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Query: UMLS:C0917816 (mental retardation)
 15,867 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Non-random tumour-specific chromosomal abnormalities have been observed in cells of many different human tumours. In Wilms' tumour (WT) and retinoblastoma, a chromosomal deletion occurs germinally or somatically and has been considered an important step in tumour development. One class of potential cellular transforming genes comprises the cellular homologues of the transforming genes of highly oncogenic retroviruses. A remarkable concordance between the chromosomal location of human cellular oncogenes and the breakpoints involved in acquired chromosomal translocations is becoming apparent in various cancers: the oncogenes c-mos, c-myc and c-abl are located at the breakpoints that occur in acute myeloblastic leukaemia, Burkitt's lymphoma and chronic myelocytic leukaemia respectively. Thus when the oncogene c-Ha-ras1 was localized to the short arm of human chromosome 11 (refs 6-8; region 11p11 leads to p15 and not 11p13 as stated in ref. 5), it was proposed as a possible aetiological agent in the aniridia-WT association (AWTA) that results from a deletion of 11p13 (although a transforming gene recently isolated from a WT cell line (G401) was shown not to be homologous to either c-Ha-ras or c-Ki-ras9). We have now looked for deletion or rearrangement of c-Ha-ras1 in the DNA from four subjects with del(11p13)-associated predisposition to Wilms' tumour, aniridia, genitourinary abnormalities and mental retardation. We report here that in no case is c-Ha-ras1 deleted, and we have further refined its location to 11p15.1 leads to 11p15.5. On the basis of enzyme studies and direct gene dosage determination for c-Ha-ras1 and beta-globin in neoplastic and non-neoplastic tissues from one patient, we conclude that deletion of the normal counterpart of 11p cannot account for the development of the tumour.
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PMID:c-Ha-ras1 is not deleted in aniridia-Wilms' tumour association. 631 28

A del(13)(q13q21.1) was found in a patient with bilateral retinoblastoma and mental retardation. The father was carrier of an ins(16;13)(q12.2;q13q21.1) which also was present in several other family members, and responsible for another case of del (13q)-retinoblastoma and two cases of trisomy for the inserted segment. This second del(13q) patient was also carrier of a balanced t(11;22).
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PMID:Two cases of del(13q)-retinoblastoma and two cases of partial trisomy due to a familial insertion. 631 32

One of the most provocative findings in tumour biology is the relationship between chromosomal changes and embryonal cancers in children. For example, children with the rare paediatric syndrome AGR triad (aniridia, genito-urinary abnormalities and mental retardation) often develop Wilms' tumours at a very early age and carry a germ-line deletion on the short arm of chromosome 11 (11p13). It has been suggested that the germ-line deletion 11p is the first of two or more steps to cancer in AGR children. If this were true, one might expect a similar deletion to arise somatically in the far more common isolated Wilms' tumours of children without AGR, as suggested by Knudson from epidemiological data. However, a chromosomal deletion on 11p was observed in only two of five such cases, while it was absent or seen inconsistently in others. We have now used a molecular genetic approach to determine whether Wilms' tumour cells possess somatic alterations at 11p loci. We have found somatic deletions of specific genes in four of six Wilms' tumours. Surprisingly, in all four cases, the deletions were associated with duplications leading to homozygosity of the non-deleted alleles in the tumour cells. As analogous observations were recently reported in retinoblastoma, the genetic events reported here may underlie the development of many such embryonal tumours in children.
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PMID:Somatic deletion and duplication of genes on chromosome 11 in Wilms' tumours. 632 39

To our knowledge, 20 cases of retinoblastoma associated with a chromosome #13 aberration have been reported. The present study utilized high-resolution prophase banding analysis of 12 additional retinoblastoma patients to determine the occurrence of chromosome aberrations and identify consistently associated clinical abnormalities. Six male and six female patients were studied representing seven cases of bilateral and five cases of unilateral retinoblastoma. One case of unilateral and two cases of bilateral retinoblastoma and detectable cytogenetic abnormalities, all involving an interstitial deletion of 13q14 on the long arm of one chromosome #13. In all five unilateral cases the tumor manifested in the left orbit, and in all seven bilateral cases the left eye was at a more malignantly advanced stage than the right eye. All three cases with a chromosome abnormality had varying degrees of developmental and/or mental retardation, along with at least one other congenital abnormality. In addition to the 12 cases of retinoblastoma, a patient with severe ophthalmologic abnormalities and mild congenital anomalies was studied by the prophase banding technique and found to be partially trisomic for the 13q14 region with gene loci for optic development and indicate that cytogenetic abnormalities may occur even more frequently in retinoblastoma than indicated by the small number of cases reported in the literature.
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PMID:Retinoblastoma and its association with a deletion in chromosome #13: a survey using high-resolution chromosome techniques. 710 85

Two cases of association of unilateral and bilateral retinoblastoma, respectively, with interstitial deletions of long arms of chromosome 13 are presented. The clinical pictures of both children corresponded to the moderate extent of the deletions, with both somatic and mental retardation in both children, and mild phenotypic manifestations (hypertelorism, slight epicanthi, mild facial hirsutism, and partial syndactyly in the child with unilateral retinoblastoma). Opinions concerning the association of chromosome 13 deletion with retinoblastoma are discussed.
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PMID:Retinoblastoma and chromosome 13 deletion. 716 Nov 17

A partial monosomy 13 by interstitial deletion was found in the complement of a patient with mental retardation and mild dysmorphic features. Due to the involvement of band q14 in the deletion, an ocular investigation was performed which showed the presence of a retinoblastoma in a preclinical stage. The different patterns of retinoblastoma inheritance are discussed and the importance of an accurate clinical investigation is stressed in all cases in whom chromosomal aberration is known to be associated with neoplasias.
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PMID:Chromosome 13 deletion syndrome: report of a new case and discussion of the different etiologic patterns of retinoblastoma. 724 83

The outcomes for five patients with retinoblastoma and constitutional chromosomal abnormalities involving the long arm of chromosome 13 are reported. All patients demonstrated developmental delay and mental retardation. Four of these patients are alive 23, 21, 15, and 1 year from diagnosis; one died of pneumonia with septicemia. Each of the four survivors has, with aging, shown hypotonia, mutism, contractures, and inability to function independently.
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PMID:Outcome for patients with constitutional 13q chromosomal abnormalities and retinoblastoma. 782 49

The Wilms tumour (WT1) gene was first localized through its deletion in individuals with the WAGR syndrome (Wilms tumour, aniridia, genitourinary abnormalities and mental retardation). Such individuals have a 30-50% lifetime risk of developing Wilms tumour and carry constitutional interstitial deletions of chromosome 11p13, including the WT1 gene. Second primary tumours occurring in such individuals might also be related to their genetic predisposition to cancer, as shown for hereditary retinoblastoma. We have found a mutation in the zinc finger region of the remaining WT1 allele in a case of acute myeloid leukaemia developing in a Wilms tumour survivor with the WAGR syndrome. This mutation would be predicted to disrupt DNA binding by this developmentally regulated transcription factor. This finding implicates the WT1 gene in the regulation of myelopoiesis and suggests that WT1 mutations may be found in some sporadic leukaemias.
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PMID:The Wilms tumour (WT1) gene is mutated in a secondary leukaemia in a WAGR patient. 783 22

In screens for genetic modifiers of lin-35/Rb, the C. elegans retinoblastoma protein (Rb) homolog, we have identified a mutation in xnp-1. Mutations in xnp-1, including a presumed null allele, are viable and, in general, appear indistinguishable from the wild type. In contrast, xnp-1 lin-35 double mutants are typically sterile and exhibit severe defects in gonadal development. Analyses of the abnormal gonads indicate a defect in the lineages that generate cells of the sheath and spermatheca. xnp-1 encodes the C. elegans homolog of ATR-X, a human disease gene associated with severe forms of mental retardation and urogenital developmental defects. xnp-1/ATR-X is a member of the Swi2/Snf2 family of ATP-dependent DEAD/DEAH box helicases, which function in nucleosome remodeling and transcriptional regulation. Expression of an xnp-1 Colon, two colons GFP promoter fusion is detected throughout C. elegans development in several cell types including neurons and cells of the somatic gonad. Our findings demonstrate a new biological role for Rb family members in somatic gonad development and implicate lin-35 in the execution of multiple cell fates in C. elegans. In addition, our results suggest a possible conserved function for xnp-1/ATR-X in gonadal development across species.
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PMID:lin-35/Rb and xnp-1/ATR-X function redundantly to control somatic gonad development in C. elegans. 1532 17

Constitutional chromosome deletions can predispose to the development of cancer with the phenotypic characteristics of inherited cancer syndromes, when the deleted region encompasses a tumour suppressor gene. Examples of such conditions are represented by the cytogenetic deletions associated with retinoblastoma, Wilms tumour and familial adenomatous polyposis. So far, no constitutional deletions involving the genes implicated in hereditary non-polyposis colorectal cancer (HNPCC) have been identified. This may be at least partially because of the lack of distinctive phenotypic manifestations in HNPCC. We describe the first case of a constitutional microdeletion associated with HNPCC. Suspicion of a microdeletion was prompted by the association of mental retardation, postnatal growth deficiency, minor congenital anomalies and early onset (37 years) sporadic colon cancer. The patient was found to harbour a microdeletion within chromosome 2p16-p21, including the MSH2 gene. Since there are very few reports of deletions of the 2p16-p21 region, our observation sets the grounds for the definition of a novel multiple congenital anomaly/mental retardation/cancer microdeletion syndrome.
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PMID:A novel microdeletion syndrome with loss of the MSH2 locus and hereditary non-polyposis colorectal cancer. 1567 31


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