Hereditary hemorrhagic telangiectasia: two distinct ENG deletions in one family

作者：Wooderchak W; Gedge F; McDonald M; Krautscheid P; Wang X; Malkiewicz J; Bukjiok C J; Lewis T; Bayrak Toydemir P^*

来源：Clinical Genetics, 2010, 78(5): 484-489.

DOI：10.1111/j.1399-0004.2010.01418.x

• ACVRL1
• deletion
• ENG
• HHT

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterized by aberrant vascular development. Mutations in endoglin (ENG) or activin A receptor type II-like 1 (ACVRL1) account for around 90% of HHT patients, 10% of those are large deletions or duplications. We report here the first observation of two distinct, large ENG deletions segregating in one pedigree. An ENG exon 4-7 deletion was observed in a patient with HHT. This deletion was identified in several affected family members. However, some affected family members had an ENG exon 3 deletion instead. These deletions were detected by multiplex ligation-dependent probe amplification and confirmed by mRNA sequencing and an oligo-CGH array. Linkage analysis revealed that one individual with the exon 3 deletion inherited the same chromosome from his mother who has the exon 4-7 deletion. This finding has important clinical implications because it shows that targeted family-specific mutation analysis for exon deletions could have led to the misdiagnosis of some affected family members.

• 出版日期2010-11