A 7 Mb duplication at 22q13 in a girl with bipolar disorder and hippocampal malformation

Tiziano Pramparo, Manuela De Gregori, Stefania Gimelli, Roberto Ciccone, Domenico Frondizi, Thomas Liehr, Simona Pellacani, Gabriele Masi, Paola Brovedani, Orsetta Zuffardi, Renzo Guerrini

Research output: Contribution to journalArticlepeer-review


We identified a duplication of 22q13.1-q13.2 in a 10-year-old girl and demonstrated that this duplication was the recombinant product of a maternal intrachromosomal insertion. Phenotypic characteristics included prominent forehead, small low-set ears, hypertelorism, epicanthal folds, small palpebral fissures, short philtrum, and syndactyly. MRI of the brain revealed high signal abnormalities in the periventricular white matter, a hypoplastic corpus callosum, under-rotated hippocampus on the left and atrophic hippocampus on the right. Since age 5, the child's behavior has shown cyclic maniacal episodes with severely disorganized mood and behavior. Psychiatric and cognitive assessment led to a diagnosis of bipolar disorder not otherwise specified, manic episodes, attention deficit hyperactivity disorder and moderate mental retardation. Array-CGH revealed an interstitial duplication of 6.9 Mb at chromosome 22q: dup(22)(q13.1q13-2). FISH using BAC clones confirmed the array-CGH results and demonstrated that the duplication was inverted. G-banding analysis in the proposita's mother revealed a banding pattern suggestive of an intrachromosomal insertion, as demonstrated by dual-color FISH with BACs that were duplicated in the proposita and multicolor-banding (MCB) based on microdissection derived region-specific libraries for chromosome 22. Our findings suggest that in both seemingly de novo deletions and duplications, the parent transmitting the imbalance should be investigated for possible balanced rearrangements. This report reinforces previous evidence that chromosome imbalances, and thus gene dosage effects, may be at the basis of some psychiatric disorders. Stringent correlations between submicroscopic imbalances, specific behavioral phenotypes and brain imaging will possibly help in dissecting complex behavioral traits.

Original languageEnglish
Pages (from-to)1754-1760
Number of pages7
JournalAmerican Journal of Medical Genetics, Part A
Issue number13
Publication statusPublished - Jul 1 2008


  • 22q13.1-q13-2 duplication
  • Array-CGH
  • Bipolar disorder
  • Cognitive impairment
  • Hippocampal malformation
  • Intrachromosomal insertions

ASJC Scopus subject areas

  • Genetics(clinical)


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