD patients still experience persistent disturbances in gut motility. The etiology of HD as well as the underlying pathomechanism for postoperative disturbances in gut motility is unclear. Molecular analysis of putative candidate genes may help to clarify the pathophysiology of these conditions. In the present study, we investigated the correlation between mutations and polymorphisms in the calcium sensing receptor (CaSR) and HD patients.
  
  
  METHODS
  Mutational screening of the CaSR coding sequence was performed via polymerase chain reaction and direct sequencing of the amplified samples from 63 HD patients and 100 controls.
  
  
  RESULTS
  We identified 3 common polymorphisms (p.A986S, p.G990R, and p.Q1011E) residing in exon 7 and 1 polymorphism in intron 5 (IVS 5-88 T>C) of the CaSR gene. Overall, 16 patients (25%) and 25 controls (25%) were carriers of the p.A986S polymorphism (P = 1). The incidence of p.R990G polymorphism of patients was twice as high as in the control group (P = .17). Furthermore, we verified a 4 times higher incidence of p.Q1011E polymorphism carriers in patients compared to the control group (P = .1).
  
  
  CONCLUSIONS
  We found a higher incidence of R990G and Q1011E polymorphisms in HD patients compared to controls. However, there was no statistically significant association between HD and the 3 polymorphic variants in the intracellular signaling region of CaSR. It will be important to further investigate genetic variations in CaSR in more patient cohorts to better characterize the function of this gene and to establish a correlation between CaSR variants and HD.
authors.affiliation: Department of Surgery, Division of Pediatric Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany. philipp.romero@med.uni-heidelberg.de
authors.forename: Philipp
authors.initials: P
authors.lastname: Romero
authors.forename: Beate
authors.initials: B
authors.lastname: Niesler
authors.forename: Hubertus
authors.initials: H
authors.lastname: Schmitz-Winnenthal
authors.forename: Guido
authors.initials: G
authors.lastname: Fitze
authors.forename: Stefan
authors.initials: S
authors.lastname: Holland-Cunz
mesh_terms: D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005819:Genetic Markers; D006627:Hirschsprung Disease / Q000235:genetics*; D006801:Humans; D007223:Infant; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D044169:Receptors, Calcium-Sensing / Q000235:genetics*
chemical_list: C095550:CASR protein, human; D005819:Genetic Markers; D044169:Receptors, Calcium-Sensing