Unexpected identification of two interstitial deletions in a patient with a pericentric inversion of a chromosome 4 and an abnormal phenotype.
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.
Piovani
Giovanna
G
Biology and Genetics Division, Department of Biomedical Sciences and Biotechnology, University of Brescia, Viale Europa 11, 25123 Brescia, Italy.
Borsani
Giuseppe
G
Bertini
Valeria
V
Kalscheuer
Vera M
VM
Viertel
Petra
P
Bellotti
Daniela
D
Valseriati
Daniela
D
Barlati
Sergio
S
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