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[P2.77]: A dlx‐wnt5a regulation modulates GABAergic differentiation of progenitor cells, in vitro and in vivo
Author(s) -
Merlo G.,
Paina S.,
Marino M.,
Garzotto D.,
DeMarchis S.,
Conti L.
Publication year - 2010
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/j.ijdevneu.2010.07.207
Subject(s) - humanities , library science , progenitor cell , art , biology , stem cell , computer science , microbiology and biotechnology
heterotopia, (non-TSC) focal dysplasia and polymicrogyria, were recruited in 15 years at our academic hospital. In an initial cohort of 113 patients, an etiological diagnosis was possible in 40% of the cases after systematic neuro-radiologic, clinical genetic, routine cytogenetic/FISH and molecular genetic tests (de Wit et al., Archives of Neurology, 2008). In DNA of additional 134 patients and parents, if available, analysis of copy number variations (CNV) was performed on Affymetrix 250K SNP arrays (CNAG program). CNVs were considered pathogenic if (1) not reported in the Toronto database (DGV) as polymorphic, (2) confirmed by independent techniques (FISH, Q-PCR), (3) included known microdeletion/duplication syndromes or (4) were de novo and included (candidate) genes, and (5) parents were available for testing. We identified pathogenic changes in about 13% of the patient samples, mostly from the polymicrogyria and heterotopia group. Additionally, a group of about 10 samples (7%) contained unclassified variants (UVs) including (1) inherited homozygous deletions/duplications from heterozygous parents, (2) deletions/duplications reported for rare and different clinical phenotypes. Analysis of candidate genes from these areas is ongoing in the patient cohort. Another approach to the identification of new genes for MCD using the same data set is represented by homozygosity mapping. In unrelated patients from consanguineous families we are pursuing analysis of overlapping genomic areas of homozygosity, in the assumption of autosomal recessive inheritance for rare MCD phenotypes. This approach gave us the opportunity to identify new syndromes associated with cortical brain malformations.