Genome-wide high-density SNP-based linkage analysis of infantile hypertrophic pyloric stenosis identifies loci on chromosomes 11q14-q22 and Xq23.
Infantile hypertrophic pyloric stenosis (IHPS) has an incidence of 1-8 per 1000 live births and is inherited as a complex sex-modified multifactorial trait with a striking male preponderance. Syndromic and monogenic forms exist, and two loci have been identified. Infants present with vomiting due to gastric-outlet obstruction caused by hypertrophy of the smooth muscle of the pylorus. A genome-wide SNP-based high-density linkage scan was carried out on 81 IHPS pedigrees. Nonparametric and parametric linkage analysis identified loci on chromosomes 11q14-q22 (Z(max) = 3.9, p < 0.0001; HLOD(max) = 3.4, alpha = 0.34) and Xq23 (Z(max) = 4.3, p < 0.00001; HLOD(max) = 4.8, alpha = 0.56). The two linked chromosomal regions each harbor functional candidate genes that are members of the canonical transient receptor potential (TRPC) family of ion channels and have a potential role in smooth-muscle control and hypertrophy.
Everett
Kate V
KV
University College London Institute of Child Health, London WC1N 1EH, UK. kate.everett@ucl.ac.uk
Chioza
Barry A
BA
Georgoula
Christina
C
Reece
Ashley
A
Capon
Francesca
F
Parker
Keith A
KA
Cord-Udy
Cathy
C
McKeigue
Paul
P
Mitton
Sally
S
Pierro
Agostino
A
Puri
Prem
P
Mitchison
Hannah M
HM
Chung
Eddie M K
EM
Gardiner
R Mark
RM
D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D046248:Pyloric Stenosis, Hypertrophic / Q000235:genetics*; D012744:Sex Ratio