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)

A de novo partial 13q monosomy is reported in a severely affected 8-year-old female with the karyotype 46,XX,del(13)(q32). Abnormal features included mental retardation, delayed development, microcephaly, encephalocele, hearing loss, hypertelorism, ptosis, flat nasal bridge, protruding upper incisors, facial asymmetry, short neck, hypoplastic thumbs, scoliosis and clubfeet. The deletion was demonstrable by R-banding but was not apparent by GTG banding. The locus for esterase D (EC 3.1.1.1) is excluded from the deleted segment 13q32 leads to 13qter.
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PMID:Long arm deletion of chromosome 13 with exclusion of esterase D from 13q32 leads to 13qter. 739 15

A 1-year-old male infant was found to have a de novo unbalanced translocation, resulting in trisomy for a portion of the short arm of chromosome 3, i.e. 46,XY,der(7)t(3;7) (p24.1;p22). Previous cases with a so-called "trisomy 3p syndrome" were evaluated by GTG banding, while we attempted to characterize the present case by the FISH-technique. The major clinical features included: dysmorphic ears, decreased muscle tone and seizure episodes associated with fever, which are concordant with "trisomy 3p syndrome". The most common malformations of trisomy 3p syndrome are: psychomotor and mental retardation, short neck, hypertelorism/telecanthus and congenital heart defects. Predominantly, the 3p trisomies have been maternally derived and the major mechanism of inheritance is due to a malsegregation of the chromosomes that are involved in a parental balanced translocation. A review of 44 cases from 35 studies revealed that the clinical manifestations have been quite varied, depending upon the amount of 3p2 material in the trisomic state, but interestingly a recognizable pattern of features was obvious in those cases whose cytogenetic findings and clinical histories were known.
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PMID:Molecular characterization of trisomic segment 3p24.1-->3pter: a case with review of the literature. 758 45

We have identified a new mutation of Norrie disease (ND) gene in two Japanese males from unrelated families; they showed typical ocular features of ND but no mental retardation or hearing impairment. A mutation was found in both patients at the initiation codon of exon 2 of the ND gene (ATG to GTG), with otherwise normal nucleotide sequences. Their mothers had the normal and mutant types of the gene, which was expected for heterozygotes of the disease. The mutation of the initiation codon would cause the failure of ND gene expression or a defect in translation thereby truncating the amino terminus of ND protein. In view of the rarity and marked heterogeneity of mutations in the ND gene, the present apparently unrelated Japanese families who have lived in the same area for over two centuries presumably share the origin of the mutation.
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PMID:Novel mutation at the initiation codon in the Norrie disease gene in two Japanese families. 781 11

We report on a 4 year-old girl with a 1p36.3-pter deletion. Clinical findings included minor anomalies of face and distal limbs, patent ductus arteriosus, the Ebstein heart anomaly, and brain atrophy with seizures. Conventional GTG-banded chromosome analysis revealed a normal (46,XX) result. Subsequent analysis by fluorescent in situ hybridization (FISH) using distal probes demonstrated a deletion of 1p36.6-pter. Molecular investigations with microsatellite markers showed hemizygosity at three loci at 1p36.3 with loss of the paternal allele. The deletion of 1p36.3 is difficult to identify by banding alone; indeed, our patient represents the third reported case with a del(1)(p36.3) that was detected only after more detailed analysis. In all three cases the deletion was detected through screening of patients with multiple congenital anomalies/mental retardation syndromes suggestive of autosomal chromosome aberrations for subtelomeric submicroscopic deletions by means of FISH or microsatellite marker analysis. On the basis of these observations we highly recommend that FISH with a subtelomeric 1p probe be routinely performed in patients with similar facial phenotype, severe mental retardation and seizures, and a heart malformation, particularly the Ebstein anomaly.
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PMID:Terminal deletion, del(1)(p36.3), detected through screening for terminal deletions in patients with unclassified malformation syndromes. 1056 88

We present two brothers with mental retardation, seizures disorder, generalized muscular hypertonia, kyphoscoliosis, minor anomalies and a prominent midface. GTG-banded chromosome analysis showed a derivative chromosome 14 without clues toward the origin of the rearrangement. Microdissection of the derivative chromosome 14 and subsequent reverse painting demonstrated partial trisomy 7q32-q34 as the unbalanced product of a maternal insertion (14;7). Thus, we identified two cases with pure trisomy 7q32-q34 that allowed further delineation of this aneusomy syndrome.
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PMID:Mental and psychomotoric retardation in two brothers with pure partial trisomy 7q32-q34 due to a maternal insertion (14;7). 1076 86

The neural cell adhesion molecule L1 mediates the axon outgrowth, adhesion, and fasciculation necessary for proper development of synaptic connections. Mutations of human L1 cause an X-linked mental retardation syndrome termed CRASH (corpus callosum hypoplasia, retardation, aphasia, spastic paraplegia, and hydrocephalus), and L1 knock-out mice display defects in neuronal process extension resembling the CRASH phenotype. Little is known about the biochemical or cellular mechanism by which L1 performs neuronal functions. Here it is demonstrated that clustering of L1 with antibodies or L1 protein in rodent B35 neuroblastoma and cerebellar neuron cultures induced the phosphorylation/activation of the mitogen-activated protein kinases (MAPKs) and extracellular signal-regulated kinases 1 and 2. MAPK activation was essential for L1-dependent neurite outgrowth, because chemical inhibitors [2-(2'-amino-3'-methoxyphenyl)-oxanaphthalen-4-one and 1,4-diamino-2, 3-dicyano-1,4-bis(2-aminophenylthio)butadiene] of the MAPK kinase MEK strongly suppressed neurite outgrowth by cerebellar neurons on L1. The nonreceptor tyrosine kinase pp60(c-src) was required for L1-triggered MAPK phosphorylation, as shown in src-minus cerebellar neurons and by expression of the kinase-inactive mutant Src(K295M) in B35 neuroblastoma cells. Phosphatidylinositol 3-kinase (PI3-kinase) and the small GTPase p21(rac) were identified as signaling intermediates to MAPK by phosphoinositide and Rac-GTP assays and expression of inhibitory mutants. Antibody-induced endocytosis of L1, visualized by immunofluorescence staining and confocal microscopy of B35 cells, was blocked by expression of kinase-inactive Src(K295M) and dominant-negative dynamin(K44A) but not by inhibitors of MEK or PI3-kinase. Dynamin(K44A) also inhibited L1 antibody-triggered MAPK phosphorylation. This study supports a model in which pp60(c-src) regulates dynamin-mediated endocytosis of L1 as an essential step in MAPK-dependent neurite outgrowth on an L1 substrate.
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PMID:A MAP kinase-signaling pathway mediates neurite outgrowth on L1 and requires Src-dependent endocytosis. 1081 53

Mental retardation (MR) is one of the most common human disorders. MR may be just one of the clinical signs of a complex syndrome or it may be associated with metabolic disorders or with disorders of brain development, but in many patients [nonspecific MR (NSMR)], it is the only consistent clinical manifestation. It is expected that NSMR is caused by alterations in molecular pathways important for cognitive functions. Insights into NSMR have recently come from the study of X-linked MR as eight genes were identified during the last few years. This development has represented a fundamental breakthrough in our understanding of NSMR and of cognitive functions and has opened new perspectives in the study of MR. The new genes identified are a heterogeneous group, but it is very intriguing that they are all directly or indirectly involved in signaling pathways and that the majority are proteins that regulate members of the Ras superfamily of small GTP binding proteins.
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PMID:In search of the MRX genes. 1144 91

The etiology of mental retardation (MR), often presenting as developmental delay in childhood, is unknown in approximately one-half of cases. G-banding is the standard method for investigating those suspected of having a chromosomal etiology; however, detection of structural abnormalities is limited by the size and pattern of the G-bands involved. Rearrangements involving subtelomeric regions have been shown to cause MR and this has generated interest in investigating the prevalence of these rearrangements using telomere-specific probes. In addition, because cryptic interchromosomal rearrangements may not be small or confined to chromosomal ends, spectral karyotyping (SKY) using chromosome-specific painting probes may be of value. We report here a study using these two FISH-based techniques in 50 children with idiopathic MR or developmental delay and normal GTG-banded karyotypes. Our objective was to assess the prevalence of cryptic rearrangements in this population using subtelomeric FISH and SKY. Three rearrangements were detected by subtelomeric FISH: a derivative 5 from a maternal t(5;21); a recombinant 11 from a paternal pericentric inversion; and a 2q deletion that was also present in the mother. Only the derivative 5 was detected by SKY. SKY did not detect any interstitial interchromosomal rearrangement. The prevalence of clinically significant cryptic rearrangements by subtelomeric FISH and SKY was thus 4% (95% confidence interval 0.5-13.7) and 2% (95% CI 0.05-10.7), respectively. This study supports the view that G-banding does not detect all clinically significant chromosomal abnormalities and that subtelomeric FISH and SKY can detect some of these abnormalities.
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PMID:Detecting rearrangements in children using subtelomeric FISH and SKY. 1184 Apr 82

A girl with psychomotor retardation and a pattern of minor anomalies was found to have a slightly enlarged short arm of chromosome 18 by conventional GTG-banded chromosome examination. The 18p+chromosome has also been found in the father. FISH studies using chromosome 18-and chromosome 20-specific painting probes confirmed a reciprocal whole arm translocation between chromosomes 18 and 20 in the father, resulting in monosomy of the short arm of chromosome 18 and trisomy of the short arm chromosome 20 in the patient. FISH analysis using a chromosome 18 alpha-satellite-specific probe showed a reduced signal intensity. The patient presented with a flat, oval face, upslanting palpebral fissures, periorbital fullness, and mental retardation; she also had chronic diarrhea with milk protein intolerance and juvenile rheumatoid arthritis at age 5 years. Juvenile rheumatoid arthritis, like several other immunologic disorders, has occasionally been reported in patients with deletion of 18p, and thus most likely loss of a gene or genes on 18p is responsible for various immunologic disorders occurring in these patients.
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PMID:Patient with rheumatoid arthritis and MCA/MR syndrome due to unbalanced der(18) transmission of a paternal translocation t(18;20)(p11.1;p11.1). 1189 91

Recent studies have shown that cryptic unbalanced subtelomeric rearrangements contribute to a significant proportion of idiopathic syndromic mental retardation cases. Using a fluorescent genotyping based strategy, we found a 10% rate of cryptic subtelomeric rearrangements in a large series of 150 probands with severe idiopathic syndromic mental retardation and normal RHG-GTG banded karyotype. Fourteen children were found to carry deletions or duplications of one or more chromosome telomeres and two children had uniparental disomy. This study clearly shows that fluorescent genotyping is a sensitive and cost effective method that not only detects cryptic subtelomeric rearrangements but also provides a unique opportunity to detect uniparental disomies. We suggest giving consideration to systematic examination of subtelomeric regions in the diagnostic work up of patients with unexplained syndromic mental retardation.
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PMID:Automated fluorescent genotyping detects 10% of cryptic subtelomeric rearrangements in idiopathic syndromic mental retardation. 1195 Aug 56


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