Germline mutations in BMP9 are not identified in a series of Danish and French patients with hereditary hemorrhagic telangiectasia

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Hereditary hemorrhagic telangiectasia (HHT), an inherited vascular disorder, is, in the majority of cases (85%), caused by mutations in one of three genes (ENG, ACVRL1, and SMAD4). In the remaining group of individuals with clinical HHT, mutations have not been identified, suggesting yet undiscovered HHT causative genes. A new vascular-anomaly syndrome caused by mutations in BMP9 has recently been published. Three patients suspected of HHT, with familial nose bleedings and dermal manifestations not characteristic for HHT, were described. Although, it was concluded that these patients probably had a different vascular-anomaly syndrome, the suspicion that BMP9 mutations might cause HHT remained. To evaluate if germline mutations in BMP9 can be identified in HHT patients, we investigated the Danish and the French Lyon cohort of mutation-negative and clinically definite HHT patients. Exons and exon-intron boundaries of BMP9 were analyzed by bi-directional Sanger sequencing in 28 clinical HHT patients (from 28 different families) with no pathogenic mutations in ENG, ACVRL1 or SMAD4. No mutations of potential pathogenicity were identified in BMP9. This study does not suggest that BMP9 mutations causes HHT, although this cannot be fully excluded based on this study. So far, we have been unable to identify any patients with clinical HHT caused by a BMP9 mutation. © 2016 Elsevier Inc.
OriginalsprogDansk
TidsskriftGene Reports
Vol/bind5
Sider (fra-til)30-33
ISSN2452-0144
DOI
StatusUdgivet - 2016

Citer dette

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title = "Germline mutations in BMP9 are not identified in a series of Danish and French patients with hereditary hemorrhagic telangiectasia",
abstract = "Hereditary hemorrhagic telangiectasia (HHT), an inherited vascular disorder, is, in the majority of cases (85{\%}), caused by mutations in one of three genes (ENG, ACVRL1, and SMAD4). In the remaining group of individuals with clinical HHT, mutations have not been identified, suggesting yet undiscovered HHT causative genes. A new vascular-anomaly syndrome caused by mutations in BMP9 has recently been published. Three patients suspected of HHT, with familial nose bleedings and dermal manifestations not characteristic for HHT, were described. Although, it was concluded that these patients probably had a different vascular-anomaly syndrome, the suspicion that BMP9 mutations might cause HHT remained. To evaluate if germline mutations in BMP9 can be identified in HHT patients, we investigated the Danish and the French Lyon cohort of mutation-negative and clinically definite HHT patients. Exons and exon-intron boundaries of BMP9 were analyzed by bi-directional Sanger sequencing in 28 clinical HHT patients (from 28 different families) with no pathogenic mutations in ENG, ACVRL1 or SMAD4. No mutations of potential pathogenicity were identified in BMP9. This study does not suggest that BMP9 mutations causes HHT, although this cannot be fully excluded based on this study. So far, we have been unable to identify any patients with clinical HHT caused by a BMP9 mutation. {\circledC} 2016 Elsevier Inc.",
author = "T{\o}rring, {P. M.} and S. Dupuis-Girod and S Giraud and K. Brusgaard and Ousager, {L. B.} and Kjeldsen, {A. D.}",
year = "2016",
doi = "10.1016/j.genrep.2016.08.005",
language = "Dansk",
volume = "5",
pages = "30--33",
journal = "Gene Reports",
issn = "2452-0144",
publisher = "Elsevier",

}

Germline mutations in BMP9 are not identified in a series of Danish and French patients with hereditary hemorrhagic telangiectasia. / Tørring, P. M.; Dupuis-Girod, S.; Giraud, S; Brusgaard, K.; Ousager, L. B.; Kjeldsen, A. D.

I: Gene Reports, Bind 5, 2016, s. 30-33.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Germline mutations in BMP9 are not identified in a series of Danish and French patients with hereditary hemorrhagic telangiectasia

AU - Tørring, P. M.

AU - Dupuis-Girod, S.

AU - Giraud, S

AU - Brusgaard, K.

AU - Ousager, L. B.

AU - Kjeldsen, A. D.

PY - 2016

Y1 - 2016

N2 - Hereditary hemorrhagic telangiectasia (HHT), an inherited vascular disorder, is, in the majority of cases (85%), caused by mutations in one of three genes (ENG, ACVRL1, and SMAD4). In the remaining group of individuals with clinical HHT, mutations have not been identified, suggesting yet undiscovered HHT causative genes. A new vascular-anomaly syndrome caused by mutations in BMP9 has recently been published. Three patients suspected of HHT, with familial nose bleedings and dermal manifestations not characteristic for HHT, were described. Although, it was concluded that these patients probably had a different vascular-anomaly syndrome, the suspicion that BMP9 mutations might cause HHT remained. To evaluate if germline mutations in BMP9 can be identified in HHT patients, we investigated the Danish and the French Lyon cohort of mutation-negative and clinically definite HHT patients. Exons and exon-intron boundaries of BMP9 were analyzed by bi-directional Sanger sequencing in 28 clinical HHT patients (from 28 different families) with no pathogenic mutations in ENG, ACVRL1 or SMAD4. No mutations of potential pathogenicity were identified in BMP9. This study does not suggest that BMP9 mutations causes HHT, although this cannot be fully excluded based on this study. So far, we have been unable to identify any patients with clinical HHT caused by a BMP9 mutation. © 2016 Elsevier Inc.

AB - Hereditary hemorrhagic telangiectasia (HHT), an inherited vascular disorder, is, in the majority of cases (85%), caused by mutations in one of three genes (ENG, ACVRL1, and SMAD4). In the remaining group of individuals with clinical HHT, mutations have not been identified, suggesting yet undiscovered HHT causative genes. A new vascular-anomaly syndrome caused by mutations in BMP9 has recently been published. Three patients suspected of HHT, with familial nose bleedings and dermal manifestations not characteristic for HHT, were described. Although, it was concluded that these patients probably had a different vascular-anomaly syndrome, the suspicion that BMP9 mutations might cause HHT remained. To evaluate if germline mutations in BMP9 can be identified in HHT patients, we investigated the Danish and the French Lyon cohort of mutation-negative and clinically definite HHT patients. Exons and exon-intron boundaries of BMP9 were analyzed by bi-directional Sanger sequencing in 28 clinical HHT patients (from 28 different families) with no pathogenic mutations in ENG, ACVRL1 or SMAD4. No mutations of potential pathogenicity were identified in BMP9. This study does not suggest that BMP9 mutations causes HHT, although this cannot be fully excluded based on this study. So far, we have been unable to identify any patients with clinical HHT caused by a BMP9 mutation. © 2016 Elsevier Inc.

U2 - 10.1016/j.genrep.2016.08.005

DO - 10.1016/j.genrep.2016.08.005

M3 - Tidsskriftartikel

VL - 5

SP - 30

EP - 33

JO - Gene Reports

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SN - 2452-0144

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