Seven novel variants expand the spectrum of related Leber congenital amaurosis in the Chinese population.

PURPOSE

To screen in 187 families with Leber congenital amaurosis (LCA).

METHODS

Sanger sequencing and/or targeted exome sequencing was employed to identify mutations in the gene, and intrafamilial cosegregation analysis if DNA was available. In silico analyses and splicing assay were used to evaluate the variants' pathogenicity.

RESULTS

Genetic analysis revealed 15 mutations in in 14 pedigrees, including one splice-site mutation, one frameshift mutation, three nonsense mutations, and ten missense mutations. Of the mutations identified in , seven are novel associated with LCA, including five missense variants (c.124C>T, c.149T>C, c.340A>C, c.425A>G, and c.1399C>G) and two indel (insertions or deletions) variants (c.858+1delG and c.1181_1182insT). In vitro splicing assay was performed to evaluate the functional impact on RNA splicing of novel mutations if two of three in silico analyses were predicated to be non-pathogenic at the protein level. Among these 15 variants, 14 were classified as 'pathogenic variants,' and a variant (c.124C>T) was 'variants with uncertain significance' according to the standards and guidelines of the American College of Medical Genetics and Genomics.

CONCLUSIONS

Mutations in were responsible for 11 of the cohort of 187 Chinese families with LCA, which expands the spectrum of -related LCA in the Chinese population and potentially facilitates its clinical implementation.