Integrated analysis of clinical signs and literature data for the diagnosis and therapy of a previously undescribed 6p21.3 deletion syndrome.

Marcella Zollino (1) , Fiorella Gurrieri (1) , Daniela Orteschi (1) , Giuseppe Marangi (1) , Vincenzo Leuzzi (1) , Giovanni Neri (1)

1 Istituto di Genetica Medica

A de novo 0.3 Mb deletion on 6p21.3 was detected by array-CGH in a girl with mental retardation, drug-resistant seizures, facial dysmorphisms, gut malrotation and abnormal pancreas segmentation. Consistent with phenotypic manifestations is haploinsufficiency of SYNGAP1, that was recently demonstrated to cause nonsyndromic mental retardation, and of the flanking genes CuTA, a likely modulator of the processing and trafficking of secretory proteins in the human brain, and hPHF1, involved in HOX gene silencing. Mutations of both CuTA and hPHF1 were never reported as causative of human diseases. Likewise, the present syndromic condition was not previously described and it can be regarded as a human model confirming the suggested biological properties of the genes included in the deletion interval. In addition, experimental evidence that SYNGAP1 and CuTA are involved in the secretory pathway in neurons, through glutamate and acetylcholinesterase signalling, prompted us to consider modulation of the glutamate pathway as target of a therapeutic strategy for the seizure control.

Mots clés: array-CGH; SYNGAP1; mental retardation

Marcella Zollino, Fiorella Gurrieri, Daniela Orteschi, Giuseppe Marangi, Vincenzo Leuzzi, et al.. Integrated analysis of clinical signs and literature data for the diagnosis and therapy of a previously undescribed 6p21.3 deletion syndrome.. European Journal of Human Genetics, 2010, ⟨10.1038/ejhg.2010.172⟩. ⟨hal-00597450⟩