Document Detail


Molecular analysis of mutations in the gene FMR-1 segregating in fragile X families.
MedLine Citation:
PMID:  7902319     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Molecular genetic analysis of the transmission of mutations in 73 families with fragile X (one of the largest samples evaluated so far) has confirmed previous hypotheses that the fragile X syndrome results from two consecutive mutational steps, designated "premutation" and "full fragile X mutation". These mutations give rise to expansions of restriction fragments, most probably by amplification of the FMR-1 CGG repeat. Premutations are identified by small expansions that apparently have no effect on either the clinical or the cellular phenotype. Full mutations are reflected by large expansions and hypermethylation of the expanded gene region. All males showing large expansions were affected. Individuals with full mutations also expressed the fragile X, with only one exception. An affected "mosaic" male, showing a predominance of premutated fragments in his leukocytes, was shown to be fragile-X-negative on different occasions. About 50% of heterozygotes with full mutations were reported by clinicians to be mentally retarded. Conversion of the premutation to the full mutation may occur at oogenesis, as previously suggested, or after formation of a zygote at an early transitional stage in development when the CGG repeat behaves as a mitotically unstable element on maternally derived/imprinted X chromosomes carrying a premutation of sufficient repeat length.
Authors:
P Steinbach; D Wöhrle; G Tariverdian; I Kennerknecht; G Barbi; H Edlinger; H Enders; M Götz-Sothmann; H Heilbronner; D Hosenfeld
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Human genetics     Volume:  92     ISSN:  0340-6717     ISO Abbreviation:  Hum. Genet.     Publication Date:  1993 Nov 
Date Detail:
Created Date:  1994-01-05     Completed Date:  1994-01-05     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7613873     Medline TA:  Hum Genet     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  491-8     Citation Subset:  IM    
Affiliation:
Abteilung Klinische Genetik, Universität Ulm, Germany.
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MeSH Terms
Descriptor/Qualifier:
Alternative Splicing
DNA / metabolism
DNA Mutational Analysis
Embryonic and Fetal Development
Female
Fragile X Mental Retardation Protein
Fragile X Syndrome / genetics*
Gene Conversion
Gene Expression Regulation
Genes, Recessive
Heterozygote
Humans
Male
Methylation
Mosaicism
Mothers
Mutagenesis
Mutation / genetics*
Nerve Tissue Proteins / genetics
Pedigree
Phenotype
Polymorphism, Restriction Fragment Length
RNA-Binding Proteins*
Repetitive Sequences, Nucleic Acid*
Restriction Mapping
Zygote
Chemical
Reg. No./Substance:
0/FMR1 protein, human; 0/Nerve Tissue Proteins; 0/RNA-Binding Proteins; 139135-51-6/Fragile X Mental Retardation Protein; 9007-49-2/DNA

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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