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

• Published in: European journal of human genetics : EJHG 2011-02, Vol.19 (2), p.239-242
• Main Authors: Zollino, Marcella, Gurrieri, Fiorella, Orteschi, Daniela, Marangi, Giuseppe, Leuzzi, Vincenzo, Neri, Giovanni
• Format: Article
• Language: English
• Subjects: 631/154/555; 631/208/737; 692/1807/1693; 692/700/139; Abnormalities, Multiple - diagnosis; Abnormalities, Multiple - genetics; Abnormalities, Multiple - physiopathology; Adult and adolescent clinical studies; Bioinformatics; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Child, Preschool; Chromosome Deletion; Chromosomes, Human, Pair 6 - genetics; Comparative Genomic Hybridization; Cytogenetics; DNA-Binding Proteins - genetics; Epilepsy - diagnosis; Epilepsy - genetics; Female; Fundamental and applied biological sciences. Psychology; Gene Expression; General aspects. Genetic counseling; Genetics of eukaryotes. Biological and molecular evolution; Haploinsufficiency - genetics; Human Genetics; Humans; Intellectual deficiency; Intellectual Disability - diagnosis; Intellectual Disability - genetics; Language Development Disorders - diagnosis; Language Development Disorders - genetics; Medical genetics; Medical sciences; Membrane Proteins - genetics; Molecular and cellular biology; Polycomb-Group Proteins; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; ras GTPase-Activating Proteins - genetics; Short Report; Syndrome; Transcription Factors - genetics
• ISSN: 1018-4813; 1476-5438
• DOI: 10.1038/ejhg.2010.172

A de novo 0.3 Mb deletion on 6p21.3 was detected by array-comparative genomic hybridization 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 , which was recently demonstrated to cause non-syndromic 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. Similarly, 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 seizure control.