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Novel mutations and polymorphisms in genes causing hereditary hemorrhagic telangiectasia
Author(s) -
Abdalla Salma A.,
Cymerman Urszula,
Rushlow Diane,
Chen Ning,
Stoeber Gwendolyn P.,
Lemire Edmond G.,
Letarte Michelle
Publication year - 2005
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.9312
Subject(s) - genetics , biology , exon , acvrl1 , gene , proband , nonsense mutation , mutation , missense mutation , intron , microbiology and biotechnology , endoglin , stem cell , cd34
Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant vascular disorder caused by mutations in Endoglin (ENG) or activin receptor‐like kinase‐1 ( ALK1, ACVRL1) genes. We performed molecular characterization in clinically affected probands of 31 HHT families and detected a total of 28 different mutations in the two genes, including four shared by more than one family. Twelve mutations were identified in the ENG gene, six of which were novel and comprised two nonsense mutations in exons 6 and 8, deletions in exons 5 and 11, and splice site mutations in exon 12 and intron 8. Eleven of sixteen mutations identified in the ALK1 gene were novel single base pair substitutions in exons 4, 7, 8, and 9. We also describe the first de novo ALK1 mutation that causes a previously unreported c.1133C>A substitution of a highly conserved residue (p.P378H). The proband and his two daughters, who also carried the familial mutation, all suffered from gastrointestinal (GI) bleeding. In addition, we report seven newly identified polymorphisms and summarize all known ones in both genes. © 2005 Wiley‐Liss, Inc.