NAPG mutation in family members with hereditary hemorrhagic telangiectasia in China

Yu Xu, Yong-Biao Zhang, Li-Jun Liang, Jia-Li Tian, Jin-Ming Lin, Pan-Pan Wang, Rong-Hui Li, Ming-Liang Gu, Zhan-Cheng Gao
2021 BMC Pulmonary Medicine  
Background Hereditary hemorrhagic telangiectasia (HHT) is a disease characterized by arteriovenous malformations in the skin and mucous membranes. We enrolled a large pedigree comprising 32 living members, and screened for mutations responsible for HHT. Methods We performed whole-exome sequencing to identify novel mutations in the pedigree after excluding three previously reported HHT-related genes using Sanger sequencing. We then performed in silico functional analysis of candidate mutations
more » ... at were obtained using a variant filtering strategy to identify mutations responsible for HHT. Results After screening the HHT-related genes, activin A receptor-like type 1 (ACVRL1), endoglin (ENG), and SMAD family member 4 (SMAD4), we did not detect any co-segregated mutations in this pedigree. Whole-exome sequencing analysis of 7 members and Sanger sequencing analysis of 16 additional members identified a mutation (c.784A > G) in the NSF attachment protein gamma (NAPG) gene that co-segregated with the disease. Functional prediction showed that the mutation was deleterious and might change the conformational stability of the NAPG protein. Conclusions NAPG c.784A > G may potentially lead to HHT. These results expand the current understanding of the genetic contributions to HHT pathogenesis.
doi:10.1186/s12890-021-01524-4 pmid:34112136 pmcid:PMC8191015 fatcat:vdzwahjt5nf4lktqdtw6ypceei