Datensatz

Zusammenfassung

Interstitial deletions of chromosome band 4q32 are rare. We report on a 22-year-old female patient with a de novo interstitial deletion of chromosome 4q32 and a balanced translocation t(2;5)(p21;q12.1). Clinical problems of the patient comprised mild to moderate mental retardation, psychosis, obesity, broad nasal root, sparse lateral eyebrows, thin upper lip, short philtrum, micrognathia, and strabismus. Analysis by whole genome array CGH using an Agilent 244K oligonucleotide array and subsequent FISH using BAC clones from the 4q32 region revealed an unexpectedly complex rearrangement comprising a deletion of approximately 10 Mb in 4q32.1q32.3 and the insertion of two small fragments of 0.8 and 0.11 Mb originating from the derivative chromosome 4q32 into derivative chromosome 5q. The breakpoints of the t(2;5) translocation were mapped by BAC-FISH; no genes were disrupted by these breakpoints. The deleted interval in 4q32 harbored more than 30 genes, and haploinsufficiency of one or several of these genes is likely to have caused the clinical problems of the patient. Candidate genes for cognitive defects are GRIA2, GLRB, NPY1R, and NPY5R. In conclusion, this patient increases our knowledge about the phenotypic consequences of interstitial 4q32 deletions. Reports of patients with overlapping deletions will be needed to elucidate the role of individual genes and to establish genotype–phenotype correlations