We collaboratively recruited over 2000 families, most with documented parental consanguinity, presenting a child with neurological disease. We performed exome sequencing on at least one affected member per family, then analyzed each for potentially deleterious homozygous mutations. GATK (DePristo et al., 2011) was used for variant identification and intersected with identity-by-descent blocks from HomozygosityMapper (Seelow et al., 2009). Rare potentially deleterious variants were prioritized against our cumulative in-house 4000 patient exome database and across publically available exome datasets, cumulatively numbering over 10,000 individuals. From this analysis, four independent consanguineous Turkish families with a neurodevelopmental/neurodegenerative disorder emerged (Figure 1A), all displaying an identical homozygous Chr.11:57427367G>A (hg19) single nucleotide transition in the CLP1 gene, resulting in a p.ARG140HIS (p.R140H) amino acid substitution mutation.
