A novel missense NMNAT1 mutation identified in a consanguineous family with Leber congenital amaurosis by targeted next generation sequencing

• A consanguineous family with suspected LCA is studied.
• Targeted next generation sequencing is performed to detect causative mutation.
• A novel missense mutation is identified to be pathogenic in the family.

Leber congenital amaurosis is the earliest onset and most severe inherited retinal dystrophy. Mutations in 21 genes have been identified to be responsible for LCA. To detect the causative variants, we performed targeted next generation sequencing in two affected siblings of a consanguineous Chinese family with suspected LCA. A novel homozygous missense mutation (c.721C>T, p. Pro241Ser) of NMNAT1 has been identified. The mutation was inherited from their consanguineous parents who were heterozygous and was absent in 300 unrelated healthy individuals. NMNAT1, which encodes the nicotinamide mononucleotide adenylyltransferase 1, has been recently identified to be one of the LCA-causing genes. Our results expanded the spectrum of mutations in NMNAT1. In this study, targeted next generation sequencing provides an accurate and efficient method for identifying mutations in hereditary diseases with highly genetic and clinical heterogeneity.