Abstract
BackgroundDeletions 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.MethodsWe analyze the proband and his family by classical cytogenetic and array-CGH analyses. The putative rearrangement was confirmed by fluorescence in situ hybridization.ResultsWe 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.ConclusionsWe 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.
Highlights
Deletions and duplications of the PAFAH1B1 and YWHAE genes in 17p13.3 are associated with different clinical phenotypes
Bruno et al [5] proposed to divide 17p13.3 microduplications in two different classes: class I microduplications involving YWHAE but not PAFAH1B1 showing a phenotype characterized by learning difficulties and/or autism with or without other congenital abnormalities; class II microduplications always harboring PAFAH1B1 that may include the genomic region encompassing the CRK and YWHAE genes, which are associated with developmental delay, psychomotor delay, and associated hypotonia
We report on a 7-year-old boy and his mother presenting a novel class I 17p13.3 microduplication measuring about 329.5 Kb in length and involving only seven genes, including YWHAE, CRK, and BHLHA9
Summary
Deletions and duplications of the PAFAH1B1 and YWHAE genes in 17p13.3 are associated with different clinical phenotypes. Isolated duplications of PAFAH1B1 have been associated with mild developmental delay and hypotonia, while isolated duplications of YWHAE have been associated with autism. 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. Bruno et al [5] proposed to divide 17p13.3 microduplications in two different classes: class I microduplications involving YWHAE but not PAFAH1B1 showing a phenotype characterized by learning difficulties and/or autism with or without other congenital abnormalities; class II microduplications always harboring PAFAH1B1 that may include the genomic region encompassing the CRK and YWHAE genes, which are associated with developmental delay, psychomotor delay, and associated hypotonia.
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