[Clinical and genetic diagnosis in a hereditary hemorrhagic telangiectasia family].

To investigate the clinical features and feasibility genetic diagnosis in a hereditary hemorrhagic telangiectasia (HHT) family, and to explore the application of gene mutation testing in HHT diagnosis.

Methods

Medical histories and clinical features of a family were analyzed to diagnose HHT patients and suspected individuals according to the clinical diagnostic criteria. Sequence analysis of endoglin (ENG) and activin A receptor like type 1 (ACVRL1) gene in the proband was performed with PCR and Sanger sequencing technology. After the possible pathogenic mutation was identified in the proband, the specific mutation was detected in the suspected individuals and part of other family members. Then the genetic diagnoses were concluded.

Results

There were 5 family members in 4 generations manifested with epistaxis. According to the clinical diagnosis criteria, the proband with epistaxis, mucocutaneous telangiectases, visceral arteriovenous malformation and family history was diagnosed as HHT; while 2 survival family members with epistaxis and family history were suspected individuals. A substitution mutation in the 5'-untranslated region(5'-UTR) of ENG c.1-127 C>T was detected in the proband and the 2 suspected individuals, which did not exist in other family members. Based on the clinical and genetic findings, the 2 clinically suspected individuals were diagnosed as HHT.

Conclusion

There is great variability of the clinical manifestations among HHT patients. ENG c.1-127 C>T mutation is the possible pathogenic variant of the HHT family. A combination of clinical and genetic diagnosis could improve the diagnosis and treatment of HHT.