Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mutations in ZFHX1B, encoding Smad-interacting protein 1 (SIP1), have been recently reported to cause a form of Hirschsprung disease (HSCR). Patients with ZFHX1B deficiency typically show mental retardation, delayed motor development, epilepsy, microcephaly, distinct facial features, and/or congenital heart disease, in addition to the cardinal form of HSCR. To investigate the breadth of clinical variation, we studied DNA samples from six patients with clinical profiles quite similar to those described elsewhere for ZFHX1B deficiency, except that they did not have HSCR. The results showed the previously reported R695X mutation to be present in three cases, with three novel mutations-a 2-bp insertion (760insCA resulting in 254fs262X), a single-base deletion (270delG resulting in 91fs107X), and a 2-bp deletion (2178delTT resulting in 727fs754X)-newly identified in the other three. All mutations occurred in one allele and were de novo events. These results demonstrate that ZFHX1B deficiency is an autosomal dominant complex developmental disorder and that individuals with functional null mutations present with mental retardation, delayed motor development, epilepsy, and a wide spectrum of clinically heterogeneous features suggestive of neurocristopathies at the cephalic, cardiac, and vagal levels.
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PMID:Nonsense and frameshift mutations in ZFHX1B, encoding Smad-interacting protein 1, cause a complex developmental disorder with a great variety of clinical features. 1159 33

Hirschsprung disease (HSCR) is a common malformation of neural-crest-derived enteric neurons that is frequently associated with other congenital abnormalities. The SMADIP1 gene recently has been recognized as disease causing in some patients with 2q22 chromosomal rearrangement, resulting in syndromic HSCR with mental retardation, with microcephaly, and with facial dysmorphism. We screened 19 patients with HSCR and mental retardation and eventually identified large-scale SMADIP1 deletions or truncating mutations in 8 of 19 patients. These results allow further delineation of the spectrum of malformations ascribed to SMADIP1 haploinsufficiency, which includes frequent features such as hypospadias and agenesis of the corpus callosum. Thus, SMADIP1, which encodes a transcriptional corepressor of Smad target genes, may play a role not only in the patterning of neural-crest-derived cells and of CNS but also in the development of midline structures in humans.
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PMID:Large-scale deletions and SMADIP1 truncating mutations in syndromic Hirschsprung disease with involvement of midline structures. 1159 72

Mowat-Wilson syndrome (MWS) is a recently delineated mental retardation (MR)-multiple congenital anomaly syndrome, characterized by typical facies, severe MR, epilepsy, and variable congenital malformations, including Hirschsprung disease (HSCR), genital anomalies, congenital heart disease (CHD), and agenesis of the corpus callosum (ACC). It is caused by de novo heterozygous mutations or deletions of the ZFHX1B gene located at 2q22. ZFHX1B encodes Smad-interacting protein-1 (SMADIP1 or SIP1), a transcriptional corepressor involved in the transforming growth factor-beta signaling pathway. It is a highly evolutionarily conserved gene, widely expressed in embryological development. Over 100 mutations have been described in patients with clinically typical MWS, who almost always have whole gene deletions or truncating mutations (nonsense or frameshift) of ZFHX1B, suggesting that haploinsufficiency is the basis of MWS pathology. No obvious genotype-phenotype correlation could be identified so far, but atypical phenotypes have been reported with missense or splice mutations in the ZFHX1B gene. In this work we describe 40 novel mutations and we summarize the various mutational reports published since the identification of the causative gene.
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PMID:ZFHX1B mutations in patients with Mowat-Wilson syndrome. 1720 59