Clinical manifestations of patients with GDF2 mutations associated with hereditary hemorrhagic telangiectasia type 5.
GDF2
HHT5
hereditary hemorrhagic telangiectasia
Journal
American journal of medical genetics. Part A
ISSN: 1552-4833
Titre abrégé: Am J Med Genet A
Pays: United States
ID NLM: 101235741
Informations de publication
Date de publication:
01 2022
01 2022
Historique:
revised:
05
09
2021
received:
21
04
2021
accepted:
11
09
2021
pubmed:
7
10
2021
medline:
8
4
2022
entrez:
6
10
2021
Statut:
ppublish
Résumé
Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant fibrovascular dysplasia caused by mutations in ENG, ACVRL1, and SMAD4. Increasingly, there has been an appreciation for vascular conditions with phenotypic overlap to HHT but which have distinct clinical manifestations and arise from novel or uncharacterized gene variants. This study reported on a cohort of four unrelated probands who were diagnosed with a rare form of GDF2-related HHT5, for which only five prior cases have been described. Two patients harbored heterozygous missense variants not previously annotated as pathogenic (p.Val403Ile; p.Glu355Gln). Clinically, these patients had features resembling HHT1, including cerebrovascular involvement of their disease (first report documenting cerebral involvement of HHT5), but with earlier onset of epistaxis and a unique anatomic distribution of dermal capillary lesions that involved the upper forelimbs, trunk, and head. The other two patients harbored interstitial deletions larger than five megabases between 10q11.22 and 10q11.23 that included GDF2. To our knowledge, this is the first report detailing large genomic deletions leading to HHT5. These patients also demonstrated mucocutaneous capillary dysplasias, including intranasal vascular lesions complicated by childhood-onset epistasis, with a number of extravascular findings related to their 10q11.21q11.23 deletion. In conclusion, patients with GDF2-related HHT may present with a number of unique characteristics that differ from classically reported features of HHT.
Identifiants
pubmed: 34611981
doi: 10.1002/ajmg.a.62522
doi:
Substances chimiques
Endoglin
0
GDF2 protein, human
0
Growth Differentiation Factor 2
0
ACVRL1 protein, human
EC 2.7.11.30
Activin Receptors, Type II
EC 2.7.11.30
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
199-209Informations de copyright
© 2021 Wiley Periodicals LLC.
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