title: Identification of a rare 17p13.3 duplication including the BHLHA9 and YWHAE genes in a family with developmental delay and behavioural problems.
abstract: BACKGROUND
  Deletions and duplications of the PAFAH1B1 and YWHAE genes in 17p13.3 are associated with different clinical phenotypes. In particular, deletion of PAFAH1B1 causes isolated lissencephaly while deletions involving both PAFAH1B1 and YWHAE cause Miller-Dieker syndrome. Isolated duplications of PAFAH1B1 have been associated with mild developmental delay and hypotonia, while isolated duplications of YWHAE have been associated with autism. In particular, different dysmorphic features associated with PAFAH1B1 or YWHAE duplication have suggested the need to classify the patient clinical features in two groups according to which gene is involved in the chromosomal duplication.
  
  
  METHODS
  We analyze the proband and his family by classical cytogenetic and array-CGH analyses. The putative rearrangement was confirmed by fluorescence in situ hybridization.
  
  
  RESULTS
  We have identified a family segregating a 17p13.3 duplication extending 329.5 kilobases by FISH and array-CGH involving the YWHAE gene, but not PAFAH1B1, affected by a mild dysmorphic phenotype with associated autism and mental retardation. We propose that BHLHA9, YWHAE, and CRK genes contribute to the phenotype of our patient. The small chromosomal duplication was inherited from his mother who was affected by a bipolar and borderline disorder and was alcohol addicted.
  
  
  CONCLUSIONS
  We report an additional familial case of small 17p13.3 chromosomal duplication including only BHLHA9, YWHAE, and CRK genes. Our observation and further cases with similar microduplications are expected to be diagnosed, and will help better characterise the clinical spectrum of phenotypes associated with 17p13.3 microduplications.
authors.forename: Valeria
authors.initials: V
authors.lastname: Capra
authors.forename: Marisol
authors.initials: M
authors.lastname: Mirabelli-Badenier
authors.forename: Michela
authors.initials: M
authors.lastname: Stagnaro
authors.forename: Andrea
authors.initials: A
authors.lastname: Rossi
authors.forename: Elisa
authors.initials: E
authors.lastname: Tassano
authors.forename: Stefania
authors.initials: S
authors.lastname: Gimelli
authors.forename: Giorgio
authors.initials: G
authors.lastname: Gimelli
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000235:genetics; D048948:14-3-3 Proteins / Q000235:genetics*; D001321:Autistic Disorder / Q000150:complications; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D002648:Child; D002886:Chromosomes, Human, Pair 17; D054221:Classical Lissencephalies and Subcortical Band Heterotopias / Q000000981:diagnostic imaging / Q000209:etiology / Q000235:genetics*; D020440:Gene Duplication; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008607:Intellectual Disability / Q000150:complications / Q000235:genetics; D059785:Karyotype; D008279:Magnetic Resonance Imaging; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D050737:Proto-Oncogene Proteins c-crk / Q000235:genetics; D011877:Radionuclide Imaging
chemical_list: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D048948:14-3-3 Proteins; D051792:Basic Helix-Loop-Helix Proteins; D008869:Microtubule-Associated Proteins; D050737:Proto-Oncogene Proteins c-crk; C571985:BHLHA9 protein, human; C485285:CRK protein, human; C482983:YWHAE protein, human; C084102:PAFAH1B1 protein, human