Exome sequencing identifies a novel GUCY2D mutation in an Iranian family with Leber congenital amaurosis-1: a case report

Mostafa Neissi,Javad Mohammadi-Asl,Adnan Issa Al-Badran

doi:10.1186/s43042-022-00217-9

Abstract

BackgroundLeber congenital amaurosis (LCA), the severe form of inherited retinal degenerative disorder, is a prevalent disorder in the first year of life. Recently, genetic studies discovered that different gene mutations are responsible for LCA clinical manifestations.Case presentationIn this study, we applied whole exome sequencing (WES) to identify probable gene defects in an Iranian girl with LCA-1. We found a novel disease-causing GUCY2D gene mutation (c.2348T > C; p.L783P), located in exon 12 (NM_000180), causing a missense mutation that has been changed the coding protein. The WES-identified variant was confirmed by Sanger sequencing for the patient and her healthy parents. Submitted to genetic counseling that the patient was 1-year old and blindness from birth.ConclusionsOur findings establish that this detected GUCY2D-p.L783P mutation is the pathogenic variant for LCA-1. This is the first genetic study indicating that c.2348T > C missense mutation in the homozygous state in GUCY2D gene is responsible for the LCA-1 phenotype.

Highlights

Leber congenital amaurosis (LCA), the severe form of inherited retinal degenerative disorder, is a preva‐ lent disorder in the first year of life
Leber congenital amaurosis (LCA) is the most severe form of inherited retinal dystrophy that diagnosed with blindness or severe visual impairment before the first year of age [1, 2]
It has been identified that genetic abnormality in a group of genes included GUCY2D, RPE65, RPGRIP1, AIPL1, CRB1, NMNAT1, and CEP290 associated with LCA cases; more studies demonstrated that there are 26 genes related to the LCA [7, 8]