Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917816 (mental retardation)
 15,867 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several mutations involving the fibroblast growth factor receptor (FGFR) gene family have been identified in association with phenotypically distinct forms of craniosynostosis. One such point mutation, resulting in the substitution of proline by arginine in a critical region of the linker region between the first and second immunoglobulin-like domains, is associated with highly specific phenotypic consequences in that mutation at this point in FGFR1 results in Pfeiffer syndrome and analogous mutation in FGFR2 results in Apert syndrome. We now show that a much more variable clinical presentation accompanies analogous mutation in the FGFR3 gene. Specifically, mental retardation, apparently unrelated to the management of the craniosynostosis, appears to be a variable clinical consequence of this FGFR3 mutation.
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PMID:Craniosynostosis associated with FGFR3 pro250arg mutation results in a range of clinical presentations including unisutural sporadic craniosynostosis. 927 53

Wolf-Hirschhorn syndrome (WHS) is a deletion syndrome caused by segmental haploidy of chromosome 4p16.3. Its hallmark features include a 'Greek warrior helmet' facial appearance, mental retardation, various midline defects and seizures. The WHS critical region (WHSCR) lies between the Huntington's disease gene, HD, and FGFR3. In mice, the homologs of these genes map to chromosome 5 in a region of conserved synteny with human 4p16.3. To derive mouse models of WHS and map genes responsible for subphenotypes of the syndrome, five mouse lines bearing radiation-induced deletions spanning the WHSCR syntenic region were generated and characterized. Similar to WHS patients, these animals were growth-retarded, were susceptible to seizures and showed midline (palate closure, tail kinks), craniofacial and ocular anomalies (colobomas, corneal opacities). Other phenotypes included cerebellar hypoplasia and a shortened cerebral cortex. Expression of WHS-like traits was variable and influenced by strain background and deletion size. These mice represent the first animal models for WHS. This collection of nested chromosomal deletions will be useful for mapping and identifying loci responsible for the various subphenotypes of WHS, and provides a paradigm for the dissection of other deletion syndromes using the mouse.
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PMID:Mouse models for the Wolf-Hirschhorn deletion syndrome. 1115 56

Wolf-Hirschhorn syndrome (WHS) is a rare chromosomal disorder attributable to a deletion at the short arm of chromosome 4. This syndrome is associated with characteristic facial appearance, multiple congenital abnormalities, mental retardation, feeding difficulties and failure to thrive. We report two girls with WHS who developed myelodysplastic syndrome (MDS). According to the "Category, Cytology, Cytogenetic (CCC)"classification of childhood MDS, patient 1 had refractory cytopenia with ring sideroblasts at the age of 6 years, while patient 2 had refractory cytopenia with dysplasia at the age of 5-1/2 years. Patient 1 progressed to refractory cytopenia with excess blasts within a year, while patient 2 progressed to acute lymphoblastic leukemia within 1 month of presentation. It is possible that allelic loss of a tumor suppressor gene such as WHSC1 and/or FGFR3 from the deleted segment 4p16.3 plays a critical role in the process of malignant transformation. To our knowledge, this is the first report of severe hematological complications like MDS and leukemia in children with WHS and may be an important genetic model for understanding malignant hematological transformation. This report also underscores the importance of evaluating children with WHS for hematopoietic dysfunction.
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PMID:Malignant hematological disorders in children with Wolf-Hirschhorn syndrome. 1274 63