Anophthalmia is a rare eye development anomaly resulting in absent ocular globes 
or tissue in the orbit since birth. Here, we investigated a newborn with 
bilateral anophthalmia in a Chinese family. Exome sequencing revealed that 
compound heterozygous mutations c.287G > A (p.(Arg96His)) and c.709G > A 
(p.(Gly237Arg)) of the ALDH1A3 gene were present in the affected newborn. Both 
mutations were absent in all of the searched databases, including 10,000 
in-house Chinese exome sequences, and these mutations were confirmed as having 
been transmitted from the parents. Comparative amino acid sequence analysis 
across distantly related species revealed that the residues at positions 96 and 
234 were evolutionarily highly conserved. In silico analysis predicted these 
changes to be damaging, and in vitro expression analysis revealed that the 
mutated alleles were associated with decreased protein production and impaired 
tetrameric protein formation. This study firstly reported that compound 
heterozygous mutations of the ALDH1A3 gene can result in anophthalmia in humans, 
thus highlighting those heterozygous mutations in ALDH1A3 should be considered 
for molecular screening in anophthalmia, particularly in cases from families 
without consanguineous relationships.