Document Detail


Integrated analysis of clinical signs and literature data for the diagnosis and therapy of a previously undescribed 6p21.3 deletion syndrome.
MedLine Citation:
PMID:  21119708     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Marcella Zollino; Fiorella Gurrieri; Daniela Orteschi; Giuseppe Marangi; Vincenzo Leuzzi; Giovanni Neri
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Publication Detail:
Type:  Case Reports; Journal Article     Date:  2010-12-01
Journal Detail:
Title:  European journal of human genetics : EJHG     Volume:  19     ISSN:  1476-5438     ISO Abbreviation:  Eur. J. Hum. Genet.     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-01-13     Completed Date:  2011-05-04     Revised Date:  2012-02-01    
Medline Journal Info:
Nlm Unique ID:  9302235     Medline TA:  Eur J Hum Genet     Country:  England    
Other Details:
Languages:  eng     Pagination:  239-42     Citation Subset:  IM    
Affiliation:
Istituto di Genetica Medica, Università Cattolica Sacro Cuore, Policlinico A. Gemelli, Roma, Italy. mzollino@rm.unicatt.it
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MeSH Terms
Descriptor/Qualifier:
Abnormalities, Multiple / diagnosis*,  genetics,  physiopathology*
Child, Preschool
Chromosome Deletion*
Chromosomes, Human, Pair 6 / genetics
Comparative Genomic Hybridization
DNA-Binding Proteins / genetics
Epilepsy / diagnosis,  genetics
Female
Haploinsufficiency / genetics
Humans
Intellectual Disability / diagnosis,  genetics*
Language Development Disorders / diagnosis,  genetics
Membrane Proteins / genetics
Syndrome
Transcription Factors / genetics
ras GTPase-Activating Proteins / genetics
Chemical
Reg. No./Substance:
0/CUTA protein, human; 0/DNA-Binding Proteins; 0/Membrane Proteins; 0/PHF1 protein, human; 0/SYNGAP1 protein, human; 0/Transcription Factors; 0/ras GTPase-Activating Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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