title: Parental imbalances involving chromosomes 15q and 22q may predispose to the formation of de novo pathogenic microdeletions and microduplications in the offspring.
abstract: Microarray-based comparative genomic hybridization (array-CGH) led to the discovery of genetic abnormalities among patients with complex phenotype and normal karyotype. Also several apparently normal individuals have been found to be carriers of cryptic imbalances, hence the importance to perform parental investigations after the identification of a deletion/duplication in a proband. Here, we report the molecular cytogenetic characterization of two individuals in which the microdeletions/duplications present in their parents could have predisposed and facilitated the formation of de novo pathogenic different copy number variations (CNVs). In family 1, a 4-year-old girl had a de novo pathogenic 10.5 Mb duplication at 15q21.2q22.2, while her mother showed a 2.262 Mb deletion at 15q13.2q13.3; in family 2, a 9-year-old boy had a de novo 1.417 Mb deletion at 22q11.21 and a second paternal deletion of 247 Kb at 22q11.23 on the same chromosome 22. Chromosome 22 at band q11.2 and chromosome 15 at band q11q13 are considered unstable regions. We could hypothesize that 15q13.2q13.3 and 22q11.21 deletions in the two respective parents might have increased the risk of rearrangements in their children. This study highlights the difficulty to make genetic counseling and predict the phenotypic consequences in these situations.
authors.affiliation: Unità Operativa di Neurochirurgia, Istituto Giannina Gaslini,Genova, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Capra
authors.forename: Samantha
authors.initials: S
authors.lastname: Mascelli
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Garrè
authors.forename: Paolo
authors.initials: P
authors.lastname: Nozza
authors.forename: Carlotta
authors.initials: C
authors.lastname: Vaccari
authors.forename: Lara
authors.initials: L
authors.lastname: Bricco
authors.forename: Frédérique
authors.initials: F
authors.lastname: Sloan-Béna
authors.forename: Stefania
authors.initials: S
authors.lastname: Gimelli
authors.forename: Cristina
authors.initials: C
authors.lastname: Cuoco
authors.forename: Giorgio
authors.initials: G
authors.lastname: Gimelli
authors.forename: Elisa
authors.initials: E
authors.lastname: Tassano
mesh_terms: D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D055028:Comparative Genomic Hybridization; D005190:Family; D005260:Female; D020440:Gene Duplication / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007231:Infant, Newborn; D040582:Inheritance Patterns / Q000235:genetics; D008297:Male; D010290:Parents; D010375:Pedigree; D011247:Pregnancy