Ciliopathies Exome Sequencing Initiative

The study is aimed at identifying new genes involved in pediatric brain disorders from inbred families originating predominantly in the Middle East. Each patient analyzed to date has a specific and highly unique neurodevelopmental disorder that is likely to be recessive in nature. Many patients have one of the diseases along the "ciliopathy" spectrum of diseases, with evidence of kidney failure, retinal blindness and cerebellar ataxia.]]>
UCSD Adult Consent FormUCSD Parental Consent FormIRB Consent/Assent Documents ReviewIRB Waiver of Consent ReviewInclusion criteria: Proband from a family in which parents are 1st or 2nd degree cousins and there is two or more affected individuals in the family. The known genes involved in any similar disease have been excluded, either based upon direct sequencing of the gene, or by excluding the locus. There is adequate quantity of gDNA for analysis. Exclusion criteria: The individual DNA samples from the family must pass strict quality control steps to include: High quality DNA based upon OD 260/280 ratio, each sample must type properly for the assigned sex of the individual based upon X- and Y-chromosom markers, and each sample must show correct inheritance of polymorphic markers within the family. The family must not show a single linkage peak from genome-wide microarray data (otherwise we would use target-capture to identify the gene mutation). ]]>
Most of the genes in the genome are produce in the developing brain, but we do not know their function. Most of the human neurodevelopmental diseases do not have known causes. Therefore, we are trying to establish the spectrum of causes of neurodevelopmental diseases in humans, using a highly unique collection of families that we have ascertained over the past 10 years. In almost every instance, families show documented consanguinity (1st or 2nd cousin) with two or more affected individuals. In most instances, we have excluded mutations in known genes. The population gives us an opportunity to take advantage of next-generation sequencing in a straightforward and robust manner.]]>