A novel mutation in the aspartate beta-hydroxylase (ASPH) gene is associated with a rare form of Traboulsi syndrome.

Traboulsi syndrome is a rare autosomal recessive genetic disorder. The present study aimed to identify the pathogenic variants in the ASPH gene responsible for a rare and unique presentation of Traboulsi syndrome associated with cardiac disorder. DNA was isolated from the blood samples from 3 clinically diagnosed Traboulsi syndrome patients (n = 3) after obtaining a prior-informed consent. All three had classical ocular and facial dysmorphic features, and two of them also had associated cardiac problems. Mutation screening was performed for the exons of ASPH gene by Sanger sequencing in these patients and 350 controls. Sequence data analysis was performed using Seqscape and insilico protein analysis by SIFT, PyMOL, and Dynamut softwares. A novel homozygous variant(c.1853 T > A) in exon 21 was identified by Sanger sequencing in two of the three cases while a known pathogenic variant in exon 25 was identified in the third proband. The novel nonsense variant in exon 21 results in a premature truncation of gene resulting in a protein of 543 amino acids. This variant is not reported in ExAC, dbSNP and 1000 genome databases. Both the patients harboring this novel variant, had a unique presentation of Traboulsi syndrome with cardiac dysfunction. In silico analysis predicted the mutation to affect the calcium-binding activity of the gene which might explain the associated cardiac dysfunction in these two patients. The novel pathogenic mutation displayed a perfect genotype-phenotype correlation in two probands of Traboulsi syndrome with cardiac dysfunction. [ABSTRACT FROM AUTHOR]