Hereditary hemorrhagic telangiectasia caused by mutation in intron 4 of ALK1 gene: analysis of a HTT family
To investigate the molecular pathogenesis of hereditary hemorrhagic telangiectasia (HHT). Peripheral blood samples were collected from a HTT family, including the proband, female, aged 48, and her mother, elder brother, elder sister, younger brother, and son. HHT gene mutations were identified by PCR-SSCP and DNA sequencing and confirmed by reverse sequencing. Ectopic transcripts of RT-PCR were used to confirm the characteristics of the mutation in non-canonical splicing site (IV S4 + 3 a > t). A mutational segment of PCR product of exon 4, exon-intron boundaries and the 3', 5' untranslated sequence of ALK1 gene was identified by PCR-SSCP. The mutational segment was analyzed by DNA sequencing. An IV S4 + 3 a > t mutation was found, causing splicing abnormality of intron 4 and exon 3 skipping. A splicing pattern of the IV S4 + 3 a > t mutation has been reported among Chinese HHT2 patients for the first time.