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)

The fragile-X syndrome of mental retardation is associated with an expansion in the number of CGG repeats present in the FMR1 gene. The repeat region is within sequences characteristic of a CpG island. Methylation of CpG dinucleotides that are 5' to the CGG repeat has been shown to occur on the inactive X chromosome of normal females and on the X chromosome of affected fragile-X males, and is correlated with silencing of the FMR1 gene. The methylation status of CpG sites 3' to the repeat and within the repeat itself has not previously been reported. We have used two methylation-sensitive restriction enzymes, AciI and Fnu4HI, to further characterize the methylation pattern of the FMR1 CpG island in normal individuals and in those carrying fragile-X mutations. Our results indicate that: (i) CpG dinucleotides on the 3' side of the CGG repeat are part of the CpG island that is methylated during inactivation of a normal X chromosome in females; (ii) the CGG repeats are also part of the CpG island and are extensively methylated as a result of normal X-chromosome inactivation; (iii) similar to normal males, unaffected fragile-X males with small CGG expansions are unmethylated in the CpG island; for affected males, the patterns of methylation are similar to those of a normal, inactive X chromosome; (iv) in contrast to the partial methylation observed for certain sites in lymphocyte DNA, complete methylation was observed in DNA from cell lines containing either a normal inactive X chromosome or a fragile-X chromosome from an affected male.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Methylation analysis of CGG sites in the CpG island of the human FMR1 gene. 130 Nov 65

Mental retardation unassociated with the Fragile X syndrome accounts for up to 60% of patients with X-linked mental retardation. In this investigation, we report on a family with mild non-specific X-linked mental retardation (MRX) without other apparent phenotypic abnormalities. Linkage analysis on 27 relatives using 18 polymorphic markers spanning the X-chromosome demonstrated close linkage to DXYS1 with a peak LOD score of 2.14 at a theta of 0. Numerous families with various types of MRX have now been studied by other investigators using molecular genetic techniques. In addition to the family described in this report, a number of these have demonstrated linkage to the DXYS1 locus. These data suggest that a gene for mental retardation may exist in the region of DXYS1. Alternatively, this area of the X-chromosome may harbor multiple different but closely linked genes which cause the various types of MRX.
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PMID:Linkage of nonspecific X-linked mental retardation to Xq21.31. 160 23

We report on a 10-year-old patient with the fragile X [fra(X)] syndrome and a 47,XXY karyotype. He had Martin-Bell syndrome, including typical craniofacial findings and mental retardation. The fra(X) was detected on both X chromosomes of the patient in 8% of the metaphases examined. DNA analysis using X-chromosome sequences from the pericentromeric region and from distal Xq suggests that the patient is homozygous at the fra(X) locus due to maternal nondisjunction during meiosis II.
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PMID:Origin of the supernumerary X chromosome in a patient with fragile X and Klinefelter syndrome. 167 17

We recently reported a new X-linked mental retardation (XLMR) disorder in a four-generation family of Dutch descent. Features included Dandy-Walker malformation, basal ganglia disease, and seizures. Twenty-six family members, including two living affected males and two obligate carriers, were available for study. No evidence of linkage was observed between the disease locus and RFLPs from several X-chromosome regions, including Xp21-p22 (13 markers), proximal Xq (four markers), and Xq28 (three markers). However, a new hypervariable short tandem repeat (STR) within the HPRT gene at Xq26 showed positive linkage to the disease locus, with a maximum lod score of 2.19 at a recombination fraction of 0. A second hypervariable marker in Xq26, the dinucleotide repeat XL90A3 (DXS425), showed a lod score of .84 at a recombination fraction of .11. Both the HPRT and DXS425 markers were typed in 40 CEPH families, and subsequent multipoint linkage analysis showed the following order: Xcen-DXS425-(HPRT,XLMR)-F9-qter. HPRT and these flanking markers are therefore useful for carrier detection and prenatal diagnosis in this family. This study illustrates that hypervariable STRs will be powerful tools for linkage analysis and genetic diagnosis, particularly when relatively small families are involved.
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PMID:Linkage of the gene for an X-linked mental retardation disorder to a hypervariable (AGAT)n repeat motif within the human hypoxanthine phosphoribosyltransferase (HPRT) locus (Xq26). 174 58

Laser microdissection has been used to dissect material from the X-chromosome region involved in fragile-X-linked mental retardation. After dissection, single chromosome slices corresponding to this fragile site were subjected to DNA amplification using either a vector ligation method (to provide known anchor sequences) or primer oligonucleotides corresponding to the ubiquitous Alu sequences. Amplified material was then cloned or, alternately, used to screen a gridded cosmid library. Eight cosmid clones identified in this way were regionally mapped using a panel of hybrid cell lines and shown to originate from a narrow interval centered on the fragile X site. Two clones are included in the approximately 6-cM interval defined by probes RNI (DXS369, 5 cM proximal) and VK21 (DXS 296, 1-2 cM distal) and which includes the fragile site, and at least one clone contains sequences conserved across species suggestive of a gene. This method combines the focused approach of microdissection and the convenience of obtaining cosmid (rather than small-insert) clones; it may be useful for studies of other defined chromosomal regions.
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PMID:Laser microdissection of the fragile X region: identification of cosmid clones and of conserved sequences in this region. 191 12

The prevalence of cutis verticis gyrata was studied in a psychiatric institutional population of 494 patients, the majority of whom were mentally retarded or had chronic schizophrenia. Twenty-two subjects (21 males and 1 female) were found to have primary cutis verticis gyrata, yielding a prevalence of about 4.5%. The frequency of the scalp disorder was 11.4% among mentally retarded patients and 1.7% in schizophrenic subjects. A cytogenetic study was performed on patients with primary cutis verticis gyrata. In 9 out of 21 subjects there was evidence of chromosomal fragile sites: 5 patients had fragile sites on the X-chromosome, in 2 there was fragility of chromosome 12 and in 2, fragility of chromosome 9. The fragile X-site is the genetic marker of the 'fragile X-syndrome', a sex-linked inherited disorder often associated with mental retardation and other neuropathological findings.
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PMID:Prevalence of primary cutis verticis gyrata in a psychiatric population: association with chromosomal fragile sites. 198 19

We studied 10 members of a 4 generation Missouri kindred with a dominant mental retardation syndrome with increasing severity in males. The 21 year-old propositus presented with severe mental retardation, microcephaly, asymmetric face, exotropia, hypogonadism, joint hypermobility, rocker bottom feet, and 10 low digital arches. Two brothers and a male cousin had similar features. The mother, sister, niece, maternal aunt, female cousin, and grandmother were examined and each had 8 to 10 low digital arches. Five of the women had exotropia and one had pes cavus feet. Chromosome analysis for fragile X in multiple relatives was normal. To determine the likelihood that this was an X-linked syndrome. DNA from relatives was hybridized to probes which detect 13 different loci spanning the X-chromosome. A peak LOD score of 2.78 at theta equal to 0.0 was calculated for the syndrome locus and DXYS1 (pDP34). The more distal Xq loci showed increasing recombination with the syndrome locus. These results are consistent with location for this syndrome near Xq21.31, the chromosomal locus for DXYSI.
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PMID:Unique X-linked mental retardation syndrome with fingertip arches and contractures linked to Xq21.31. 201 61

The study comprised two cases (male & female sibs) from one family, with Lesch-Nyhan Syndrome. They were subjected to clinical evaluation, pedigree construction, uric acid estimation in blood, urates in urine, metabolic screening of blood and urine for amino acids, examination of oral cavity, histological studies of the gingiva by light and electron microscopy as well as buccal smear for Barr & Y bodies (for the female). The proband, a six years old female presented with self-mutilation, mental retardation, hyperactivity and aggression. She had bitten her index finger causing amputation of its distal phalanx. On family study her younger brother (9 months) was found to have increased uric acid and less severe neurologic involvement. The serum uric acid level of the affected female was higher. Her Barr body showed normal pattern. Oral cavity examination showed no abnormalities. Histological examination of the gingiva showed macrophages around the blood vessels. Ultrastructural studies showed more or less normal epithelium. There was collection of macrophages around the blood vessels in the sub-epithelial layer, the cytoplasm of these macrophages contained stippled cytoplasmic inclusions. The surrounding connective tissue showed thin collagen fibers with sharp delineation between the epithelial and connective tissue layers indicating poor quality of collagen. There was no histological difference between the hemizygous male and the heterozygous female. The present study indicates heterozygous expression of Lesch-Nyhan Syndrome at both the clinical and the ultrastructural levels in favour of extreme lyonization or X-chromosome deletion in the affected female. Our findings also indicate that ultrastructural studies could be sensitive indicators of abnormal uric acid metabolism. Further studies are needed to compare the phenotypic expression of hemizygotes and heterozygotes with Lesch-Nyhan Syndrome at both the clinical and ultrastructural levels.
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PMID:Heterozygous expression of Lesch-Nyhan syndrome clinical and ultrastructural studies. 213 93

Glycerol kinase deficiency (GKD) has been described in isolation and in complex phenotypes including either congenital adrenal hypoplasia, Duchenne muscular dystrophy, or both. Cytogenetic and molecular studies have localized these defects to a deletion involving the X chromosome at band Xp21, consistent with its X-linked recessive pattern of inheritance. Other clinical findings in the complex glycerol kinase deficiency (CGKD) patients are mental retardation, short stature, and hypogonadotropic hypogonadism. We report on a 6-year-old boy who, in addition to the CGKD phenotype described above, had ocular hypopigmentation consistent with Forsius-Eriksson ocular albinism, also known as type 2 ocular albinism or Aland Island eye disease. Cytogenetic analysis shows an interstitial deletion in the short arm of the X-chromosome at Xp21.
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PMID:Aland Island eye disease (Forsius-Eriksson ocular albinism) and an Xp21 deletion in a patient with Duchenne muscular dystrophy, glycerol kinase deficiency, and congenital adrenal hypoplasia. 215 12

A gene map based on a compilation of genetic disorders involving mental retardation is presented. The presentation is divided into three parts; the first part describes 69 genes assigned to an autosome, the second part consists of the 73 genes assigned to the X-chromosome, and the third part consists of genetic disorders without any known chromosome location.
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PMID:Gene map of mental retardation. 232 18


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