HOX11L1: a promoter study to evaluate possible expression defects in intestinal motility disorders

Intestinal Neuronal Dysplasia (IND) is a congenital disorder characterized by intestinal motility defects associated with hyperplasia of enteric ganglia. A phenotype resembling human IND has been observed in mice knocked-out for a member of the Hox11 homeobox gene family, Hox11l1, suggesting that the human homologue of this gene could be responsible for congenital disorders of intestinal innervation. However, previous mutation analysis of the coding sequence of the HOX11L1 gene in patients affected with IND detected neither mutations nor other nucleotide variants. In the present work, a detailed study of the non coding promoter region of this gene was undertaken in patients affected with IND, with Hirschsprung associated IND and with neurogenic chronic intestinal pseudo-obstruction. No alterations potentially impairing expression of HOX11L1, such as nucleotide variants, small deletions or cytogenetic alterations, could be identified thus further excluding the direct involvement of this gene in the pathogenesis of human intestinal motility disorders.