Identification of Two CRB1 and AHI1 Pathogenetic Variants in an Iranian Family with Two Syndromic and Non-Syndromic Inherited Retinal Disorders

Background: Leber congenital amaurosis (LCA) is one of the most common inherited retinal disorders characterized by rod-cone dystrophy nystagmus, strabismus, with decreased vision after birth, photophobia, cataracts and keratoconus. In the study, we found different genotypes in patients with two different non-syndromic and syndromic patterns in an Iranian family with autosomal recessive retinitis pigmentosa (arRP). Materials and methods: The proband’s variant were detected by Next Generation Sequencing (NGS) using True Sight One Clinical Exome (TSO) panel of 234 genes related to Inherited retinal dystrophies. The pathogenicity of the variants was determined based on their allele frequency in the Genome aggregation database (gnomAD), In silico prediction tools for new missense and splicing variants, following that it performed cosegregation data in the family. The variants were confirmed by Sanger sequencing using specific primers. Results: Molecular study of NGS and following sanger sequencing showed two variants in different CRB1 and AHI1 genes in the patients of family. In the study in proband (VI:2) revealed a homozygous frameshift variant in the exon 6 of the CRB1 gene (NM_201253.2; c.1576C>T; p. (Arg526*)) and in other member of the family a homozygous missense variant in the exon 15 of the AHI1 gene. Patients affected to LCA and a patient affected to Joubert syndrome (JBTS) presented different clinical features. Conclusions: In the present study. NGS is considered as the most new and powerful sequencing technique to detect causal variants in different genes. In the family identified two different molecular genetic characteristics of patients with (LCA) and mild JBTS which is involved retinal degeneration which are known to cause severe inherited retinal dystrophies.