J. Amiel et al., Large-scale deletions and SMADIP1 truncating mutations in syndromic hirschsprung disease with involvement of midline structures, AM J HU GEN, 69(6), 2001, pp. 1370-1377
Citations number
12
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Molecular Biology & Genetics
Hirschsprung disease (HSCR) is a common malformation of neural-crest-derive
d enteric neurons that is frequently associated with other congenital abnor
malities. The SMADIP1 gene recently has been recognized as disease causing
in some patients with 2q22 chromosomal rearrangement, resulting in syndromi
c HSCR with mental retardation, with microcephaly, and with facial dysmorph
ism. We screened 19 patients with HSCR and mental retardation and eventuall
y identified large-scale SMADIP1 deletions or truncating mutations in 8 of
19 patients. These results allow further delineation of the spectrum of mal
formations ascribed to SMADIP1 haploinsufficiency, which includes frequent
features such as hypospadias and agenesis of the corpus callosum. Thus, SMA
DIP1, which encodes a transcriptional corepressor of Smad target genes, may
play a role not only in the patterning of neural-crest-derived cells and o
f CNS but also in the development of midline structures in humans.