title: Concurrent transposition of distal 6p and 20q to the 22q telomere: a recurrent benign chromosomal variant.
abstract: We report the second instance of a complex unbalanced rearrangement consisting of distal trisomy 6p and 20q due to the concurrent transposition of distal 6p and 20q to the 22q telomere, previously described as a benign familial chromosomal variant. In the previous case, the nonpathogenicity of the rearrangement was based on the absence of genotypic differences between the affected proband and his normal father, and on the absence of imprinted genes in the unbalanced region. We now describe the same variant in an unrelated affected subject, in whom testing confirmed the diagnosis of Angelman syndrome, and in his healthy father. Molecular investigations confirmed that the two families have an identical subtelomeric rearrangement. However, genotyping of the flanking sequences on 22q showed a completely different pattern in the two families, demonstrating that they are indeed unrelated. Array-CGH analysis with a resolution of approximately 20 kb (Kit 244A, Agilent) defined a deletion size of 5.9 Mb on 15q11.2. No other imbalances were visible at subtelomeric regions. Further Array-CGH analysis using DNA of the proband (as test) and his mother (as reference) did not detect any duplication at the 6p and 20q subtelomeric regions. The proband and his father appear to have a copy number of the transposed regions equal to that of individuals with a normal repartition of the subtelomeric regions. This is not suggestive of a trisomy but rather of CNV regions. This type of rearrangement could define a new class of polymorphic variants, i.e. positional variants, as observed for pericentromeric heterochromatin.
authors.affiliation: IRCCS Eugenio Medea, Via Don Luigi Monza 20, 23842 Bosisio Parini, Lecco, Italy. clara.bonaglia@bp.lnf.it <clara.bonaglia@bp.lnf.it>
authors.forename: Maria Clara
authors.initials: MC
authors.lastname: Bonaglia
authors.forename: Roberto
authors.initials: R
authors.lastname: Giorda
authors.forename: Silvana
authors.initials: S
authors.lastname: Beri
authors.forename: Gregory B
authors.initials: GB
authors.lastname: Peters
authors.forename: Edwin P
authors.initials: EP
authors.lastname: Kirk
authors.forename: Dorothy
authors.initials: D
authors.lastname: Hung
authors.forename: Roberto
authors.initials: R
authors.lastname: Ciccone
authors.forename: Giulietta
authors.initials: G
authors.lastname: Gottardi
authors.forename: Orsetta
authors.initials: O
authors.lastname: Zuffardi
mesh_terms: D017204:Angelman Syndrome / Q000175:diagnosis / Q000235:genetics*; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics*; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D014644:Genetic Variation; D006801:Humans; D007223:Infant; D008297:Male; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D011110:Polymorphism, Genetic; D016615:Telomere / Q000235:genetics*