Cheng Lei1,2,3, Ting Guo1,2,3, Shuizi Ding1,2,3, Liyan Liao4, Hong Peng1,2,3, Zhiping Tan5, Hong Luo1,2,3. 1. Department of Pulmonary and Critical Care Medicine, the Second Xiangya Hospital, Central South University, Changsha, China. 2. Research Unit of Respiratory Disease, Central South University, Changsha, China. 3. Hunan Diagnosis and Treatment Center of Respiratory Disease, Changsha, China. 4. Department of Pathology, the Second Xiangya Hospital, Central South University, Changsha, China. 5. Clinical Center for Gene Diagnosis and Therapy, Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Changsha, China.
Abstract
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.
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.
Authors: Nisha Patel; Arif O Khan; Ahmad Mansour; Jawahir Y Mohamed; Abdullah Al-Assiri; Randa Haddad; Xiaofei Jia; Yong Xiong; André Mégarbané; Elias I Traboulsi; Fowzan S Alkuraya Journal: Am J Hum Genet Date: 2014-04-24 Impact factor: 11.025
Authors: Jean-Marie Tschopp; Oliver Bintcliffe; Philippe Astoul; Emilio Canalis; Peter Driesen; Julius Janssen; Marc Krasnik; Nicholas Maskell; Paul Van Schil; Thomy Tonia; David A Waller; Charles-Hugo Marquette; Giuseppe Cardillo Journal: Eur Respir J Date: 2015-06-25 Impact factor: 16.671
Authors: Joseph E Dinchuk; Richard J Focht; Jennifer A Kelley; Nancy L Henderson; Nina I Zolotarjova; Richard Wynn; Nicola T Neff; John Link; Reid M Huber; Timothy C Burn; Mark J Rupar; Mark R Cunningham; Bernard H Selling; Jianhong Ma; Andrew A Stern; Gregory F Hollis; Robert B Stein; Paul A Friedman Journal: J Biol Chem Date: 2001-12-31 Impact factor: 5.157
Authors: Inga Pfeffer; Lennart Brewitz; Tobias Krojer; Sacha A Jensen; Grazyna T Kochan; Nadia J Kershaw; Kirsty S Hewitson; Luke A McNeill; Holger Kramer; Martin Münzel; Richard J Hopkinson; Udo Oppermann; Penny A Handford; Michael A McDonough; Christopher J Schofield Journal: Nat Commun Date: 2019-10-28 Impact factor: 14.919