Mutations Causing CHIME Disease

Here is publication from Sanford-Burnham Medical Research Institute that uses Avadis NGS:

The goal in this paper is to find the underlying genomic cause of CHIME syndrome, a disease so rare that there are only 8 reported cases in the world. CHIME is an abbreviation derived from the main symptoms: Colobomas (hole in the eye), congenital Heart defects, Ichthyosiform dermatosis (scaling of skin), Mental retardation, and either Ear anomalies or Epilepsy.

They performed Exome sequencing (using the Nimblegen target enrichment kit) on 5 of the 8 reported cases; they also ran CGH arrays on a 6th reported case to identify gross copy number changes, and found a 1MB deletion on Chr 17. They focused on the 17 genes in this region for SNP analysis on the 5 Exome sequencing samples.

They found that only the PIGL gene in this region carried compound heterozygous mutations in all 5 samples. They also sequenced parents of these 5 cases and found that both parents were carriers in all cases (each parent had a mutation in one chromosomal copy).

This method provides an interesting glimpse into the future when genome sequencing is routine and the database of disease causing variants is comprehensive: the parents of these 8 cases would have realized that they are both carriers, and with a little investigation on the yet to be born babies, these cases may have been spared of their misery.