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

We report on the prenatal diagnosis of two sib female fetuses with a satellited short arm of chromosome 4 and a male fetus with a satellited long arm of chromosome X. The first two fetuses had a cryptic balanced translocation (4;15)(p16;p11.1) inherited from a mother carrying a satellited 4p and having an affected child with the Wolf-Hirschhorn syndrome. The third fetus had a satellited Xq, with a deletion of subtelomeric region of Xq. The mother was subsequently found to have the same satellited Xq but without the presence of a reciprocal translocation. She decided to continue the pregnancy. The proband with a satellited Xq manifested developmental delay, mental retardation, hypertelorism, ptosis of one eye, low-set ears, and hearing disturbance at age 6 months. Fluorescence in situ hybridization (FISH) with a specific telomeric or subtelomeric probe, and genetic marker analyses were used to confirm the diagnosis. Pregnant women with satellited non-acrocentric chromosomes are at risk for carrying fetuses with chromosome abnormalities. If the X chromosome is involved, the fetuses can be affected with X-linked recessive disorders including mental retardation. Detailed genetic counselling, cytogenetic studies, FISH and genetic marker analyses are useful in prenatal detection of abnormal chromosome rearrangements.
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PMID:Prenatal diagnosis of inherited satellited non-acrocentric chromosomes. 1082 Apr 5

A case of juvenile neuronal ceroid lipofuscinosis (JNCL) diagnosed on the basis of clinical features, electrophysiologic studies and skin electron microscopy is reported. JNCL was suspected on the basis of characteristic symptoms including progressive loss of vision, seizures, mental retardation and motor disabilities. Diagnosis was confirmed by neurophysiological and biopsy studies. The disease is caused by 23 different mutations in a gene recently isolated on chromosome 16 p11.2-12.1. Although universally fatal, characterisation of mutations can help in prenatal diagnosis in future pregnancies.
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PMID:Juvenile neuronal ceroid lipofuscinosis. 1102 25

Mental retardation is a very common and extremely heterogeneous disorder that affects about 3% of the human population. Its molecular basis is largely unknown, but many loci have been mapped to the X chromosome. We report on two mentally retarded females with X;autosome translocations and breakpoints in Xp11, viz., t(X;17)(p11;p13) and t(X;20)(p11;q13). (Fiber-) FISH analysis assigned the breakpoints to different subbands, Xp11.4 and Xp11.23, separated by approximately 8 Mb. High-resolution mapping of the X- chromosome breakpoints using Southern blot hybridization resulted in the isolation of breakpoint-spanning genomic subclones of 3 kb and 0. 5 kb. The Xp11.4 breakpoint is contained within a single copy sequence, whereas the Xp11.23 breakpoint sequence resembles an L1 repetitive element. Several expressed sequences map close to the breakpoints, but none was found to be inactivated. Therefore, mechanisms other than disruption of X-chromosome genes likely cause the phenotypes.
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PMID:Molecular cloning of Xp11 breakpoints in two unrelated mentally retarded females with X;autosome translocations. 1106 Apr 62

We describe a family in which non-syndromic mental retardation (MR) and an apparently balanced reciprocal translocation, t(1;17)(p36. 3;p11.2) segregates in eight individuals over three generations. Four children showed psychomotor developmental delay, reduced muscle tone, poor coordination, and learning difficulties. The affected adults had a varying range of behavioral problems and difficulties in social adjustment but no abnormal neurological signs. Most of them were functioning at the borderline learning difficulty level in intellectual abilities with additional specific difficulties in reading in two individuals. The Smith-Magenis and 1p36.3 deletion syndromes were excluded. We propose that this reciprocal translocation has disrupted an autosomal gene with an important function in cognitive development, and this family represents a unique resource for the molecular genetic study on non-syndromic MR.
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PMID:Non-syndromic mental retardation segregating with an apparently balanced t(1;17) reciprocal translocation through three generations. 1107 57

In five families with questionable chromosome rearrangements, we identified an interchromosomal insertion by fluorescent in situ hybridization (FISH). In case 1 with a dir ins (5;11)(p14;q14q24) in three generations, the mentally retarded and microcephalic proband showed a 5p14-->pter deletion. In case 2, a duplication (13)(q21.31--> q31.2) combined with a deletion (11)(q14-->q22) segregated from a reciprocal ins(11;13)(q14q122)(q21.32q31.2), causing a mixed phenotype with psychomotor retardation, caput quadratum, choanal atresia, and pes equinovarus. In case 3, a dir ins (18;5)(q21.3;p13.1p14) was associated with spontaneous abortions, in case 4, the proband with mental retardation, microcephaly, and a heart defect showed a pure trisomy of (12)(q13-->q15), which had segregated from a carrier of an ins (18;12)(p11.3;q13q15). In case 5, a duplication of (10)(q26.3-->q25.2) segregated from an inv ins(5;10)(q15;q26.3q25.2), which was passed on directly from a mother to her son,with mental retardation. In all families the elucidation of the insertional translocation (IT) considerably increased the associated genetic risks of carriers. For the review, we collected data from 81 articles on 87 IT probands on ascertainment, origin, familial transmittance, progeny, and genetic risks of IT carriers. We also discussed the recombinant chromosomes and complex rearrangements associated with ITs, and listed chromosome regions occurring solely as deletions, or solely as duplications, or as both to facilitate genotype/phenotype correlations. We conclude that ITs are rare chromosomal rearrangements with an 1:80,000 incidence, of which nearly 80% were referred because of congenital abnormalities and mental retardation. A maternal origin was seen in 59.5%, a paternal origin in 26.6%, and 13.9% were de novo. No notable difference in fertility between male and female IT carriers was noticed. Bias of ascertainment was excluded in 15 familial cases and led to an estimate of the genetic risks for IT carriers of 32.0-36.0%. The mean size of the inserted regions occurring solely as duplications (n=39) measures 0.96% of the haploid autosomal length (HAL), and of regions solely occurring as deletions (n=14) 0.47% HAL. In the families where both aneusomies occurred, the size of the insertions ranged between 0.22 and 1.21% HAL. Overall, the findings fit with the general idea that a surplus of genetic material is tolerated more easily than a deficiency.
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PMID:Interchromosomal insertions. Identification of five cases and a review. 1114 Sep 39

We evaluated a kindred with X-linked mental retardation and epilepsy. Seven affected males with mild to moderate mental retardation developed seizures (primarily generalized, tonic-clonic, and atonic) that began on average at 6.8 months of age (range, 4 to 14 months). These patients did not have a history of infantile spasms. There were no dysmorphic features. Other than mental retardation, the neurological examination was unremarkable, with exception of 2 affected subjects who had mild generalized rigidity and ataxia. We identified tight linkage to a group of markers on Xp21.1-p11.4. A maximum two-point LOD score of +3.83 at straight theta = 0 was obtained for markers DXS8090, DXS1069, DXS8102, and DXS8085. This locus spans 7.7cM between DXS1049 and DXS8054 and does not overlap the locus for X-linked West syndrome. The tetraspanin gene, implicated in nonspecific mental retardation, is mapped to this region. We sequenced the tetraspanin coding sequence in subjects with X-linked mental retardation and epilepsy and did not identify disease-specific mutations. The syndrome we describe, designated X-linked mental retardation and epilepsy, is clinically and genetically distinct from X-linked West syndrome and other X-linked mental retardation-epilepsy syndromes.
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PMID:Novel mental retardation-epilepsy syndrome linked to Xp21.1-p11.4. 1178 83

Non-syndromic X linked mental retardation (MRX) is a heterogeneous group of conditions in which all patients have mental retardation as the only constant phenotypic feature. We have identified a female patient with mental retardation and a balanced translocation involving chromosomes X and 21, t(X;21)(p11.2;q22.3). Physical mapping of the translocation breakpoint on the human X chromosome was performed using fluorescence in situ hybridisation. We have mapped the X chromosome breakpoint to a 21 kb DNA fragment upstream of the first exon of the KLF8 (ZNF741) gene in Xp11.21. We have subsequently shown that the KLF8 transcript is no longer detected in cells from the patient, although KLF8 expression is otherwise normally present in control lymphoblasts. Mutation screening of probands from 20 unrelated XLMR families linked to the proximal short arm of the human X chromosome failed to show any mutation in the coding region of the KLF8 gene.
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PMID:Abnormal expression of the KLF8 (ZNF741) gene in a female patient with an X;autosome translocation t(X;21)(p11.2;q22.3) and non-syndromic mental retardation. 1183 60

Smith-Magenis syndrome (SMS) is a multiple congenital anomalies/mental retardation syndrome associated with an interstitial deletion of chromosome 17 involving band p11.2. SMS is hypothesised to be a contiguous gene syndrome in which the phenotype arises from the haploinsufficiency of multiple, functionally-unrelated genes in close physical proximity, although the true molecular basis of SMS is not yet known. In this study, we have generated the first overlapping and contiguous transcription map of the SMS critical interval, linking the proximal 17p11.2 region near the SMS-REPM and the distal region near D17S740 in a minimum tiling path of 16 BACs and two PACs. Additional clones provide greater coverage throughout the critical region. Not including the repetitive sequences that flank the critical interval, the map is comprised of 13 known genes, 14 ESTs, and six genomic markers, and is a synthesis of Southern hybridisation and polymerase chain reaction data from gene and marker localisation to BACs and PACs and database sequence analysis from the human genome project high-throughput draft sequence. In order to identify possible candidate genes, we performed sequence analysis and determined the tissue expression pattern analysis of 10 novel ESTs that are deleted in all SMS patients. We also present a detailed review of six promising candidate genes that map to the SMS critical region.
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PMID:Genomic organisation of the approximately 1.5 Mb Smith-Magenis syndrome critical interval: transcription map, genomic contig, and candidate gene analysis. 1184 Jan 90

In this paper we present the case of a girl at the age of 32 months with dysmorphic features, including general muscular hypotonia, developmental delay and mental retardation. The cytogenetic analysis revealed de novo partial duplication of Xp: 46,X,dup(X)(p11.23-->p22.33: :p11.23-->p22.33). To characterize the duplication, X painting, Kallman (KAL), yeast artificial chromosomes (YACs) and bacterial artificial chromosomes (BACs) covering Xp11.23-->Xp22.33 region were used. Selective inactivation of the abnormal X chromosome using HpaII digestion of the AR gene was evident. After BrdU incorporation the abnormal X was late-replicating in all lymphocytes examined. There was one peculiar exception observed: the break-point region was consistently early replicating. The replicating pattern of this region corresponded to the active X chromosome. Methylation pattern of late replicating X chromosome was studied also using antibodies against 5-methylcytosine. The pattern corresponded to the normally inactive X chromosome, with the exception of the previously observed break-point region which revealed an early replicating pattern with strong fluorescent signal, similar to the pattern of the active X chromosome. The observed phenomenon could lead to the abnormal phenotype of the patient, with some normally inactive genes of the break-point region escaping the inactivation process. The abnormal clinical findings could also be due to tissue-dependent differences in the inactivation pattern.
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PMID:Partial Xp duplication in a girl with dysmorphic features: the change in replication pattern of late-replicating dupX chromosome. 1190 57

Cutis marmorata telangiectatica congenita (CMTC) is a rare cutaneous disorder. More than one half of the patients with CMTC have additional extra-cutaneous associated congenital anomalies. A subset of patients with CMTC have macrocephaly, the M-CMTC syndrome. This is a report on a patient with the M-CMTC syndrome and a de novo translocation t(2;17)(p11;p13). The etiology and pathology of the M-CMTC syndrome is unknown. Suggestions for the cause for M-CMTC include the occurrence of a new dominant mutation in a single gene, deletion of multiple contiguous genes at a level beyond the resolution of conventional karyotyping and chromosomal mosaicism. This patient did not have chromosomal mosaicism, however he had a translocation. It can be postulated that in the present patient the translocation breakpoints disrupted one or more genes entailing skin lesions but also other features: mental retardation, macrocephaly and facial dysmorphia.
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PMID:Macrocephaly-cutis marmorata telangiectatica congenita: report of a patient with a translocation. 1287 11


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