Identification and characterization of NMNAT1 gene mutations in an Iranian patient with Leber congenital amaurosis 9

Key Clinical Message The discovery of compound heterozygous NMNAT1 mutations (c.245T>C; p.Val82Ala and c.575A>G; p.Asp192Gly) provides a genetic explanation for Leber congenital amaurosis 9 in an Iranian patient. The proband's symptoms—including severe visual impairment, nystagmus, night blindness, and retinal degeneration—align with Leber congenital amaurosis 9 clinical features. This case underscores the value of exome‐sequencing in diagnosing rare genetic disorders and highlights its role in guiding personalized genetic counseling and potential treatments. Abstract Leber congenital amaurosis is a severe early‐onset inherited retinal dystrophy. This study delves into the genetic basis of Leber congenital amaurosis, pinpointing compound heterozygous mutations in the NMNAT1 gene as significant causative factors. While one mutation validates previous findings (c.245T>C; p.Val82Ala), the second (c.575A>G; p.Asp192Gly) proves novel, expanding the genetic landscape of Leber congenital amaurosis 9. Both mutations, inherited independently from nonconsanguineous parents, contribute to the intricate genetic basis of light on Leber congenital amaurosis 9 in this case. The identified mutations shed light on Leber congenital amaurosis genetics in the Iranian population, showcasing the efficacy of exome‐sequencing for molecular diagnoses in hereditary retinal degeneration. These findings provide valuable insights for tailored genetic counseling and potential therapeutic interventions.