Mutations cause eyes and face malformation

About 90% of human genes become active at various stages of normal eye and face development, and mutations in one of these genes may disrupt normal development.

Now, sequencing the genome of a Saudi Arabian individual, an international research team identified that mutations in a gene that encodes aspartyl β-hydroxylase (ASPH), an enzyme involved in hydroxylation of amino acids vital for normal development of the eyes and face, can cause Traboulsi syndrome, characterized by dislocated lens, eye cysts, flat cheeks and a beaked nose. 

The researchers corroborated the link between mutations in ASPH gene and Traboulsi syndrome by studying the gene’s mutations in two affected Lebanese individuals and mice. The mutations altered the structure of ASPH enzyme, leading to loss of its activity. 

In mice with an inactivated Asph gene, deficiency of ASPH enzyme caused them to develop shortened snouts, similar to the facial abnormalities of humans with Traboulsi syndrome. 

“Linking mutations in ASPH gene to Traboulsi syndrome will offer families options to avoid having more affected children through early prenatal diagnosis,” says Fowzan S. Alkuraya from the King Faisal Specialist Hospital and Research Centre, Riyadh, who led the study published in American Journal of Human Genetics¹.