Large-scale deletions and SMADIP1 truncating mutations in syndromic hirschsprung disease with involvement of midline structures

Citation
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
Journal title
AMERICAN JOURNAL OF HUMAN GENETICS
ISSN journal
00029297 → ACNP
Volume
69
Issue
6
Year of publication
2001
Pages
1370 - 1377
Database
ISI
SICI code
0002-9297(200112)69:6<1370:LDASTM>2.0.ZU;2-A
Abstract
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.