Idiopathic slow-transit constipation is not associated with mutations of the RET proto-oncogene or GDNF.
OBJECTIVE
Idiopathic slow-transit constipation is a severe disorder of unknown cause. The onset in early childhood and history of constipation or Hirschsprung's disease in close family relatives suggest that slow-transit constipation could have a genetic basis. Several germline mutations have been described in Hirschsprung's disease, including mutations of RET and the gene encoding its ligand glial cell-derived neurotrophic factor. The aim of this study was to screen a panel of 16 cases of familial idiopathic slow-transit constipation, including 4 families in which there were relatives with Hirschsprung's disease, for RET and glial cell-derived neurotrophic factor mutations previously identified in Hirschsprung's disease.


METHODS
Genomic DNA from 16 patients with slow-transit constipation and four relatives with Hirschsprung's disease was analyzed using single strand and heteroduplex conformation polymorphism analysis at two conditions and by direct DNA sequencing using the fluorescent dideoxy terminator method.


RESULTS
Although common sequence polymorphisms were demonstrated with a frequency comparable with published data, no published or new mutation was seen in any of the exons of RET or glial cell-derived neurotrophic factor.


CONCLUSIONS
Mutation of RET or glial cell-derived neurotrophic factor is not a frequent cause of idiopathic slow-transit constipation.
Knowles
C H
CH
Academic Department of Surgery, Royal London School of Medicine and Dentistry, Whitechapel, United Kingdom.
Gayther
S A
SA
Scott
M
M
Ramus
S
S
Anand
P
P
Williams
N S
NS
Ponder
B A
BA
D000328:Adult; D003248:Constipation / Q000235:genetics*; D005260:Female; D005772:Gastrointestinal Transit; D018095:Germ-Line Mutation; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006801:Humans; D008297:Male; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009692:Nucleic Acid Heteroduplexes; D018807:Polymorphism, Single-Stranded Conformational; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*
C495039:GDNF protein, human; D051100:Glial Cell Line-Derived Neurotrophic Factor; C000715470:MAS1 protein, human; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D009692:Nucleic Acid Heteroduplexes; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins