• Incomplete penetrance of ALDH1A3 gene associated with autosomal recessive anophthalmia in a large consanguineous family
  • Masoud Dehghan Tezerjani,1,* Behdokht Fathi Dizaji,2 Mohammad Yahya Vahidi Mehrjardi,3
    1. Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Science, Yazd, Iran
    2. Department of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
    3. Department of Medical Genetics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran


  • Introduction: Anophthalmia and microphthalmia (A/M) are severe congenital defects of eye development. A variety of genetic and environmental factors contribute to A/M including mutations in the ALDH1A3 gene. These mutations cause autosomal recessive A/M mostly in consanguineous families of different ethnicities. Mutations in the genes have mainly shown full penetrance. Nevertheless, in this study, we present a case with homozygote mutation (c.709G>A) in the ALDH1A3 gene that was healthy without any eye abnormalities.
  • Methods: Before pregnancy, a 28-year-old woman without any clinical abnormality was referred to our center for genetic counseling since she had a 5-year-old boy suffering from non-syndromic bilateral anophthalmia. They were relative to a family in our previous study, where we detected a novel homozygous missense mutation (p. Gly237Arg) in exon 7 of the ALDH1A3 gene in the patients using whole exome sequencing. Accordingly, we checked the identified mutation in the case and her boy via Sanger sequencing. Next, we checked the mutation in her parents. Besides, we genotyped the cases bi-directionally in triplicate to verify the findings.
  • Results: The boy was homozygote for the mutation (c.709G>A) in the ALDH1A3 gene and showed bilateral anophthalmia. The mother was homozygote for the same mutation; however, she was healthy and did not show any eye abnormalities.
  • Conclusion: This case might present an incomplete-penetrance biallelic (c.709G>A) mutation in the ALDH1A3 gene.
  • Keywords: Anophthalmia; ALDH1A3; Incomplete penetrance