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)

Multiple exostosis, biparietal foramina, minor craniofacial abnormalities, and mental retardation are characteristic of the syndrome associated with a proximal deletion of 11p (MIM # 601224), which has been shown to be a true contiguous gene deletion syndrome. The presence of multiple exostosis is associated with deletion of the EXT2 gene. Similarly, the presence of biparietal foramina has been shown to be associated with the deletion of ALX4 located proximally to EXT2. Specific genes related to mental retardation and craniofacial abnormalities, however, have yet to be identified. We report on a family with a microdeletion of 11(pll.2p11.2) with multiple exostosis and biparietal foramina without mental retardation or craniofacial abnormalities. Our results suggest that genes related to mental retardation and craniofacial development must be located outside of the D11S1785-D11S1385 region.
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PMID:Familial case of Potocki-Shaffer syndrome associated with microdeletion of EXT2 and ALX4. 1190 36

Aniridia, Wilms tumor, genitourinary abnormalities, growth and mental retardation are the cardinal features of the WAGR 11p13 deletion syndrome. The Potocki-Schaffer syndrome or proximal 11p deletion syndrome (previously DEFECT11 syndrome) is a contiguous gene syndrome associated with deletions in 11p11.2, principal features of which are multiple exostoses and enlarged parietal foramina. Mental handicap, facial dysmorphism and craniosynostosis may also be associated. We report a patient with combined WAGR and Potocki-Shaffer syndromes, and obesity. She presented with aniridia, cataract, nystagmus, corneal ulcers and bilateral congenital ptosis. A left nephroblastoma was detected at 15 months. Other features included moderate developmental delay, growth deficiency, facial dysmorphism, multiple exostoses and cranial lacunae. High-resolution and molecular cytogenetics confirmed a del(11)(p11.2p14.1) deletion with a proximal breakpoint between the cosmid DO8153 and the BAC RP11-104M24 to a distal breakpoint between cosmids CO8160 (D11S151) and F1238 (D11S1446). The deletion therefore includes EXT2, ALX4, WT1 and PAX6. This case appears to be the second patient reported with this combined deletion syndrome and confirms the association of obesity in the WAGR spectrum, a feature previously reported in four cases, and for which the acronym WAGRO has been suggested. Molecular and follow-up data on the original WAGRO case are briefly presented.
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PMID:Combination of WAGR and Potocki-Shaffer contiguous deletion syndromes in a patient with an 11p11.2-p14 deletion. 1570 31

Potocki-Shaffer syndrome (PSS) is a contiguous gene deletion syndrome that results from haploinsufficiency of at least two genes within the short arm of chromosome 11[del(11)(p11.2p12)]. The clinical features of PSS can include developmental delay, mental retardation, multiple exostoses, parietal foramina, enlarged anterior fontanel, minor craniofacial anomalies, ophthalmologic anomalies, and genital abnormalities in males. We constructed a natural panel of 11p11.2-p13 deletions using cell lines from 10 affected individuals, fluorescence in situ hybridization (FISH), microsatellite analyses, and array-based comparative genomic hybridization (array CGH). We then compared the deletion sizes and clinical features between affected individuals. The full spectrum of PSS manifests when deletions are at least 2.1 Mb in size, spanning from D11S1393 to D11S1385/D11S1319 (44.6-46.7 Mb from the 11p terminus) and encompassing EXT2, responsible for multiple exostoses, and ALX4, causing parietal foramina. Yet one subject with parietal foramina whose deletion does not include ALX4 indicates that ALX4 in this subject may be rendered functionally haploinsufficient by a position effect. Based on comparative deletion mapping of eight individuals with the full PSS syndrome including mental retardation and two PSS families with no mental retardation, at least one gene related to mental retardation is likely located between D11S554 and D11S1385/D11S1319, 45.6-46.7 Mb from the 11p terminus.
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PMID:Construction of a natural panel of 11p11.2 deletions and further delineation of the critical region involved in Potocki-Shaffer syndrome. 1585 40

Heterozygous mutations of the homeobox genes ALX4 and MSX2 cause skull defects termed enlarged parietal foramina (PFM) and cranium bifidum (CB); a single MSX2 mutation has been documented in a unique craniosynostosis (CRS) family. However, the relative mutational contribution of these genes to PFM/CB and CRS is not known and information on genotype-phenotype correlations is incomplete. We analysed ALX4 and MSX2 in 11 new unrelated cases or families with PFM/CB, 181 cases of CRS, and a single family segregating a submicroscopic deletion of 11p11.2, including ALX4. We explored the correlations between skull defect size and age, gene, and mutation type, and reviewed additional phenotypic manifestations. Four PFM cases had mutations in either ALX4 or MSX2; including previous families, we have identified six ALX4 and six MSX2 mutations, accounting for 11/13 familial, but only 1/6 sporadic cases. The deletion family confirms the delineation of a mental retardation locus to within 1.1 Mb region of 11p11.2. Overall, no significant size difference was found between ALX4- and MSX2-related skull defects, but the ALX4 mutation p.R218Q tends to result in persistent CB and is associated with anatomical abnormalities of the posterior fossa. We conclude that PFM caused by mutations in ALX4 and MSX2 have a similar prevalence and are usually clinically indistinguishable. Mutation screening has a high pickup rate in PFM, especially in familial cases, but is not indicated in CRS.
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PMID:Enlarged parietal foramina caused by mutations in the homeobox genes ALX4 and MSX2: from genotype to phenotype. 1631 23

The proximal chromosome 11p contiguous gene deletion syndrome (P11pDS), also known as Potocki-Shaffer syndrome (PSS) or DEFECT 11 (OMIM 601224), is a disorder associated with foramina parietalia permagna and multiple osteochondroma (exostoses). Additional features include mental retardation, craniofacial anomalies, seizures and genitourinary abnormalities. Here, clinico-pathological findings of a unique patient with all of these features and, additionally, enlarged ventricles, hypertrophic obstructive cardiomyopathy and adipositas are described. The brain showed malformative lesions with hallmarks of disturbed bulk growth including micrencephaly, periventricular nodular heterotopias and focal cortical dysplasia in the nodulus of the cerebellar vermis. In addition, symmetric foci with vacuolation of the underlying neuropil, intermingled macrophages and large bizarre, partially vacuolated, reactive astrocytes were found. The proximal short arm of chromosome 11 harbors several candidate genes that could explain the patient's signs and symptoms including ALX4 and EXT2, which are always present in the interstitial deletion of the short arm of chromosome 11 in PSS. In addition, MYBPC3 would be a good candidate for the hypertrophic cardiomyopathy. Furthermore, adipositas might be related to the MAPK8IP1 gene. To the best of our knowledge, the present patient is the oldest one so far described with PSS phenotype and the only case that has undergone detailed neuropathological investigation.
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PMID:Proximal chromosome 11p contiguous gene deletion syndrome phenotype: case report and review of the literature. 1729 Sep 30