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

X-linked hydrocephalus and the X-linked MASA syndrome (Mental retardation. Adducted thumbs, Shuffling gait and Aphasia) both have a variable clinical spectrum with great overlap. Data from DNA linkage analysis placed the locus for both conditions at Xq28. On clinical and molecular grounds it has been hypothesized that both MASA syndrome and X-linked hydrocephalus are caused by a mutation in the same gene at Xq28. There is no significant clinical marker in the obligate female carriers and prenatal diagnosis by ultrasound is not reliable; DNA analysis can offer an improved genetic counseling for the families and more reliable prenatal diagnosis. In the gene encoding for Ll, a neural cell adhesion molecule and located at Xq28, several different mutations have been reported in X-linked hydrocephalus families and in a MASA family. We report data on DNA linkage analysis in 6 families with X-linked hydrocephalus/MASA syndrome. These data illustrate the importance of DNA linkage analysis in the individual family; they also show, however, the problem of studying small families. Genetic heterogeneity cannot be excluded.
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PMID:The spectrum of "complicated spastic paraplegia, MASA syndrome and X-linked hydrocephalus". Contribution of DNA linkage analysis in genetic counseling of individual families. 803 29

The MASA syndrome is an X-linked disorder with mental retardation, spastic paraparesis, and adducted thumbs as the most characteristic features. We performed linkage analysis, using Xq28 markers, on a large MASA syndrome family. The maximum lodscore was 6.37 at 0 recombination for DXS52 and 5.99 at 0 recombination for DXS305. Crossovers were demonstrated between the disorder and DXS455. Clinical and linkage data from this family further support the hypothesis that the MASA syndrome and X-linked hydrocephalus are allelic disorders.
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PMID:Fine mapping of X-linked clasped thumb and mental retardation (MASA syndrome) in Xq28. 806 32

MASA syndrome includes mental retardation, adducted thumbs, shuffling gait and aphasia or speech delay. MASA syndrome, X-linked hydrocephalus and X-linked spastic paraplegia have been linked to the same markers on Xq28 and perhaps represent variation in the clinical expression of the same gene or manifestations of different mutant alleles. The present family includes five males in two generations with borderline to mild mental retardation (5/5), speech delay (5/5), spastic paraplegia (5/5), adducted thumbs (2/5) and marked hydrocephalus (1/5). Of these males, four were evaluated by MRI or CT scan and all four were determined to have partial to complete agenesis of the corpus callosum (ACC). DNA studies confirm linkage to Xq28 probe St14 (DXS52) with a lod score of 2.86 and no recombination. It is not known if X-linked ACC is linked to the same Xq28 region.
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PMID:Agenesis of the corpus callosum associated with MASA syndrome. 830 64

L1 is a neuronal cell adhesion molecule with important functions in the development of the nervous system. The gene encoding L1 is located near the telomere of the long arm of the X chromosome in Xq28. We review here the evidence that several X-linked mental retardation syndromes including X-linked hydrocephalus (HSAS), MASA syndrome, X-linked complicated spastic paraparesis (SP1) and X-linked corpus callosum agenesis (ACC) are all due to mutations in the L1 gene. The inter- and intrafamilial variability in families with an L1 mutation is very wide, and patients with HSAS, MASA, SP1 and ACC can be present within the same family. Therefore, we propose here to refer to this clinical syndrome with the acronym CRASH, for Corpus callosum hypoplasia, Retardation, Adducted thumbs, Spastic paraplegia and Hydrocephalus.
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PMID:CRASH syndrome: clinical spectrum of corpus callosum hypoplasia, retardation, adducted thumbs, spastic paraparesis and hydrocephalus due to mutations in one single gene, L1. 855 2

The cell adhesion molecule L1 plays an important role in neural development. We have previously demonstrated that the second immunoglobulin-like domain (Ig2) of L1 contains both homophilic binding and neuritogenic activities (Zhao, X., and Siu, C.-H. (1995) J. Biol. Chem. 270, 29413-29421). Recently, two mutations (R184Q and H210Q) within the Ig2 region of the human L1 gene have been shown to be responsible for X-linked hydrocephalus and the related MASA (mental retardation, aphasia, shuffling gait, and adducted thumbs) syndrome. Glutathione S-transferase-Ig2 fusion proteins containing these mutations were used to evaluate their effects on L1. The homophilic binding activity of fusion proteins and their ability to promote neurite outgrowth from retinal cells were examined. The R184Q mutation led to a complete loss of both homophilic binding and neuritogenic activities, while the H210Q mutation resulted only in a partial loss. These results provide, for the first time, direct demonstration of the deleterious effects of hydrocephalus/MASA mutations on two intrinsic properties of L1.
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PMID:Differential effects of two hydrocephalus/MASA syndrome-related mutations on the homophilic binding and neuritogenic activities of the cell adhesion molecule L1. 863 66

Two patients with X-chromosomal hydrocephalus internus (aqueduct stenosis, clasped thumbs, mental retardation and spasticity) habe been described. In both cases the family history revealed further affected relatives. The intra- and interfamilial variability of this rare X-chromosomal recessive disease will be demonstrated. In this context differentialdiagnoses like X-linked MASA syndrome and X-linked spastic paraplegia have been discussed on the basis of a variable expressivity of different mutations in the same gene.
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PMID:[X-chromosomal recessive hydrocephalus internus: a separate disease picture? 2 further case reports and review of the literature]. 867 3

Familial spastic paraplegia (FSP or SPG) is a genetically heterogeneous group of upper motor neuron syndromes. To date, two distinct loci for X-linked recessive type (SPG1 and SPG2), three loci for autosomal dominant type (FSP1, FSP2 and FSP3), and one locus for autosomal recessive type have been reported. SPG1 and SPG2 have been mapped to Xq28 and Xq21-q22, respectively. SPG1 shows a mutation in the gene for neural cell adhesion molecule L1 (LICAM), which is an axonal glycoprotein involved in neuronal migration and differentiation. Different mutations of the same L1 gene also cause. MASA (mental retardation, aphasia, spastic paraplegia, adducted thumbs) syndrome and X-linked hydrocephalus. SPG2 shows mutations in one of the major myelin proteins, the proteolipid protein (PLP) gene, and is allelic to Pelizaeus-Merzbacher disease. Thus, mutations in two functionally distinct genes manifest the phenotype of X-linked spastic paraparesis. Three dominantly inherited spastic paraplegia genes have been genetically mapped to regions of chromosomes, yet no specific genes or mutations have been identified. FSP1 is mapped to a region of 7 cM on chromosome 14q12-q23 (approximately 20% of dominant FSP families) and FSP2 to 4 cM on chromosome 2p21-p24 (approximately 70% of dominant FSP families). Anticipation (increasing clinical severity in successive generations) has been observed in both FSP1 and FSP2 families. Another autosomal dominant FSP (FSP3) has been mapped in the centromeric region of chromosome 15q (< 10% of dominant FSP families). An autosomal recessive FSP has been mapped to chromosome 8q. The definite genetic heterogeneity in FSP indicates that a multitude of genes/proteins can cause spastic paraplegia. Clinical features of each of the loci which may permit differential diagnosis are discussed. We also present pedigrees of two new FSP families.
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PMID:Molecular genetics of familial spastic paraplegia: a multitude of responsible genes. 878 67

X-linked hydrocephalus (HSAS) is the most common form of inherited hydrocephalus characterized by hydrocephalus due to stenosis of the aqueduct of Sylvius, mental retardation, clasped thumbs, and spastic paraparesis. MASA syndrome (mental retardation, aphasia, shuffling gait and adducted thumbs) and SPG1 (X-linked complicated spastic paraplegia) are also X-linked disorders with overlapping clinical signs. Linkage analysis studies implicated the neural cell adhesion molecule L1 (L1CAM) gene as a candidate gene for these X-linked disorders. This genetic study analyzes the L1CAM gene in a Japanese family with members suffering from HSAS, and describes a deletion of five nucleotides in exon 8. Screening by Bg1I digestion of polymerase chain reaction (PCR) products revealed that two siblings have the same mutation and a sister was identified as a heterozygous carrier. The 5 nucleotide deletion causes a shift of the reading frame and introduces a premature stop codon 72 nucleotides downstream, which might result in a truncated protein. The mutation identified herein is a novel L1CAM mutation, which triggers hydrocephalus. We report a unique L1CAM mutation that causes HSAS: the first report of such a mutation in a Japanese family.
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PMID:A deletion of five nucleotides in the L1CAM gene in a Japanese family with X-linked hydrocephalus. 878 80

Prenatal diagnosis of non-chromosomal syndromes relies, among others, on the detection of specific morphological findings. In rare syndromes the index case may not be prenatally diagnosed but subsequent pregnancies may benefit from early diagnosis. In this article we discuss the clinical spectrum of an X-linked hereditary disease which contains hydrocephalus, congenital agenesis of the corpus callosum, adducted thumbs, shuffling gait, aphasia, mental retardation, and at times other associated findings. The purpose of this case report is to describe the prenatal sonographic findings of a fetus affected with adducted thumbs, hydrocephaly, and agenesis of te corpus callosum. The patient was referred at 22 1/2 weeks' gestation for prenatal diagnosis. Ultrasound revealed a male fetus with dilatation of the lateral ventricles and partial agenesis of the corpus callosum. The fetal hands showed the thumbs to be fixed in a flexed-adducted position. These findings were consistent with the MASA spectrum (mental retardation-aphasia-shuffling gait-adducted thumbs) present in the older brother. The patient elected to terminate the pregnancy and autopsy confirmed the sonographic findings. In conclusion, prenatal sonography, especially the presence of adducted thumbs, allowed prenatal diagnosis of the second affected child with the MASA spectrum in this family. This morphology-based approach becomes feasible between postmenstrual weeks 15 and 20. Prior to this gestational age, the diagnosis should rely on molecular biology tests.
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PMID:Transvaginal sonographic detection of adducted thumbs, hydrocephalus, and agenesis of the corpus callosum at 22 postmenstrual weeks: the masa spectrum or L1 spectrum. A case report and review of the literature. 880 96

Mutations in the gene encoding the neuronal cell adhesion molecule L1 are responsible for several syndromes with clinical overlap, including X-linked hydrocephalus (XLH, HSAS), MASA (mental retardation, aphasias, shuffling gait, adducted thumbs) syndrome, complicated X-linked spastic paraplegia (SP 1), X-linked mental retardation-clasped thumb (MR-CT) syndrome, and some forms of X-linked agenesis of the corpus callosum (ACC). We review 34 L1 mutations in patients with these phenotypes.
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PMID:The clinical spectrum of mutations in L1, a neuronal cell adhesion molecule. 882 52


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