Genotype-phenotype correlation in von Hippel-Lindau disease.
Adolescent
Adult
Aged
Aged, 80 and over
Child
DNA Mutational Analysis
Female
Fluorescein Angiography
/ methods
Follow-Up Studies
Fundus Oculi
Genetic Association Studies
/ methods
Genetic Predisposition to Disease
Germany
/ epidemiology
Hemangioblastoma
/ diagnosis
Humans
Male
Middle Aged
Morbidity
/ trends
Mutation
Retina
/ diagnostic imaging
Retinal Neoplasms
/ diagnosis
Retrospective Studies
Tomography, Optical Coherence
/ methods
Von Hippel-Lindau Tumor Suppressor Protein
/ genetics
Young Adult
von Hippel-Lindau Disease
/ complications
VHL
genotype -phenotype correlation
haemangioblastoma
retina
von Hippel-Lindau disease
Journal
Acta ophthalmologica
ISSN: 1755-3768
Titre abrégé: Acta Ophthalmol
Pays: England
ID NLM: 101468102
Informations de publication
Date de publication:
Dec 2021
Dec 2021
Historique:
revised:
24
11
2020
received:
10
08
2020
accepted:
23
02
2021
pubmed:
16
3
2021
medline:
15
1
2022
entrez:
15
3
2021
Statut:
ppublish
Résumé
Retinal haemangioblastomas (RH) remain a major cause of visual impairment in patients with von Hippel-Lindau (VHL) disease. Identification of genotype-phenotype correlation is an important prerequisite for better management, treatment and prognosis. Retrospective, single-centre cohort study of 200 VHL patients. Genetic data and date of onset of RH, central nervous system haemangioblastomas (CNSH), pheochromocytoma/paraganglioma (PPGL), clear cell renal cell carcinoma (ccRCC) and pancreatic neuroendocrine neoplasm (PNEN) were collected. The number and locations of RH were recorded. The first clinical finding occurred at an age of 26 ± 14 years (y) [mean ± SD]. In 91 ± 3% (95% CI 88-94) of the patients, at least one RH occur until the age of 60y. A total of 42 different rare VHL gene variants in 166 patients were detected. A higher age-related incidence of RH, CNSH, ccRCC and PNEN was detected in patients with a truncating variant (TV) compared to patients with a single amino-acid substitution/deletion (AASD) (all p < 0.01), while it is reverse for PPGL (p < 0.01). Patients with a TV showed 0.10 ± 0.15 RH per y during their lifetime compared to 0.05 ± 0.07 in patients with AASD (p < 0.02). The median enucleation/phthisis-free survival time in patients with a TV was 56y (95% CI 50-62) compared to 78y (95% CI 75-81) in patients with AASD (p < 0.02). Compared to patients with AASD, patients with a TV develop RH, CNSH, ccRCC and PNEN earlier. They experience a higher number of RH and bear a higher risk of enucleation/phthisis. Thus, patients with a TV might be considered for a more intensive ophthalmological monitoring.
Sections du résumé
BACKGROUND/AIMS
OBJECTIVE
Retinal haemangioblastomas (RH) remain a major cause of visual impairment in patients with von Hippel-Lindau (VHL) disease. Identification of genotype-phenotype correlation is an important prerequisite for better management, treatment and prognosis.
METHODS
METHODS
Retrospective, single-centre cohort study of 200 VHL patients. Genetic data and date of onset of RH, central nervous system haemangioblastomas (CNSH), pheochromocytoma/paraganglioma (PPGL), clear cell renal cell carcinoma (ccRCC) and pancreatic neuroendocrine neoplasm (PNEN) were collected. The number and locations of RH were recorded.
RESULTS
RESULTS
The first clinical finding occurred at an age of 26 ± 14 years (y) [mean ± SD]. In 91 ± 3% (95% CI 88-94) of the patients, at least one RH occur until the age of 60y. A total of 42 different rare VHL gene variants in 166 patients were detected. A higher age-related incidence of RH, CNSH, ccRCC and PNEN was detected in patients with a truncating variant (TV) compared to patients with a single amino-acid substitution/deletion (AASD) (all p < 0.01), while it is reverse for PPGL (p < 0.01). Patients with a TV showed 0.10 ± 0.15 RH per y during their lifetime compared to 0.05 ± 0.07 in patients with AASD (p < 0.02). The median enucleation/phthisis-free survival time in patients with a TV was 56y (95% CI 50-62) compared to 78y (95% CI 75-81) in patients with AASD (p < 0.02).
CONCLUSION
CONCLUSIONS
Compared to patients with AASD, patients with a TV develop RH, CNSH, ccRCC and PNEN earlier. They experience a higher number of RH and bear a higher risk of enucleation/phthisis. Thus, patients with a TV might be considered for a more intensive ophthalmological monitoring.
Substances chimiques
Von Hippel-Lindau Tumor Suppressor Protein
EC 2.3.2.27
VHL protein, human
EC 6.3.2.-
Types de publication
Comparative Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1492-e1500Subventions
Organisme : Dr. Gabriele Lederle-Stiftung
Organisme : Verein VHL (von Hippel-Lindau) betroffener Familien e.V.
Informations de copyright
© 2021 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.
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