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)

Supernumerary marker chromosomes (SMCs) have a reported frequency in the prenatal and newborn population ranging from 0.04% to 0.08% and about 37% of diagnosed SMCs are associated with an abnormal phenotype. Around 7.5% of them are derived from chromosome 22. SMCs(22) that result in tri- or tetrasomy of band 22q11.2 are associated with Cat-eye syndrome (CES), a syndrome of variable penetrance and affectation. CES-like phenotype has been also related to 22q11.2 interstitial duplications and der(22) syndrome. The 22q11.2 region, also involved in the velocardiofacial microdeletional syndrome, presents high susceptibility to chromosomal rearrangements due to the presence of low-copy repeats sequences (LCR22). Another region in the genome rich in LCR is 17p and five recurrent disorders have been mapped on the region 17p11-p13. Some chromosomal imbalances affecting the 17p13.3 subtelomeric region have been reported, related to cryptic unbalanced translocations and associated, in most cases, to mental retardation and dysmorphic features. We report on a healthy male carrier of a SMC that was identified as a +der(22)t(17;22)(p13.3;q11.2) consequence of an abnormal 3:1 segregation of the paternal t(17;22) and we have determined the approximate size of the trisomic regions, comparing the obtained results with other reported imbalances involving 22q11.2 and 17pter.
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PMID:Trisomy of 19.4 Mb region of chromosome 22 and subtelomeric 17p identified in a male without clinical affectation. 1785 59

We report on the identification of a 0.3 Mb inherited recurrent but variable copy-number gain at Xq28 in affected males of four unrelated families with X-linked mental retardation (MR). All aberrations segregate with the disease in the families, and the carrier mothers show nonrandom X chromosome inactivation. Tiling Xq28-region-specific oligo array revealed that all aberrations start at the beginning of the low copy repeat LCR-K1, at position 153.20 Mb, and end just distal to LCR-L2, at 153.54 Mb. The copy-number gain always includes 18 annotated genes, of which RPL10, ATP6AP1 and GDI1 are highly expressed in brain. From these, GDI1 is the most likely candidate gene. Its copy number correlates with the severity of clinical features, because it is duplicated in one family with nonsyndromic moderate MR, is triplicated in males from two families with mild MR and additional features, and is present in five copies in a fourth family with a severe syndromic form of MR. Moreover, expression analysis revealed copy-number-dependent increased mRNA levels in affected patients compared to control individuals. Interestingly, analysis of the breakpoint regions suggests a recombination mechanism that involves two adjacent but different sets of low copy repeats. Taken together, our data strongly suggest that an increased expression of GDI1 results in impaired cognition in a dosage-dependent manner. Moreover, these data also imply that a copy-number gain of an individual gene present in the larger genomic aberration that leads to the severe MECP2 duplication syndrome can of itself result in a clinical phenotype as well.
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PMID:Dosage-dependent severity of the phenotype in patients with mental retardation due to a recurrent copy-number gain at Xq28 mediated by an unusual recombination. 2038 Sep 30

We have investigated four approximately 1.6-Mb microduplications and 55 smaller 350-680-kb microduplications at 15q13.2-q13.3 involving the CHRNA7 gene that were detected by clinical microarray analysis. Applying high-resolution array-CGH, we mapped all 118 chromosomal breakpoints of these microduplications. We also sequenced 26 small microduplication breakpoints that were clustering at hotspots of nonallelic homologous recombination (NAHR). All four large microduplications likely arose by NAHR between BP4 and BP5 LCRs, and 54 small microduplications arose by NAHR between two CHRNA7-LCR copies. We identified two classes of approximately 1.6-Mb microduplications and five classes of small microduplications differing in duplication size, and show that they duplicate the entire CHRNA7. We propose that size differences among small microduplications result from preexisting heterogeneity of the common BP4-BP5 inversion. Clinical data and family histories of 11 patients with small microduplications involving CHRNA7 suggest that these microduplications might be associated with developmental delay/mental retardation, muscular hypotonia, and a variety of neuropsychiatric disorders. However, we conclude that these microduplications and their associated potential for increased dosage of the CHRNA7-encoded alpha 7 subunit of nicotinic acetylcholine receptors are of uncertain clinical significance at present. Nevertheless, if they prove to have a pathological effects, their high frequency could make them a common risk factor for many neurobehavioral disorders.
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PMID:Structures and molecular mechanisms for common 15q13.3 microduplications involving CHRNA7: benign or pathological? 2050 39