Hereditary hemorrhagic telangiectasia: two distinct ENG deletions in one family.
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.
Wooderchak
W
W
ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, UT, USA.
Gedge
F
F
McDonald
M
M
Krautscheid
P
P
Wang
X
X
Malkiewicz
J
J
Bukjiok
C J
CJ
Lewis
T
T
Bayrak-Toydemir
P
P
D030301:Activin Receptors, Type II / Q000235:genetics; D000328:Adult; D015703:Antigens, CD / Q000235:genetics*; D004200:Diseases in Twins; D000071063:Endoglin; D005260:Female; D006801:Humans; D008297:Male; D010375:Pedigree; D011956:Receptors, Cell Surface / Q000235:genetics*; D017384:Sequence Deletion; D013683:Telangiectasia, Hereditary Hemorrhagic / Q000235:genetics*
D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D011956:Receptors, Cell Surface; C425364:ACVRL1 protein, human; D030301:Activin Receptors, Type II