Mapping of a gene for severe pediatric gastroesophageal reflux to chromosome 13q14

Context Gastroesophageal reflux (CER) has not previously been widely regard ed as a hereditary disease, A few reports have suggested, however, that a g enetic component may contribute to the incidence of GER, especially in its severe or chronic forms. Objective To identify a genetic locus that cosegregates with a severe pedia tric GER phenotype in families with multiple affected members. Design A genome-wide scan of families affected by severe pediatric GER usin g polymorphic microsatellite markers spaced at an average of 8 centimorgans (cM), followed by haplotyping and by pairwise and multipoint linkage analy ses. Setting General US community, with research performed in a university terti ary care hospital. Subjects Affected and unaffected family members from 5 f amilies having multiple individuals affected by severe pediatric GER, ident ified through a patient support group. Main Outcome Measures Determination of inheritance patterns and linkage of a genetic locus with the severe pediatric GER phenotype by logarithm-of-odd s (lod) score analysis, considering a lod score of 3 or greater as evidence of linkage. Results In these families, severe pediatric GER followed an autosomal domin ant hereditary pattern with high penetrance. A gene for severe pediatric GE R was mapped to a 13-cM region on chromosome 13q between microsatellite mar kers D13S171 and D13S263. A maximum multifamily 2-point lod score of 5.58 a nd a maximum multifamily multipoint lod score of 7.15 were obtained for mar ker D13S1253 at map position 35 cM when presumptively affected persons were modeled as unknown (a maximum multipoint score of 4.88 was obtained when p resumptively affected persons were modeled as unaffected). Conclusion These data suggest that a gene for severe pediatric GER maps to chromosome 13q14.