Common variants near MBNL1 and NKX2-5 are associated with infantile hypertrophic pyloric stenosis

Stomach development, stem cells and disease

“…Pyloric stenosis is in fact a complex disorder influenced by genetic and environmental factors, including maternal smoking and alcohol use. The implication of common variants near MBNL1 and NKX2-5 in a genome-wide association study (Feenstra et al, 2012) is noteworthy because Nkx2-5 is expressed specifically in the developing pyloric sphincter and is necessary for its proper formation in chick and mouse embryos (Smith et al, 2000;Theodosiou and Tabin, 2005;Udager et al, 2014). Nitric oxide deficiency (Vanderwinden et al, 1992;Huang et al, 1993) and defects in the ENS (Guarino et al, 2000) or interstitial cells of Cajal (Vanderwinden and Rumessen, 1999) are also associated with pyloric stenosis and are likely to affect synchronized muscle contraction.…”

A novel missense mutation in the transcription factor FOXF1 cosegregating with infantile hypertrophic pyloric stenosis in the extended pedigree linked to IHPS5 on chromosome 16q24

“…However, it should be pointed out that this family did not show linkage to any of the other reported familial IHPS loci so any interaction is likely to be with variants at other loci. For example, a genome wide association (GWA) study has identified three variants significantly associated with IHPS which have implicated the genes MBNL1 and NKX2-5 31 . Two of these variants were shown to be associated in an independent Northern European replication cohort 32 .…”

Genomics, Personalized Medicine, and Pediatrics

“…29 However, GWAS have already proved extremely helpful in better understanding the underlying biology of literally scores of conditions, including many that affect children. 27,30,31 …”