JAMA ophthalmology · 2026
Prevalence of the Predisposing Gene MBD4 for Uveal Melanoma.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Le Ven Anaïs, Villy Marie-Charlotte, Le Mentec Marine, Houy Alexandre, Dubois d'Enghien Catherine, Matet Alexandre, Malaise Denis, Bubien Virginie, Lortholary Alain, Ait Omar Amal, Stoppa-Lyonnet Dominique, Cassoux Nathalie, Rodrigues Manuel, Golmard Lisa, Stern Marc-Henri, Colas Chrystelle
Аннотация
IMPORTANCE: MBD4 monoallelic germline pathogenic and likely pathogenic variants have recently been identified as predisposing to uveal melanoma, a rare primary intraocular tumor, with an estimated 9.15-fold increased risk of developing the disease for pathogenic variant carriers.
OBJECTIVE: To assess the risk of developing uveal melanoma for carriers of the MBD4 monoallelic germline pathogenic variant.
DESIGN, SETTING, AND PARTICIPANTS: In a case series involving 896 individuals, including 319 who were previously evaluated, germline target-sequencing of MBD4 was offered to every new patient with uveal melanoma at Curie Institute from February 2021 to September 2025. Non-Finnish European participants from the Genome Aggregation Database were used as a reference population.
EXPOSURE: Diagnosis of uveal melanoma genetic predisposition.
MAIN OUTCOMES AND MEASURES: Prevalence of MBD4 variants.
RESULTS: A total of 23 of 896 patients were identified as carrying an MBD4 germline pathogenic or likely pathogenic variant, corresponding to a relative risk of 31.44 (95% CI, 18.18-53.00) of developing uveal melanoma compared with the general population (2-sided Fisher exact test, P < .001).
CONCLUSIONS AND RELEVANCE: These findings confirm that MBD4 is an important predisposing gene to uveal melanoma in the French population. This reinforces a strategy of broad patient screening given the therapeutic implications and the consequences of genetic counseling.
OBJECTIVE: To assess the risk of developing uveal melanoma for carriers of the MBD4 monoallelic germline pathogenic variant.
DESIGN, SETTING, AND PARTICIPANTS: In a case series involving 896 individuals, including 319 who were previously evaluated, germline target-sequencing of MBD4 was offered to every new patient with uveal melanoma at Curie Institute from February 2021 to September 2025. Non-Finnish European participants from the Genome Aggregation Database were used as a reference population.
EXPOSURE: Diagnosis of uveal melanoma genetic predisposition.
MAIN OUTCOMES AND MEASURES: Prevalence of MBD4 variants.
RESULTS: A total of 23 of 896 patients were identified as carrying an MBD4 germline pathogenic or likely pathogenic variant, corresponding to a relative risk of 31.44 (95% CI, 18.18-53.00) of developing uveal melanoma compared with the general population (2-sided Fisher exact test, P < .001).
CONCLUSIONS AND RELEVANCE: These findings confirm that MBD4 is an important predisposing gene to uveal melanoma in the French population. This reinforces a strategy of broad patient screening given the therapeutic implications and the consequences of genetic counseling.