title: Linkage of monogenic infantile hypertrophic pyloric stenosis to chromosome 16p12-p13 and evidence for genetic heterogeneity.
abstract: Infantile hypertrophic pyloric stenosis (IHPS) is the most common form of bowel obstruction in infancy. The disease affects males four times more often than females and is considered a paradigm for the sex-modified model of multifactorial inheritance. However, pedigrees consistent with autosomal dominant inheritance have also been documented. We analyzed a 3-generation family with IHPS including 10 affected individuals (5 males and 5 females) and mapped the underlying disease locus to chromosome 16p12-p13 (LOD score 3.23) by using a single-nucleotide polymorphism-based genomewide scan. The analysis of 10 additional multiplex pedigrees yielded negative or nonsignificant LOD scores, indicating the presence of locus heterogeneity. Sequence analysis of candidate genes from the chromosome 16 disease interval excluded the presence of pathogenic mutations in the GRIN2A and MYH11 genes.
authors.affiliation: Department of Paediatrics and Child Health, The Rayne Building, University College London, WC1E 6JJ London, UK.
authors.forename: Francesca
authors.initials: F
authors.lastname: Capon
authors.forename: Ashley
authors.initials: A
authors.lastname: Reece
authors.forename: Rathi
authors.initials: R
authors.lastname: Ravindrarajah
authors.forename: Eddie
authors.initials: E
authors.lastname: Chung
mesh_terms: D002874:Chromosome Mapping; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D005260:Female; D018740:Genetic Heterogeneity; D008040:Genetic Linkage; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D010375:Pedigree; D046248:Pyloric Stenosis, Hypertrophic / Q000235:genetics*