Bilateral Uveal Melanoma: An Insight into Genetic Predisposition in Four New Unrelated Patients and Review of Published Cases.

Background: Primary bilateral uveal melanoma (BUM) is an exceptionally rare form of uveal melanoma (UM). This study aimed to explore the potential existence of a genetic predisposition towards the development of BUM. Methods: We employed an exome sequencing approach on germline DNA from four unrelated patients diagnosed with BUM, seeking pathogenic or likely pathogenic variants indicative of a genetic predisposition to UM. Results: None of the patients exhibited pathogenic variants in the BAP1 gene. However, loss-of-function (LoF) variants in the TERF2IP and BAX genes were identified in two of the BUM patients. For patients BUM1 and BUM2, no pathogenic/likely pathogenic variants of significant clinical relevance to BUM were found to warrant inclusion in this report. Conclusions: Our findings suggest the presence of yet-to-be-discovered genes that may contribute to UM predisposition, as evidenced by the absence of pathogenic variants in known UM predisposition genes among the four BUM patients studied. The TERF2IP and BAX genes emerge as noteworthy candidates for further investigation regarding their role in genetic predisposition to UM. Specifically, the potential role of UM as a candidate cancer within the spectrum of cancers linked to pathogenic variants in the TERF2IP gene and other genes associated with the shelterin complex warrants further examination. Additional functional studies are necessary to support or challenge this hypothesis.

Síndrome de Kallmann ligado al cromosoma X: heterogeneidad interfamiliar e intrafamiliar / X-linked Kallmann's syndrome: intra and interfamilial heterogeneity

Fundamento y objetivo: El síndrome de Kallmann se caracteriza por hipogonadismo hipogonadotropo y anosmia, y su forma ligada al cromosoma X se debe a mutaciones en el gen KAL1. Estudiamos a una familia con 6 miembros afectados por dicho síndrome. Pacientes y método: Comparamos las características clínicas (criptorquidia, micropene, pubertad, malformaciones asociadas), analíticas (test de la hormona liberadora de gonadotropinas y test de gonadotropina coriónica humana), genéticas (cariotipo) y radiológicas de los casos familiares con las de otros casos esporádicos de la bibliografía. Resultados: Los casos descritos eran portadores de la mutación R191X. Encontramos una gran heterogeneidad fenotípica entre los casos familiares y esporádicos de esta mutación. Conclusiones: Describimos los primeros casos conocidos de síndrome de Kallmann por la mutación R191X. Probablemente otros genes y/o factores epigenéticos influyen en el fenotipo

Background and objective: Hypogonadotropic hypogonadism and anosmia characterize Kallmann's syndrome, whose X-linked form is due to mutations in the KAL1 gene. We studied a family with 6 affected members. Patients and method: We compare their clinical (chryptorchidism, micropenis, puberty, associated malformations), analytical (gonadotrophin releasing hormone test, and human chorionic gonadotropin test), genetic (cariotype), and radiological data of the described familiar cases with other reported sporadic cases. Results: The described cases carried the R191X mutation. We found phenotypic heterogeneity between the patients. Conclusions: We report the first familiar cases of Kallmann's syndrome due to the R191X mutation. Probably other genes and/or epigenetic factors determine the phenotype