title: Mapping genomic deletions down to the base: a quantitative copy number scanning approach used to characterise and clone the breakpoints of a recurrent 7p14.2p15.3 deletion.
abstract: With the recent advances in genomic research, it has become apparent that a substantial part of human malformation and mental retardation is caused by imbalances in genomic content. Thus, there is an increasing need for versatile methods allowing a detailed mapping and cloning of the actual rearrangements. We have combined the flexibility of real-time quantitative PCR with the knowledge of human genome sequence to perform a copy number scanning in three patients known to harbour a deletion in the 7p14p15 locus. In two of the patients the actual breakpoints were cloned and sequenced, whereas the breakpoint of the third patient was mapped to a region previously predicted to be prone for rearrangements. One patient also harboured an inversion in connection with the deletion that disrupted the HDAC9 gene. All three patients showed clinical characteristics reminiscent of the hand-foot-genital syndrome and were deleted for the entire HOXA cluster. Two patients were also deleted for DFNA5, a gene implicated in dominant nonsyndromic hearing impairment, but neither patient showed signs of reduced hearing capabilities. The described copy number scanning approach is largely independent of the genomic locus and may be a valuable tool for characterising a large spectrum of deletions.
authors.affiliation: Department of Clinical Genetics, University Hospital Copenhagen, 4062, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark. mdunoe@rh.dk
authors.forename: Morten
authors.initials: M
authors.lastname: Dunø
authors.forename: Hanne
authors.initials: H
authors.lastname: Hove
authors.forename: Maria
authors.initials: M
authors.lastname: Kirchhoff
authors.forename: Koenraad
authors.initials: K
authors.lastname: Devriendt
authors.forename: Marianne
authors.initials: M
authors.lastname: Schwartz
mesh_terms: D002675:Child, Preschool; D002897:Chromosomes, Human, Pair 7; D003001:Cloning, Molecular; D003582:Cytogenetics; D004247:DNA / Q000235:genetics; D019066:Facies; D005260:Female; D017353:Gene Deletion; D015894:Genome, Human; D006655:Histone Deacetylases / Q000235:genetics; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics; D007621:Karyotyping; D008297:Male; D018895:Microsatellite Repeats; D008957:Models, Genetic; D005810:Multigene Family; D009693:Nucleic Acid Hybridization; D016133:Polymerase Chain Reaction; D011960:Receptors, Estrogen / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D017422:Sequence Analysis, DNA; D013577:Syndrome; D000094524:Gasdermins
chemical_list: D004247:DNA; D006655:Histone Deacetylases; D011960:Receptors, Estrogen; D012097:Repressor Proteins; C111432:GSDME protein, human; D000094524:Gasdermins; C486544:HDAC9 protein, human