Document Detail


Evidence for subtelomeric exchange of 3.3 kb tandemly repeated units between chromosomes 4q35 and 10q26: implications for genetic counselling and etiology of FSHD1.
MedLine Citation:
PMID:  8968754     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant myopathy, clinically characterized by asymmetric weakness of muscles in the face, shoulder girdle and upper arm. Deletion of an integral number of 3.3 kb repeated units within a highly polymorphic EcoRI fragment at chromosome 4q35, generating a relatively short EcoRI fragment (< 35 kb), has been shown to cause FSHD1. Probe p13E-11 detects these short fragments in FSHD1 patients, and has therefore been used for diagnostic DNA analysis. However, the reliability of this analysis has been hampered by cross-hybridization of p13E-11 to chromosome 10q26-linked EcoRI fragments of comparable size, which also contain a variable number of 3.3 kb repeated units. Recently, a BinI restriction site was identified within each of the repeated units derived from chromosome 10q26, which enables differentiation of the two polymorphic p13E-11 loci in most cases without haplotype analysis. Remarkably, applying the differential analysis to screen DNA of 160 Dutch cases referred to us for FSHD1 diagnosis, we obtained evidence for subtelomeric exchange of 3.3 kb repeated units between chromosomes 4q35 and 10q26 in affected and unaffected individuals. Subsequently, analysis of 50 unrelated control samples indicated such exchange between chromosomes 4q35 and 10q26 in at least 20% of the population. These subtelomeric rearrangements have generated a novel interchromosomal polymorphism, which has implications for the specificity and sensitivity of the differential restriction analysis for diagnostic purposes. Moreover, the high frequency of the interchromosomal exchanges of 3.3 kb repeated units suggests that they probably do not contain (part of) the FSHD1 gene, and supports position effect variegation as the most likely mechanism for FSHD1.
Authors:
J C van Deutekom; E Bakker; R J Lemmers; M J van der Wielen; E Bik; M H Hofker; G W Padberg; R R Frants
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Human molecular genetics     Volume:  5     ISSN:  0964-6906     ISO Abbreviation:  Hum. Mol. Genet.     Publication Date:  1996 Dec 
Date Detail:
Created Date:  1997-03-14     Completed Date:  1997-03-14     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9208958     Medline TA:  Hum Mol Genet     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  1997-2003     Citation Subset:  IM    
Affiliation:
MGC-Department of Human Genetics, Sylvius Laboratory, Leiden University, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
Chromosomes, Human, Pair 10*
Chromosomes, Human, Pair 4*
Female
Gene Rearrangement*
Humans
Male
Muscular Dystrophies / genetics*
Nuclear Proteins
Pedigree
Proteins / genetics*
Repetitive Sequences, Nucleic Acid / genetics*
Telomere / genetics
Chemical
Reg. No./Substance:
0/FRG1 protein, human; 0/Nuclear Proteins; 0/Proteins

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