Genotype-phenotype correlations and clinical outcomes of patients with von Hippel-Lindau disease with large deletions.
J Med Genet
; 60(5): 477-483, 2023 05.
Article
en En
| MEDLINE
| ID: mdl-37080588
ABSTRACT
BACKGROUND:
Approximately 20%-40% of patients with von Hippel-Lindau (VHL) disease, an autosomal dominant hereditary disease, exhibit large deletions (LDs). Few studies have focused on this population. Hence, we aimed to elucidate the genotype-phenotype correlations and clinical outcomes in VHL patients with LDs.METHODS:
In this retrospective study, we included 119 patients with VHL disease from 50 unrelated families in whom LDs were detected using traditional and next-generation sequencing methods. Other germline mutations were confirmed by Sanger sequencing. Genotype-phenotype correlations and survival were analysed in different groups using Kaplan-Meier and Cox regression. We also evaluated therapeutic response to tyrosine kinase inhibitor (TKI) therapy.RESULTS:
The overall penetrance of patients aged <60 was 95.2%. Two VHL patients with LDs also carried CHEK2 and FLCN germline mutations. An earlier age of onset of retinal haemangioblastoma was observed in the next generation. Patients with exon 2 deletion of VHL had an earlier onset age of renal cell carcinoma and pancreatic lesions. The risk of renal cell carcinoma was lower in VHL patients with LDs and a BRK1 deletion. The group with earlier age of onset received poorer prognosis. Four of eight (50%) patients showed partial response to TKI therapy.CONCLUSION:
The number of generations and the status of exon 2 could affect age of onset of VHL-related manifestations. Onset age was an independent risk factor for overall survival. TKI therapy was effective in VHL patients with LDs. Our findings would further support clinical surveillance and decision-making processes.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Carcinoma de Células Renales
/
Enfermedad de von Hippel-Lindau
/
Neoplasias Renales
Tipo de estudio:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
J Med Genet
Año:
2023
Tipo del documento:
Article
País de afiliación:
China