Clinical and molecular findings in a cohort of 152 Brazilian severe early onset inherited retinal dystrophy patients

Am J Med Genet C Semin Med Genet. 2020 Sep;184(3):728-752. doi: 10.1002/ajmg.c.31828. Epub 2020 Aug 31.

Abstract

Leber congenital amaurosis (LCA) and early-onset retinal dystrophy (EORD) are severe inherited retinal dystrophy that can cause deep blindness childhood. They represent 5% of all retinal dystrophies in the world population and about 10% in Brazil. Clinical findings and molecular basis of syndromic and nonsyndromic LCA/EORD in a Brazilian sample (152 patients/137 families) were studied. In this population, 15 genes were found to be related to the phenotype, 38 new variants were detected and four new complex alleles were discovered. Among 123 variants found, the most common were CEP290: c.2991+1655A>G, CRB1: p.Cys948Tyr, and RPGRIP1: exon10-18 deletion.

Keywords: Leber congenital amaurosis (LCA); causal genes; childhood blindness; early-onset retinal dystrophy (EORD); genotype-phenotype; pathogenic variants.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Antigens, Neoplasm / genetics*
  • Brazil / epidemiology
  • Cell Cycle Proteins / genetics*
  • Cytoskeletal Proteins / genetics*
  • Eye Diseases, Hereditary / diagnosis
  • Eye Diseases, Hereditary / epidemiology
  • Eye Diseases, Hereditary / genetics*
  • Eye Diseases, Hereditary / pathology
  • Eye Proteins / genetics*
  • Female
  • Genetic Association Studies
  • Genotype
  • Humans
  • Leber Congenital Amaurosis / diagnosis
  • Leber Congenital Amaurosis / epidemiology
  • Leber Congenital Amaurosis / genetics*
  • Leber Congenital Amaurosis / pathology
  • Male
  • Membrane Proteins / genetics*
  • Mutation / genetics
  • Nerve Tissue Proteins / genetics*
  • Pedigree
  • Phenotype
  • Retinal Dystrophies / diagnosis
  • Retinal Dystrophies / epidemiology
  • Retinal Dystrophies / genetics*
  • Retinal Dystrophies / pathology

Substances

  • Antigens, Neoplasm
  • CRB1 protein, human
  • Cell Cycle Proteins
  • Cep290 protein, human
  • Cytoskeletal Proteins
  • Eye Proteins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • RPGRIP1 protein, human

Supplementary concepts

  • Retinal Dystrophy, Early Onset Severe