Document Detail

Analysis of the CMT1A-REP repeat: mapping crossover breakpoints in CMT1A and HNPP.
MedLine Citation:
PMID:  8634706     Owner:  NLM     Status:  MEDLINE    
The CMT1A-REP repeat sequence flanks a 1.5 megabase pair (Mb) segment of chromosome 17p11.2-12 which is duplicated in Charcot-Marie-Tooth neuropathy type 1A (CMT1A) and deleted in hereditary neuropathy with liability to pressure palsies (HNPP). The CMT1A-REP repeat is proposed to mediate misalignment and unequal crossover resulting in reciprocal chromosomal rearrangements in CMT1A and HNPP. We have constructed a physical map of the proximal and distal CMT1A-REP repeats. Cloned fragments from CMT1A-REP repeat regions are used to determine the size of the repeats and assess regions of homology. The crossover breakpoints were mapped in series of 30 unrelated CMT1A patients and 22 unrelated HNPP patients. The CMT1A-REP repeat spans approximately 27 kilobase pairs and appears to be continuous. Locations of restriction enzyme sites are highly conserved for the proximal and distal CMT1A-REP repeats. All crossovers mapped within the CMT1A-REP repeat sequence and heterogeneity for breakpoint location demonstrated. Seventy-seven percent (40 to 52) of CMT1A and HNPP chromosomes contained breakpoints which mapped within a 7.9 kb interval, suggesting the presence of a possible 'hotspot'for recombination in CMT1A-REP. DNA sequence analysis for 4 kb of the interval containing the majority of crossovers revealed over 98% sequence identity between proximal and distal CMT1A-REP repeat sequences. Probes useful for molecular-based diagnosis of CMT1A and HNPP are described.
H Kiyosawa; M W Lensch; P F Chance
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Human molecular genetics     Volume:  4     ISSN:  0964-6906     ISO Abbreviation:  Hum. Mol. Genet.     Publication Date:  1995 Dec 
Date Detail:
Created Date:  1996-07-08     Completed Date:  1996-07-08     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9208958     Medline TA:  Hum Mol Genet     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  2327-34     Citation Subset:  IM    
Division of Neurology, The Children's Hospital of Phildelphia, Pennsylvania 19104, USA.
Data Bank Information
Bank Name/Acc. No.:
GENBANK/L44118;  L44119;  L44120;  L44121
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MeSH Terms
Charcot-Marie-Tooth Disease / genetics*
Chromosome Mapping
Crossing Over, Genetic*
DNA / analysis
Demyelinating Diseases / genetics*
Hereditary Sensory and Motor Neuropathy / genetics*
Molecular Sequence Data
Repetitive Sequences, Nucleic Acid*
Restriction Mapping
Sequence Homology, Nucleic Acid
Grant Support
Reg. No./Substance:

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