Genetic and clinical findings in a Chinese cohort with Leber congenital amaurosis and early onset severe retinal dystrophy

Br J Ophthalmol. 2020 Jul;104(7):932-937. doi: 10.1136/bjophthalmol-2019-314281. Epub 2019 Oct 19.


Background: Leber congenital amaurosis (LCA) and early onset severe retinal dystrophy (EOSRD) are clinically and genetically heterogeneous inherited retinal disorders that cause severe visual impairment in children. The objective of this study was to describe the mutation profile and phenotypic characteristics in Chinese patients with LCA or EOSRD.

Methods: Retrospective consecutive case series (2010-2017) study was performed in 148 probands (91 with LCA and 57 with EOSRD). All patients underwent ophthalmic evaluation. Mutations were revealed using targeted next-generation sequencing, followed by Sanger DNA-sequencing and real-time quantitative PCR analysis.

Results: We identified two diseasing-causing mutations in 88 unrelated patients, heterozygous autosomal dominant mutations in 11 probands and X-linked hemizygous mutations in 11 patients, for an overall mutation detection rate of 74.3% (110/148). We detected 158 different disease-causing mutations involving 14 LCA genes, 16 retinitis pigmentosa or cone-rod dystrophy genes and 3 syndromic retinal dystrophy genes. Of these 158 mutations, 98 were novel. The most common mutation was p.Q141X of AIPL1, with a gene-specific allele frequency of 60%. The first five most frequently mutated genes were AIPL1 (11.0%), RPGRIP1 (8.8%) and CEP290, GUCY2D and RPE65 (each 7.7%) in the patients with LCA and RPGR (12.3%), CRB1 (10.5%), RPE65 (10.5%), RDH12 (7.0%) and RP2 (5.3%) in the patients with EOSRD.

Conclusions: Our results revealed that the mutation spectrum of patients with LCA differs from that of the patients with EOSRD and established the configuration of the mutation frequencies for each LCA gene in Chinese patients, thereby providing essential information for future genetic counselling and gene therapy.

Keywords: Leber congenital amaurosis (LCA); early-onset severe retinal dystrophy (EOSRD); mutation spectrum; next generation sequencing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asian People / genetics*
  • Child, Preschool
  • China / epidemiology
  • Computational Biology
  • DNA Copy Number Variations
  • DNA Mutational Analysis
  • Exome Sequencing
  • Eye Diseases, Hereditary / genetics*
  • Eye Proteins / genetics*
  • Female
  • Gene Frequency
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Infant
  • Leber Congenital Amaurosis / genetics*
  • Male
  • Pedigree
  • Phenotype
  • Real-Time Polymerase Chain Reaction
  • Retinal Dystrophies / genetics*
  • Retrospective Studies
  • Visual Acuity / physiology
  • Young Adult


  • Eye Proteins

Supplementary concepts

  • Retinal Dystrophy, Early Onset Severe