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Identification of a rare 17p13.3 duplication including the BHLHA9 and YWHAE genes in a family with developmental delay and behavioural problems

Valeria Capra1, Marisol Mirabelli-Badenier2, Michela Stagnaro2, Andrea Rossi3, Elisa Tassano5, Stefania Gimelli4 and Giorgio Gimelli5*

Author Affiliations

1 U.O. Neurochirurgia, Istituto G.Gaslini, Genova, Italy

2 U.O. Neuropsichiatria, Istituto G.Gaslini, Genova, Italy

3 Dipartimento di Neuroradiologia, Istituto G. Gaslini, Genova, Italy

4 Service of Genetic Medicine, University Hospitals of Geneva, Geneva, Switzerland

5 Laboratorio di Citogenetica, Istituto G. Gaslini, Genova, Italy

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BMC Medical Genetics 2012, 13:93  doi:10.1186/1471-2350-13-93

Published: 4 October 2012



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.


We analyze the proband and his family by classical cytogenetic and array-CGH analyses. The putative rearrangement was confirmed by fluorescence in situ hybridization.


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.


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.

Familial 17p13.3 duplication syndrome; PAFAH1B1 and YWHAE genes; Array-CGH