Document Detail

Molecular analysis of mutations in the gene FMR-1 segregating in fragile X families.
MedLine Citation:
PMID:  7902319     Owner:  NLM     Status:  MEDLINE    
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.
P Steinbach; D Wöhrle; G Tariverdian; I Kennerknecht; G Barbi; H Edlinger; H Enders; M Götz-Sothmann; H Heilbronner; D Hosenfeld
Related Documents :
24565469 - Early-onset dementias: diagnostic and etiological considerations.
16449639 - Developmental profile of h19 differentially methylated domain (dmd) deletion alleles re...
3338799 - Population cytogenetics of rare fragile sites in japan.
15234339 - Searching for genomic variants in igf2 and cdkn1c in silver-russell syndrome patients.
23948919 - Juvenile frontotemporal dementia with parkinsonism associated with tau mutation g389r.
11464249 - No mutations in the coding region of the rett syndrome gene mecp2 in 59 autistic patients.
23875689 - Colorectal cancer-susceptibility single nucleotide polymorphisms in korean population.
16687409 - Identification of a specific domain required for dimerization of activation-induced cyt...
25273069 - Shroom3 contributes to the maintenance of the glomerular filtration barrier integrity.
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    
Abteilung Klinische Genetik, Universität Ulm, Germany.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Alternative Splicing
DNA / metabolism
DNA Mutational Analysis
Embryonic and Fetal Development
Fragile X Mental Retardation Protein
Fragile X Syndrome / genetics*
Gene Conversion
Gene Expression Regulation
Genes, Recessive
Mutation / genetics*
Nerve Tissue Proteins / genetics
Polymorphism, Restriction Fragment Length
RNA-Binding Proteins*
Repetitive Sequences, Nucleic Acid*
Restriction Mapping
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

Previous Document:  Parental origin of triploidy in human fetuses: evidence for genomic imprinting.
Next Document:  Complete genomic sequence of the human retinoblastoma susceptibility gene.