Variant distribution and characterization of hereditary hemorrhagic telangiectasia in Chinese patients

Abstract

Background: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder with variable manifestations, including recurrent epistaxis, telangiectasias, arteriovenous malformations, and family history. It is caused by heterozygous null alleles of ENG, ACVRL1, SMAD4, or BMP9, with delayed clinical diagnosis. Genetic testing is crucial for early diagnosis.

Objective: To analyze the variant distribution of HHT-related genes, expand variant databases for Chinese patients, and explore phenotype-genotype associations.

Methods: Thirty-two individuals from 20 unrelated families were recruited. Coding regions of ENG, ACVRL1, SMAD4, and BMP9 were sequenced. Variants were identified by sequence alignment. Epistaxis severity was evaluated using the epistaxis severity score (ESS), and the ESS differences between groups were analyzed using the Mann–Whitney test.

Results: Seventeen unique variants were identified in 17 unrelated HHT families (17/20, 85%), including 5 novel variants (3 in ENG and 2 in ACVRL1). Eleven ACVRL1 variants were identified in 12 families (12/17, 70.6%). Six variants of ENG were detected in 5 families (5/17, 29.4%), and one patient had two variants. ACVRL1 variants were 2.4 times more prevalent than ENG variants, with 41.7% of ACVRL1 variants in exon 10. A recurrent variant, c.1435C>T, was identified in two families. Epistaxis severity increased with age.

Conclusions: ACVRL1 variants were more common than ENG variants in Chinese HHT families, with exon 10 identified as a potential hotspot. These findings enhance understanding of HHT genetics and guide targeted genetic testing in China.

Keywords

ACVRL1 / ENG / epistaxis / Hereditary hemorrhagic telangiectasia / variants

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2025 The Author(s). Eye & ENT Research published by John Wiley & Sons Australia, Ltd on behalf of Higher Education Press.