High-throughput genetic analysis in a cohort of patients with Ocular Developmental Anomalies

  1. Suganya Kandeeban1,
  2. Sudha Karthikeyan1,
  3. Karthiyayini Thirumalai1,
  4. Meenakshi Swaminathan2,
  5. Sumita Agarkar2,
  6. Nirmala Subramian3 ,
  7. Sripriya Sarangapani1

Authors Affiliation(s)

  • 1SN ONGC Department of Genetics and Molecular Biology, Vision Research Foundation, Chennai, INDIA
  • 2Department of Paediatric Ophthalmology, Medical Research Foundation, Chennai, INDIA
  • 3Department of Orbit and Oculoplasty, Medical Research Foundation, Chennai, INDIA

Can J Biotech, Volume 1, Special Issue, Page 92, DOI: https://doi.org/10.24870/cjb.2017-a79

Presenting author: sugan.kandeeban@gmail.com


Anophthalmia and microphthalmia (A/M) are developmental ocular malformations in which the eye fails to form or is smaller than normal with both genetic and environmental etiology. Microphthalmia is often associated with additional ocular anomalies, most commonly coloboma or cataract [1, 2]. A/M has a combined incidence between 1-3.2 cases per 10,000 live births in Caucasians [3, 4]. The spectrum of genetic abnormalities (chromosomal and molecular) associated with these ocular developmental defects are being investigated in the current study. A detailed pedigree analysis and ophthalmic examination have been documented for the enrolled patients followed by blood collection and DNA extraction. The strategies for genetic analysis included chromosomal analysis by conventional and array based (affymetrix cytoscan HD array) methods, targeted re-sequencing of the candidate genes and whole exome sequencing (WES) in Illumina HiSEQ 2500. WES was done in families excluded for mutations in candidate genes. Twenty four samples (Microphthalmia (M)-5, Anophthalmia (A)-7,Coloboma-2, M&A-1, microphthalmia and coloboma / other ocular features-9) were initially analyzed using conventional Geimsa Trypsin Geimsa banding of which 4 samples revealed gross chromosomal aberrations (deletions in 3q26.3-28, 11p13 (N=2) and 11q23 regions). Targeted re sequencing of candidate genes showed mutations in CHX10, PAX6, FOXE3, ABCB6 and SHH genes in 6 samples. High throughput array based chromosomal analysis revealed aberrations in 4 samples (17q21dup (n=2), 8p11del (n=2)). Overall, genetic alterations in known candidate genes are seen in 50% of the study subjects. Whole exome sequencing was performed in samples that were excluded for mutations in candidate genes and the results are discussed.


  1. Williamson, K.A. and FitzPatrick, D.R. (2014) The genetic architecture of microphthalmia, anophthalmia and coloboma. Eur J Med Genet 57: 369380. Crossref
  2. Skalicky, S.E., White, A.J., Grigg, J.R., Martin, F., Smith, J., Jones, M., Donaldson, C., Smith, J.E., Flaherty, M. and Jamieson, R.V. (2013) Microphthalmia, anophthalmia, and coloboma and associated ocular and systemic features: understanding the spectrum. JAMA Ophthalmol 131: 15171524. Crossref
  3. Morrison, D., FitzPatrick, D., Hanson, I., Williamson, K., van Heyningen, V., Fleck, B., Jones, I., Chalmers, J. and Campbell, H. (2002) National study of microphthalmia, anophthalmia, and coloboma (MAC) in Scotland: investigation of genetic aetiology. J Med Genet 39: 1622. Crossref
  4. Shah, S.P., Taylor, A.E., Sowden, J.C., Ragge, N.K., Russell-Eggitt, I., Rahi, J.S. and Gilbert, C.E.; Surveillance of Eye Anomalies (SEA-UK) Special Interest Group (2011) Anophthalmos, microphthalmos, and typical coloboma in the United Kingdom: a prospective study of incidence and risk. Invest Ophthalmol Vis Sci 52: 558564. Crossref