CIDR NICHD Genetic Basis of Recessive Pediatric Brain Disease - Group 3

The purpose of this study is to identify new genetic causes of recessive forms of pediatric neurodevelopmental disorders (NDDs) including Cerebellar hypoplasia (CBH), Lissencephaly (LIS), Microcephaly (MIC), Corpus callosum hypoplasia (CCH), Pontocerebellar hypoplasia (PCH), Pontine tegmental cap dysplasia (PTCD), and Aicardi syndrome among many others. Using whole exome sequencing (WES) on one or two affected members per family, we are able to identify many pathogenic genes for these families. Using Human SNP Linkage Scans, which takes advantage of the Illumina HumanCore Array, and parametric linkage analysis software (Genehunter, Allegro, and others), we seek to identify pathogenic loci utilizing 60-70 families per year. Through the combination of parametric linkage analysis with exome sequencing and bioinformatics approaches, we will refine our search for superior sensitivity and accuracy when investigating candidate genes and identifying causative mutations for disease.]]>
The inclusion criteria are these cases with likely inherited NDD for which the genetic cause is not known or is not obvious that falls within the Joubert syndrome spectrum to include the MESH terms listed. Parents must be consanguineous, and there must be more than one affected member per family. In some instances, these will be affected siblings and in other families this will be affected cousins. The exclusion criteria are those cases likely due to non-genetic factors such as environmental or pregnancy/labor/delivery issues, any cases with neurodegenerative components, or cases in which the genetic cause is obvious or already known.]]>
In 2000 we began to recruit families from the Middle East. We have identified several genes for Joubert syndrome and related disorders (JSRD) using homozygosity mapping. We expect that exome sequencing will increase the efficiency of gene discovery in these families.]]>