title: Micro-array analyses decipher exceptional complex familial chromosomal rearrangement.
abstract: Recently there has been an increased interest in large-scale genomic variation and clinically in the consequences of haploinsufficiency of genomic segments or disruption of normal gene function by chromosome rearrangements. Here, we present an extraordinary case in which both mother and daughter presented with unexpected chromosomal rearrangement complexity, which we characterized with array-CGH, array painting and multicolor large insert clone hybridizations. We found the same 12 breakpoints involving four chromosomes in both mother and daughter. In addition, the daughter inherited a microdeletion from her father. We mapped all breakpoints to the resolution level of breakpoint spanning clones. Genes were found within 7 of the 12 breakpoint regions, some of which were disrupted by the chromosome rearrangement. One of the rearrangements disrupted a locus, which has been discussed as a quantitative trait locus for fetal hemoglobin expression in adults. Interestingly, both mother and daughter show persistent fetal hemoglobin levels. We detail the most complicated familial complex chromosomal rearrangement reported to date and thus an extreme example of inheritance of chromosomal rearrangements without error in meiotic segregation.
authors.affiliation: Institut für Humangenetik, Technische Universität München, Trogerstr. 32, 81675 München, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Fauth
authors.forename: Susan M
authors.initials: SM
authors.lastname: Gribble
authors.forename: Keith M
authors.initials: KM
authors.lastname: Porter
authors.forename: Montserrat
authors.initials: M
authors.lastname: Codina-Pascual
authors.forename: Bee Ling
authors.initials: BL
authors.lastname: Ng
authors.forename: Jürgen
authors.initials: J
authors.lastname: Kraus
authors.forename: Sabine
authors.initials: S
authors.lastname: Uhrig
authors.forename: Jürgen
authors.initials: J
authors.lastname: Leifheit
authors.forename: Thomas
authors.initials: T
authors.lastname: Haaf
authors.forename: Heike
authors.initials: H
authors.lastname: Fiegler
authors.forename: Nigel P
authors.initials: NP
authors.lastname: Carter
authors.forename: Michael R
authors.initials: MR
authors.lastname: Speicher
mesh_terms: D002648:Child; D002871:Chromosome Banding; D019457:Chromosome Breakage; D025063:Chromosome Disorders / Q000235:genetics / Q000473:pathology; D002880:Chromosomes, Human, Pair 11; D002890:Chromosomes, Human, Pair 20; D002896:Chromosomes, Human, Pair 6; D002899:Chromosomes, Human, Pair 9; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D007621:Karyotyping; D046228:Microarray Analysis / Q000379:methods; D008957:Models, Genetic; D009693:Nucleic Acid Hybridization / Q000379:methods; D014178:Translocation, Genetic / Q000235:genetics*