title: Constitutional chromosomal events at 22q11 and 15q26 in a child with a pilocytic astrocytoma of the spinal cord.
abstract: We report on a 9-years-old patient with mild intellectual disability, facial dimorphisms, bilateral semicircular canal dysplasia, periventricular nodular heterotopias, bilateral hippocampal malrotation and abnormal cerebellar foliation, who developed mild motor impairment and gait disorder due to a pilocytic astrocytoma of the spinal cord. Array-CGH analysis revealed two paternal inherited chromosomal events: a 484.3 Kb duplication on chromosome 15q26.3 and a 247 Kb deletion on 22q11.23. Further, a second de novo 1.5 Mb deletion on 22q11.21 occurred. Chromosome 22 at q11.2 and chromosome 15 at q24q26 are considered unstable regions subjected to copy number variations, i.e. structural alterations of genome, mediated by low copy repeat sequences or segmental duplications. The link between some structural CNVs, which compromise fundamental processes controlling DNA stability, and genomic disorders suggest a plausible scenario for cancer predisposition. Evaluation of the genes at the breakpoints cannot account simultaneously for the phenotype and tumour development in this patient. The two paternal inherited CNVs arguably are not pathogenic and do not contribute to the clinical manifestations. Similarly, although the de novo large deletion at 22q11.21 overlaps with the Di George (DGS) critical region and results in haploinsufficiency of genes compromising critical processes for DNA stability, this case lacks several hallmarks of DGS.
authors.affiliation: Istituto Giannina Gaslini, via G. Gaslini 5, 16147 Genoa, Italy.
authors.forename: Samantha
authors.initials: S
authors.lastname: Mascelli
authors.affiliation: Istituto Giannina Gaslini, via G. Gaslini 5, 16147 Genoa, Italy.
authors.forename: Mariasavina
authors.initials: M
authors.lastname: Severino
authors.affiliation: Istituto Giannina Gaslini, via G. Gaslini 5, 16147 Genoa, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Raso
authors.affiliation: Istituto Giannina Gaslini, via G. Gaslini 5, 16147 Genoa, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Nozza
authors.affiliation: Istituto Giannina Gaslini, via G. Gaslini 5, 16147 Genoa, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Tassano
authors.affiliation: Istituto Giannina Gaslini, via G. Gaslini 5, 16147 Genoa, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Morana
authors.affiliation: Istituto Giannina Gaslini, via G. Gaslini 5, 16147 Genoa, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: De Marco
authors.affiliation: Istituto Giannina Gaslini, via G. Gaslini 5, 16147 Genoa, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Merello
authors.affiliation: Istituto Giannina Gaslini, via G. Gaslini 5, 16147 Genoa, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Milanaccio
authors.affiliation: Istituto Giannina Gaslini, via G. Gaslini 5, 16147 Genoa, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Pavanello
authors.affiliation: Istituto Giannina Gaslini, via G. Gaslini 5, 16147 Genoa, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Rossi
authors.affiliation: Istituto Giannina Gaslini, via G. Gaslini 5, 16147 Genoa, Italy.
authors.forename: Armando
authors.initials: A
authors.lastname: Cama
authors.affiliation: Istituto Giannina Gaslini, via G. Gaslini 5, 16147 Genoa, Italy.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Garrè
authors.affiliation: Istituto Giannina Gaslini, via G. Gaslini 5, 16147 Genoa, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Capra
keywords: 15q duplication; 22q11.2 deletion; Pilocytic astrocytoma; Semicircular canal dysplasia; Spinal cord