PMID- 10625079
OWN - NLM
STAT- MEDLINE
DCOM- 20000120
LR  - 20190915
IS  - 0031-3998 (Print)
IS  - 0031-3998 (Linking)
VI  - 47
IP  - 1
DP  - 2000 Jan
TI  - Identification of hereditary hemorrhagic telangiectasia type 1 in newborns by
      protein expression and mutation analysis of endoglin.
PG  - 24-35
AB  - Hereditary hemorrhagic telangiectasia (HHT) is a dominantly inherited vascular
      disorder that is heterogeneous in terms of age of onset and clinical
      manifestations. Endoglin is the gene mutated in HHT1, which is associated with a 
      higher prevalence of pulmonary arteriovenous malformations than HHT2, where ALK-1
      is the mutated gene. Endoglin is constitutively expressed on endothelial cells
      and inducible on peripheral blood activated monocytes so that protein levels can 
      be measured by metabolic labeling and immunoprecipitation. We report the analysis
      of umbilical vein endothelial cells in 28 newborns from 24 families with a
      clinical diagnosis of HHT. Reduced levels of endoglin were observed in umbilical 
      vein endothelial cells in 15/28 subjects and in activated monocytes of all
      clinically affected relatives tested, suggesting that these individuals had HHT1.
      No mutant protein was expressed at the cell surface in any of these cases, and a 
      transient intracellular species was seen in samples of only two families,
      supporting a haploinsufficiency model. Quantitative multiplex PCR fragment
      analysis was established for the endoglin gene and revealed six mutations that
      were confirmed by automated DNA sequencing. An additional 10 mutations were
      identified in newborns by sequencing all exons. Of the 16 mutations, 10 were
      novel, three had been independently identified in related families, and three
      were previously known. Our data confirm that endoglin levels correlate with the
      presence or absence of mutation in HHT1 families, allowing the early
      identification of affected newborns that should be screened clinically to avoid
      serious complications of this disorder, such as cerebral arteriovenous
      malformations.
FAU - Cymerman, U
AU  - Cymerman U
AD  - Cancer and Blood Research Program, Hospital for Sick Children, Toronto, Canada.
FAU - Vera, S
AU  - Vera S
FAU - Pece-Barbara, N
AU  - Pece-Barbara N
FAU - Bourdeau, A
AU  - Bourdeau A
FAU - White, R I Jr
AU  - White RI Jr
FAU - Dunn, J
AU  - Dunn J
FAU - Letarte, M
AU  - Letarte M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Pediatr Res
JT  - Pediatric research
JID - 0100714
RN  - 0 (Antigens, CD)
RN  - 0 (ENG protein, human)
RN  - 0 (Endoglin)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Vascular Cell Adhesion Molecule-1)
SB  - IM
MH  - Antigens, CD
MH  - Cells, Cultured
MH  - Endoglin
MH  - Endothelium, Vascular/metabolism/pathology
MH  - Exons
MH  - Humans
MH  - Infant, Newborn
MH  - *Mutation
MH  - Polymorphism, Genetic
MH  - Receptors, Cell Surface
MH  - Telangiectasia, Hereditary Hemorrhagic/*diagnosis/genetics/pathology
MH  - Vascular Cell Adhesion Molecule-1/*genetics
EDAT- 2000/01/07 09:00
MHDA- 2001/03/28 10:01
CRDT- 2000/01/07 09:00
PHST- 2000/01/07 09:00 [pubmed]
PHST- 2001/03/28 10:01 [medline]
PHST- 2000/01/07 09:00 [entrez]
AID - 10.1203/00006450-200001000-00008 [doi]
PST - ppublish
SO  - Pediatr Res. 2000 Jan;47(1):24-35. doi: 10.1203/00006450-200001000-00008.