Sasaki Y, Margolin Z, Borgo B, Havranek JJ, Milbrandt J. Characterization of Leber’s Congenital Amaurosis-associated NMNAT1 Mutants. J Biol Chem. 2015 May 27. pii: jbc.M115.637850. [Epub ahead of print] PMID: 26018082
In this paper, we used a series of assays to identify Nmnat1 functional deficits caused by mutations in this NAD biosynthetic enzyme that result in a childhood retinal degeneration disorder called Leber Congenital Amaurosis 9.
Background: LCA9 is a severe retinal degeneration condition caused by mutations in the NAD + biosynthetic enzyme NMNAT1.
Results: Many of LCA9-associated NMNAT1 mutants have relatively normal enzymatic and neuroprotective activities, but manifest stress- induced instability.
Conclusion: Stress-induced instability of NMNAT1 could be responsible for retinal abnormalities in LCA9.
Significance: Our results identify potential mechanisms that promote retinal degeneration observed in LCA9.