Genetics of Leber congenital amaurosis: an update

Abstract

Leber congenital amaurosis (LCA) is a hereditary condition involving severe visual loss or blindness that develops within the first year of life. LCA occurs as syndromic and nonsyndromic forms, and is mostly of autosomal-recessive inheritance. To date, mutations in 19 genes are known to be associated with nonsyndromic LCA phenotypes. Mutations in all known genes account for disease in 70% or less of LCA patients, suggesting that unidentified genes are responsible in the remaining cases. High-throughput screening methods such as mutation chips and exome sequencing have accelerated the pace of genetic discovery in LCA. Genetic testing is useful in counseling families and in confirming diagnosis in ambiguous cases. Gene-based therapy with the RPE65 gene has completed the first phase of clinical trials and shows promising results. Various other gene-specific and other modes of therapy are in experimental stages and are expected to progress to human trials in the near future.

Keywords::

• gene therapy
• genetics
• genotype–phenotype correlation
• LCA
• Leber congenital amaurosis
• mutations

Financial & competing interests disclosure

The authors are supported by the Hyderabad Eye Research Foundation, Champalimaud Foundation (Portugal) and by a grant from the Department of Biotechnology, Government of India. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.