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Leber Congenital Amaurosis in Asia

  • Sharola Dharmaraj
  • Anshuman Verma
  • P. Sundaresan
  • Chitra Kannabiran
Chapter
Part of the Essentials in Ophthalmology book series (ESSENTIALS)

Abstract

Leber congenital amaurosis (LCA) is a heterogeneous infantile retinal dystrophy presenting with severe visual loss, nystagmus, sluggish pupillary responses and an extinguished electroretinogram (ERG). LCA accounts for 5% of inherited retinal degenerative disorders worldwide. To date at least 30 genes are known to either cause or be associated with this condition. The genes perform a structural or functional role in the visual pathway. Mutations in several of these genes causing LCA have been identified in Asian populations (AIPL1, ALMS1, CABP4, CCT2, CEP290, CLUAP1, CRB1, CNGA3, CRX, CTNNA1, CYP4V2, GDF6, GUCY2D, IFT140, IMPDH1, IQCB1, KCNJ13, LCA5, LRAT, MERTK, MYO7A, NMNAT1, OTX2, PEX1, PNPLA6, POC1, PRPH2, RD3, RDH12, RPE65, RPGRIP1, SPATA7 and TULP1). An increased rate of consanguinity in some Asian populations has been noted, and gene identification using homozygosity mapping and testing for common mutations is possible, but the prevalence of mutations is not always identical to cohorts in the Western world. The advent of next-generation, whole genome and exome sequencing in addition to gene chip technology have revolutionised genetic and molecular diagnosis. Phenotype-genotype correlation of this disorder in some instances has made the choice of laboratory diagnosis rapid and easier. An accurate genetic diagnosis has become mandatory to access upcoming treatment options. Gene therapy for LCA has been encouraging recently as shown in the clinical trials involving RPE65-related LCA both in canines and humans.

Keywords

LCA RPE65 Clinical trials Gene therapy Consanguinity Mutations Asian Heterogeneity Genotype Phenotype Treatment Sequencing AIPL1 ALMS1 CABP4 CCT2 CEP290 CLUAP1 CRB1 CNGA3 CRX CTNNA1 CYP4V2 GDF6 GUCY2D IFT140 IMPDH1 IQCB1 KCNJ13 LCA5 LRAT MERTK MYO7A NMNAT1 OTX2 PEX1 PNPLA6 POC1 PRPH2 RD3 RDH12 RPE65 RPGRIP1 SPATA7 TULP1 

Notes

Acknowledgement

The authors would like to thank Desta Bokre of the Institute of Ophthalmology Library UCL, London UK for helping with the bibliography and references.

Compliance with Ethical Requirements

All authors declare that he/she has no conflict of interest.

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5). Informed consent was obtained from all patients for being included in the study.

No animal or human studies were carried out by the authors for this article.

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Online Resources

  1. Exome Variant ServerGoogle Scholar
  2. Human Mutation databaseGoogle Scholar
  3. Exome Aggregation ConsortiumGoogle Scholar
  4. ClinVar Databases.Google Scholar
  5. Leiden online variation databaseGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Sharola Dharmaraj
    • 1
  • Anshuman Verma
    • 2
  • P. Sundaresan
    • 2
  • Chitra Kannabiran
    • 3
  1. 1.Moorfields Eye HospitalLondonUK
  2. 2.Aravind Medical Research Foundation, Aravind Eye HospitalMaduraiIndia
  3. 3.LV Prasad Eye InstituteHyderabadIndia

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