Whole‐exome sequencing identified a novel homozygous ASPH frameshift variant causing Traboulsi syndrome in a Chinese family

Background Traboulsi syndrome is a rare disorder characterized by ectopia lentis and facial dysmorphism (large beaked nose), which was only reported in 18 individuals to date. It is caused by homozygous/compound heterozygous variants in the aspartate/asparagine‐β‐hydroxylase (ASPH) gene, which hydroxylates the aspartic acid and asparagine in epidermal growth factor‐like domains of various proteins. Methods Whole‐exome and Sanger sequencing were used to identify the disease‐causing gene of the patient in a consanguineous Chinese family. Domain analysis was applied to predict the impact of the variant on ASPH protein. Results Through exome and Sanger sequencing, we identified a novel homozygous ASPH variant (NM_004318.4:c.1910del/NP_004309.2: p.(Asn637MetfsTer15)) in the patient, which may lead to blockage of the ASPH function through truncating the AspH oxygenase domain of the ASPH protein and/or nonsense‐mediated decay of the ASPH transcript. This is the first report of Traboulsi syndrome in a Chinese patient who was combined with ventricular septal defect, lung bullae, and recurrent spontaneous pneumothorax. Conclusion Our results revealed the clinical characteristics of the first Chinese patient with Traboulsi syndrome. Additionally, our study expands the mutational spectrum of Traboulsi syndrome and provides information for clinical genetic counseling to this family. This is the first report of Traboulsi syndrome in a Chinses patient who was combined with recurrent spontaneous pneumothorax and ventricular septal defect. Our results revealed the clinical characteristics of the first Chinese patient with Traboulsi syndrome.