Pigmentary glaucoma (PG) typically impacts males in the third to fourth decade of life, but its roots have remained elusive—until now. Previous researchers have speculated that the condition had a heritable component, but were not able to identify the causative gene. Now, a Canada-based research team says it used whole exome sequencing of two independent pedigrees to identify two pre-melanosome protein (PMEL) variants associated with heritable PG as well as pigment dispersion syndrome (PDS)—from which PG stems. 

PMEL encodes a key component of melanosomes, the organelle essential for melanin synthesis, storage and transport, the investigators report. Targeted screening of PMEL in three independent sets identified seven additional PDS/PG-associated non-synonymous variants. Five of the nine variants exhibited defective processing of the PMEL protein.

Identifying these genes has the potential to be the first step in developing a gene therapy to combat the presently incurable disease. The team’s research also identified similarities with neurodegenerative disorders such as Alzheimer’s disease.

Lahola-Chomiak A, Footz T, Nguyen-Phuoc K, et al. Non-synonymous variants in premelanosome protein (PMEL) cause ocular pigment dispersion and pigmentary glaucoma. Human Molecular Genetics. December 17, 2018. [Epub ahead of print].