title: FSHD associated DNA rearrangements are due to deletions of integral copies of a 3.2 kb tandemly repeated unit.
abstract: Facioscapulohumeral muscular dystrophy (FSHD) is a neuromuscular disorder characterized by progressive weakness of the facial, shoulder and upper arm muscles. The disease is associated with DNA rearrangements which are detectable using probe p13E-11 (D4F104S1) in DNA digested with EcoRI or other restriction enzymes. We have cloned and characterized the rearranged EcoRI fragment of four unrelated FSHD patients. Restriction fragment mapping and DNA sequence analysis showed that the proximal and distal parts of the EcoRI fragment, which flank a region of tandemly repeated 3.2 kb units, are identical in normal and rearranged EcoRI fragments. These results strongly support the hypothesis that the FSHD associated rearrangements are due to deletions of integral copies of the 3.2 kb repeated unit. Since these repeated units are likely to form part of the FSHD transcription unit, the variation in repeat unit number might affect the function of the gene product. Hence, our data confine the FSHD gene region and thus provide a starting point for cloning the FSHD gene.
authors.affiliation: MGC-Department of Human Genetics, Leiden University, The Netherlands.
authors.forename: J C
authors.initials: JC
authors.lastname: van Deutekom
authors.forename: C
authors.initials: C
authors.lastname: Wijmenga
authors.forename: E A
authors.initials: EA
authors.lastname: van Tienhoven
authors.forename: A M
authors.initials: AM
authors.lastname: Gruter
authors.forename: J E
authors.initials: JE
authors.lastname: Hewitt
authors.forename: G W
authors.initials: GW
authors.lastname: Padberg
authors.forename: G J
authors.initials: GJ
authors.lastname: van Ommen
authors.forename: M H
authors.initials: MH
authors.lastname: Hofker
authors.forename: R R
authors.initials: RR
authors.lastname: Frants
mesh_terms: D001132:Arm; D001483:Base Sequence; D002874:Chromosome Mapping; D002894:Chromosomes, Human, Pair 4; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics*; D015246:Deoxyribonuclease EcoRI; D005152:Facial Muscles / Q000503:physiopathology; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009136:Muscular Dystrophies / Q000235:genetics*; D009838:Oligodeoxyribonucleotides; D010375:Pedigree; D011110:Polymorphism, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D015183:Restriction Mapping; D017384:Sequence Deletion; D012782:Shoulder
chemical_list: D009838:Oligodeoxyribonucleotides; D004247:DNA; D015246:Deoxyribonuclease EcoRI