title: Unexpected identification of two interstitial deletions in a patient with a pericentric inversion of a chromosome 4 and an abnormal phenotype.
abstract: Interstitial deletions and pericentric inversions of chromosome 4 appear to be unusual phenomena. Here, we report the case of a 14-year-old boy with severe psychomotor retardation with a de novo 46,XY,der(4)del(p15.2p15.31)inv(4)(p15.2q13.3)del(4)(q13.2q13.2) karyotype. We used FISH analysis with YAC and BAC clones to characterise the inversion's breakpoints. A complex event with six breakpoints was found, characterised by a pericentric inversion and two deletions, the first on the short arm of chromosome 4 (4p) and the second on the long arm of chromosome 4 (4q). The deletion events had removed two segments, one of approximately 5 Mb, from 4p, outside the inversion, and the other 2 Mb from 4q, inside the inversion. These rearrangements were not found in the parents. Microsatellite marker analysis showed that the inversion carrying chromosome 4 was derived from the father. Bioinformatic analysis of the human genome sequence allowed us to identify several hemizygotic genes in the patient, which might be involved in the pathogenesis of this clinical phenotype.
authors.affiliation: Biology and Genetics Division, Department of Biomedical Sciences and Biotechnology, University of Brescia, Viale Europa 11, 25123 Brescia, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Piovani
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Borsani
authors.forename: Valeria
authors.initials: V
authors.lastname: Bertini
authors.forename: Vera M
authors.initials: VM
authors.lastname: Kalscheuer
authors.forename: Petra
authors.initials: P
authors.lastname: Viertel
authors.forename: Daniela
authors.initials: D
authors.lastname: Bellotti
authors.forename: Daniela
authors.initials: D
authors.lastname: Valseriati
authors.forename: Sergio
authors.initials: S
authors.lastname: Barlati
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics / Q000503:physiopathology; D000293:Adolescent; D002871:Chromosome Banding; D002872:Chromosome Deletion; D007446:Chromosome Inversion; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics*; D019295:Computational Biology; D019465:Craniofacial Abnormalities / Q000235:genetics; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008607:Intellectual Disability / Q000235:genetics; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D010641:Phenotype; D011596:Psychomotor Disorders / Q000235:genetics