title: Cytogenetic, FISH and array-CGH characterization of a complex chromosomal rearrangement carried by a mentally and language impaired patient.
abstract: We describe a patient with an abnormal phenotype and a de novo CCR consisting of a reciprocal translocation between chromosomes 1 and 15 and an insertion of an interstitial segment from chromosome 2 within chromosome 1. The CCR was studied by QFQ banding and FISH. The apparently balanced rearrangement was further investigated with array-CGH, that uncovered three cryptic deletions on chromosome 2q. By means of BAC-FISH two deletions were located at the breakpoints of the insertion, at 2q14.3 and 2q31.2, and one at 2q22.2, in the region of 2q translocated on derivative 1. Consequently, in silico analysis of the deleted regions was performed. Among deleted genes, particularly interesting seems to be CNTNAP5, encoding a member of the neurexin superfamily. The three mouse orthologues are highly expressed in adult brain tissues. We speculate that loss of CNTNAP5 might contribute to the developmental language delay of this patient, similar to CNTNAP2, another member of the same protein family, whose alterations have been recently associated with delay in the age at first word in autistic patients. At clinical patient's evaluation, a Mowat-Wilson syndrome (MWS) like appearance was noted. The disease is caused by mutation or deletion of ZEB2 gene, located in our patient 794Kb distally to the 2q22.2 deletion, in the chromosome 2 segment inserted into the derivative 1. The loss of the gene has been excluded by the array-CGH results, but its proximity to the deleted segment and/or its insertion in a different genetic context might influence and consequently impair its expression. Our study confirms that array-CGH is a precious method to identify cryptic imbalances in CCR carriers and underlie the essential role of BAC-FISH as second step of analysis to assess the reciprocal position of the chromosomal segments involved in CCRs and the exact mapping of the imbalances.
authors.affiliation: Lab. Citogenetica Medica e Genetica Molecolare, IRCCS, Istituto Auxologico Italiano, Milan, Italy. l.ballarati@auxologico.it
authors.forename: Lucia
authors.initials: L
authors.lastname: Ballarati
authors.forename: Maria Paola
authors.initials: MP
authors.lastname: Recalcati
authors.forename: Maria Francesca
authors.initials: MF
authors.lastname: Bedeschi
authors.forename: Faustina
authors.initials: F
authors.lastname: Lalatta
authors.forename: Chiara
authors.initials: C
authors.lastname: Valtorta
authors.forename: Melissa
authors.initials: M
authors.lastname: Bellini
authors.forename: Palma
authors.initials: P
authors.lastname: Finelli
authors.forename: Lidia
authors.initials: L
authors.lastname: Larizza
authors.forename: Daniela
authors.initials: D
authors.lastname: Giardino
mesh_terms: D000328:Adult; D001483:Base Sequence; D002869:Chromosome Aberrations; D019457:Chromosome Breakage; D020223:Chromosome Painting; D002878:Chromosomes, Human, Pair 1; D002884:Chromosomes, Human, Pair 15; D002889:Chromosomes, Human, Pair 2; D055028:Comparative Genomic Hybridization; D020732:Cytogenetic Analysis; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008607:Intellectual Disability / Q000235:genetics*; D007806:Language Disorders / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D017384:Sequence Deletion; D014178:Translocation, Genetic
chemical_list: D004247:DNA