Next Generation Sequencing Reveals Genetic Basis for Congenital Cataracts

Applying the latest high-throughput, next-generation DNA sequencing technology has enabled researchers in the United Kingdom to diagnose children with rare diseases that are characterized by the formation of congenital cataracts.

Diagnosing which of the more than 100 diseases that cause between 20,000 and 40,000 cases of congenital cataracts each year is often a lengthy, costly, and inconclusive process based on numerous clinical assessments and a detailed family history.

Investigators at the University of Manchester (United Kingdom) decided to modernize this process by adapting the latest high-throughput DNA sequencing technology, which is capable of simultaneously scanning for mutations in all the 115 known congenital cataracts genes.

To verify this approach, the investigators evaluated samples from 36 patients and a known positive control. They were able to determine the precise genetic cause of congenital cataracts in 75% of individuals. Among the patient group, 85% were found to have likely pathogenic mutations, all of which occurred in highly conserved domains known to be vital for normal protein function. In one case, results of DNA sequencing aided in diagnosing a patient with Warburg Micro syndrome, an extremely rare disease that is marked by an abnormally small head and the development of severe epilepsy, among other medical issues.

"There are many diseases that involve congenital cataracts but finding the exact reason was always difficult," said contributing author Dr. Graeme Black, professor of genetics and ophthalmology at the University of Manchester. "Even with a family history, diagnosing these rare diseases was always a bit of a shot in the dark."

The DNA-based test, which was described in the August 19, 2014, online edition of the journal Ophthalmology, was certified for diagnostic use by the United Kingdom's National Health Service in December 2013.

Related Links:
University of Manchester