Authors declare no conflict of interest.
Mutations in ALDH1A3 cause microphthalmia
Article first published online: 27 MAY 2013
© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Volume 84, Issue 2, pages 128–131, August 2013
How to Cite
Mutations in ALDH1A3 cause microphthalmia., , , .
- Issue published online: 9 JUL 2013
- Article first published online: 27 MAY 2013
- Accepted manuscript online: 6 MAY 2013 10:03AM EST
- Manuscript Revised: 28 APR 2013
- Manuscript Accepted: 28 APR 2013
- Manuscript Received: 22 FEB 2013
- locus heterogeneity;
- retinoic acid
Microphthalmia is an important inborn error of eye development that can be associated with multisystem involvement. Anophthalmia is more severe and rarer. Single mutations in an expanding list of genes are known to cause this spectrum of anomaly. In one branch of a multiplex family with microphthalmia and anophthalmia, autozygome analysis excluded all known microphthalmia genes at the time of doing this study. Exome sequencing and autozygome filtration identified a novel homozygous variant in ALDH1A3. Subsequently, we identified another homozygous variant in 2 of the 10 probands with microphthalmia we specifically screened for mutations in ALDH1A3. Interestingly, the other branch of the original family was found to segregate anophthalmia/syndactyly with a novel homozygous SMOC1 variant. Our data support the very recent and independent identification of ALDH1A3 as a disease gene in microphthalmia. Locus heterogeneity should be considered in consanguineous families even for extremely rare phenotypes.