Background: Paediatric cataract is a rare disease characterised by opacity of the lens with onset at birth or during childhood. Known genes account for ~60% of cases, but as low as 20% in some reports particularly in non-European populations. There has been limited research on populations from low-income countries.
Aim: To determine the genetic causes of paediatric cataract in children from Myanmar.
Methods: Whole-exome sequencing was performed on DNA from saliva from 22 children (from 20 families) with cataract attending schools for the blind in Myanmar. A panel of 180 genes previously linked to cataract were screened for disease-causing variants as classified by the ACMG-AMP guidelines. A minigene splicing assay was performed to test alteration of splicing of a variant in SLC7A8.
Results: Pathogenic or likely pathogenic variants were identified in 45% (9/20) of probands including pathogenic variants in MIP, COL2A1, SLC7A8 and PAX6 and likely pathogenic in NHS, GJA8, GJA3, CRYGC. Most of these are well known cataract genes but COL2A1 and SLC7A8 are rarely reported. The COL2A1 variant was present in a child with a phenotype consistent with Stickler Syndrome and the SLC7A8 variant was co-inherited with a second variant (of uncertain significance), consistent with the reported recessive inheritance pattern. We also identified two variants of uncertain significance in CRYBB2 and one in GJA3 that are likely to be important, for a maximum diagnostic rate of 12/20 probands (60%).
Conclusion: This is the first study to examine the genetic aetiology of paediatric cataract in Myanmar. We report the genetic cause of cataracts in 45-60% of children for a genetic diagnostic rate comparable to reports in other populations and provide additional support for a role for COL2A1 and SLC7A8 in paediatric cataract.