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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The abnormal phenotype and/or mental retardation seen in persons with small marker X (mar(X)) chromosomes has been hypothesized to be due to the loss of the X inactivation center (XIC) at Xq13.2, resulting in two active copies of genes in the pericentromeric region. In order to define precisely the DNA content of mar(X) chromosomes and to correlate phenotype with karyotype, we studied small mar(X) chromosomes, using FISH with probes in the juxtacentromeric region. One of the probes was a 40-kb genomic cosmid for the XIST gene, which maps to the smallest interval known to contain the XIC and is thought to be involved in X inactivation. Our findings reveal that small mar(X) chromosomes do not include the XIC and therefore cannot be subject to X inactivation, supporting the premise that abnormal dosage of expressed genes in the pericentromeric region of the X generates the aberrant phenotype seen in patients with small mar(X) chromosomes.
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PMID:Small marker X chromosomes lack the X inactivation center: implications for karyotype/phenotype correlations. 802 55

In a description of 8 girls who had Ullrich-Turner syndrome (UTS) with a small r(X), mental retardation, and other unusual findings, it was hypothesized that the distinctive phenotype was associated with the loss of the X inactivation center from the r(X) and lack of genetic inactivation of the ring [Van Dyke et al., 1992]. Here, we present a 17-year-old young woman with 45,X/46,X,r(X)(?p11q13) mosaicism, Ullrich-Turner syndrome, and normal intelligence. In situ hybridization with the X-centromere DNA probe DXZ1 (Oncor, Inc., Gaithersburg, MD) was performed on previously G-banded slides, and the probe hybridized to the centromere regions of the normal X and the ring. The r(X) appears to be inactivated since a buccal smear demonstrated 5% Barr bodies. Furthermore, DAPI stain and FISH analysis with the X-centromere DNA probe DXZ1 was employed to distinguish the inactive X from the active X, and verified the presence of a sex chromatin mass in fibroblasts. These observations are consistent with the active-ring-X-and-mental-retardation hypothesis since the ring in this patient, although very small, appears to be normally inactivated and she has normal intelligence.
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PMID:X-inactivation pattern in an Ullrich-Turner syndrome patient with a small ring X and normal intelligence. 825 12

We report the application of chromosome painting using FISH (fluorescence) in situ hybridization) to demonstrate the origin of a de novo 6q+ marker chromosome. A girl with a mental retardation/multiple malformation syndrome was shown to have the karyotype 46,XX, 6q+. Banding analysis could not determine the origin of the extra chromosomal material. Using FISH with a chromosome-6-specific library we showed that the marker chromosome was completely painted, indicating an origin from chromosome 6. The child's phenotype was compared with previously reported cases with partial chromosome 6 trisomy. A clinically recognized syndrome emerged, although she apparently also demonstrated novel features.
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PMID:Chromosome painting using FISH (fluorescence in situ hybridization) with chromosome-6-specific library demonstrates the origin of a de novo 6q+ marker chromosome. 837 3

DiGeorge syndrome (DGS) is predominantly caused by partial monosomy 22q11, but a subset of patients with DGS show deletions of 10p or other chromosomal abnormalities. The authors describe a 20 months old girl with DGS and a monosomy 10p bringing the number of DGS patients with this chromosomal abnormality to nine. She has a monosomy 10p13-pter and a trisomy 10q26-qter due to a meiotic recombination of a maternal inversion (10) (p13q26). The proposita's phenotype demonstrates typical features of the del (10p) syndrome which include mental retardation, abnormally shaped skull, hypertelorism, low nasal bridge, micrognathia, dysmorphic low set ears, short neck, foot abnormalities, and cardiac defect. The diagnosis of DGS was made unequivocally within the first weeks of life because of the typical features-cardiac defect, hypoplastic thymus, T-cell defect, hypocalcemia, and hypoparathyroidism. The common DGS mutation-microdeletion 22q11-was excluded by FISH analysis, and the breakpoints on chromosome 10 were mapped between D10S189 and D10S191 on the short arm and proximal to D10S25 on the long arm.
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PMID:DiGeorge syndrome and partial monosomy 10p: case report and review. 854 Jun 88

We studied 16 cases of 8p duplications, with a karyotype 46,XX or XY,dup(8p), associated with mental retardation, facial dysmorphisms, and brain defects. We demonstrate that these 8p rearrangements can be either dicentric (6 cases) with the second centromere at the tip of the short arm or monocentric (10 cases). The distal 8p23 region, from D8S349 to the telomere, including the defensin 1 locus, is deleted in all the cases. The region spanning from D8S252 to D8S265, at the proximal 8p23 region, is present in single copy, and the remaining part of the abnormal 8 short arm is duplicated in the dicentric cases and partially duplicated in the monocentric ones. The distal edge of the duplication always spans up to D8S552 (8p23.1), while its proximal edge includes the centromere in the dicentric cases and varies from case to case in the monocentric ones. The analysis of DNA polymorphisms indicates that the rearrangement is consistently of maternal origin. In the deleted region, only paternal alleles were present in the patient. In the duplicated region, besides one paternal allele, some loci showed two different maternal alleles, while others, which were duplicated by FISH analysis, showed only one maternal allele. We hypothesize that, at maternal meiosis I, there was abnormal pairing of chromosomes 8 followed by anomalous crossover at the regions delimited by D8S552 and D8S35 and by D8S252 and D8S349, which presumably contain inverted repeated sequences. The resulting dicentric chromosome, 8qter-8p23.1(D8S552)::8p23.1-(D8S35)-8q ter, due to the presence of two centromeres, breaks at anaphase I, generating an inverted duplicated 8p, dicentric if the breakage occurs at the centromere or monocentric if it occurs between centromeres.
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PMID:The same molecular mechanism at the maternal meiosis I produces mono- and dicentric 8p duplications. 864 43

Smith-Magenis syndrome (SMS) is a clinically recognizable, multiple congenital anomalies/mental retardation syndrome caused by an interstitial deletion involving band p11.2 of chromosome 17. Toward the molecular definition of the interval defining this microdeletion syndrome, 62 unrelated SMS patients in conjunction with 70 available unaffected parents were molecularly analyzed with respect to the presence or absence of 14 loci in the proximal region of the short arm of chromosome 17. A multifaceted approach was used to determine deletion status at the various loci that combined (i) FISH analysis, (ii)PCR and Southern analysis of somatic cell hybrids retaining the deleted chromosome 17 from selected patients, and (iii) genotype determination of patients for whom a parent(s) was available at four microsatellite marker loci and at four loci with associated RFLPs. The relative order of two novel anonymous markers and a new microsatellite marker was determined in 17p11.2. The results confirmed that the proximal deletion breakpoint in the majority of SMS patients is located between markers D17S58 (EW301) and D17S446 (FG1) within the 17p11.1-17p11.2 region. The common distal breakpoint was mapped between markers cCI17-638, which lies distal to D17S71, and cCI17-498, which lies proximal to the Charcot Marie-Tooth disease type 1A locus. The locus D17S258 was found to be deleted in all 62 patients, and probes from this region can be used for diagnosis of the SMS deletion by FISH. Ten patients demonstrated molecularly distinct deletions; of these, two patients had smaller deletions and will enable the definition of the critical interval for SMS.
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PMID:Molecular analyses of 17p11.2 deletions in 62 Smith-Magenis syndrome patients. 865 Dec 84

M6 is a neuronal membrane glycoprotein that may have an important role in neural development. This molecule was initially defined by a monoclonal antibody that affected the survival of cultured cerebellar neurons and the outgrowth of neurites. The nature of the antigen was discovered by expression cDNA cloning using this monoclonal antibody. Two distinct murine M6 cDNAs (designated M6a and M6b) whose deduced amino acid sequences were remarkably similar to that of the myelin proteolipid protein were previously isolated. We have isolated partial human cDNA and genomic clones encoding M6a and M6b and have characterized them by restriction mapping, Southern hybridization with cDNA probes, and sequence analysis. We have localized these genes within the human genome by FISH (fluorescence in situ hybridization). The human M6a gene is located at 4q34, and the M6b gene is located at Xp22.2. A number of human neurological disorders have been mapped to the Xp22 region, including Aicardi syndrome (MIM 304050), Rett syndrome (MIM 312750), X-linked Charcot-Marie-Tooth neuropathy (MIM 302801), and X-linked mental retardation syndromes (MRX1, MIM 309530). This raises the possibility that a defect in the M6b gene is responsible for one of these neurological disorders.
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PMID:Chromosomal mapping of the human M6 genes. 866 Oct 15

Human chromosomes terminate with specialized telomeric structures including the simple tandem repeat (TTAGGG)n and additional complex subtelomeric repeats. Unique sequence DNA for each telomere is located 100-300 kilobases (kb) from the end of most chromosomes. A high concentration of genes and a number of candidate genes for recognizable syndromes are known to be present in telomeric regions. The human telomeric regions represent a major diagnostic challenge in clinical cytogenetics, because most of the terminal bands are G negative, and cryptic deletions and translocations in the telomeric regions are therefore difficult to detect by conventional cytogenetic methods. In fact, several submicroscopic chromosomal abnormalities in patients with undiagnosed mental retardation or multiple congenital anomalies have been identified by other molecular methods such as DNA polymorphism analysis. To improve the sensitivity for deletion detection and to determine whether such cryptic rearrangements represent a significant source of human pathology that has not been previously appreciated, it would be valuable to have specific FISH probes for all human telomeres. We report here the isolation and characterization of a complete set of specific FISH probes representing each human telomere. As most of these clones are at a known distance of within 100-300 kb from the end of the chromosome arm, this provides a 10-fold improvement in deletion detection sensitivity compared with high-resolution cytogenetics (2-3 Mb resolution). While testing these probes, we serendipitously identified a family with multiple members carrying a cryptic 1q;11p rearrangement in the balanced or unbalanced state.
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PMID:A complete set of human telomeric probes and their clinical application. National Institutes of Health and Institute of Molecular Medicine collaboration. 878 25

We report on a folate sensitive fragile site at Xq27-28 in a girl with a multiple congenital anomalies and mental retardation syndrome, who also carries a duplication of the long arm of chromosome 8. The fragile site was shown by FISH to be distal to both FRAXA and FRAXE. DNA hybridisation with probe OxF14 showed the amplification of the CGG repeats of locus FRAXF in the patient and in her clinically normal mother.
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PMID:FRAXF in a patient with chromosome 8 duplication. 881 52

We report on a 15-year-old girl with mental retardation, obesity, short stature and minor anomalies. She had 47 chromosomes with a minute extra ring which was identified by FISH to be derived from chromosome 17.
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PMID:Identification of a supernumerary marker derived from chromosome 17 using FISH. 884 6


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