Array-CGH and clinical characterization in a patient with subtelomeric 6p deletion without ocular dysgenesis

Subtelomeric terminal 6p deletion has been recognized as a clinically identifiable syndrome including facial dysmorphism, malformation of the anterior eye chamber, hearing loss, heart defect and developmental delay. Genotype –phenotype correlations of previously published patients have been strongly suggested anterior eye segment anomalies as one of major malformation of the syndrome if the critical 6p25 region containing the FOXC 1 gene. In addition it has been hypothesized the presence in this region of one or more genes involved in hearing loss. We report on a case of terminal 6p deletion in a 47, XYY karyotype. Further characterization of the deletion with array comparative genome hybridization revealed also a cryptic microduplication on chromosome 19. The patient showed dysmorfic features, neuromotor retardation and profound language impairment, in absence of hearing loss and structural eye anomalies. As far as we know this is the first reported terminal 6p25.1 deletion case without eye dysgenesis precisely characterized by array-CGH. Our result could confirm that no genes in this region could be considered as an obvious candidate for hearing loss and demonstrate the need for further elucidation about function of the genes involved in eye developmental processes

Mutation frequencies of GNAQ, GNA11, BAP1, SF3B1, EIF1AX and TERT in uveal melanoma: detection of an activating mutation in theTERT gene promoter in a single case of uveal melanoma.

Background: Uveal melanoma is the most frequent primary tumor of the eye. It is molecularly clearly distinct from cutaneous melanoma and shows a different pattern of driver mutations. The influence of sunlight UV-exposure on the aetiology of uveal melanoma is matter of debate. The recent identification of driver mutations in the promoter of the telomerase reverse transcriptase (TERT) gene with UV induced cytidine-to-thymidine transitions in cutaneous melanoma prompted us to investigate whether these mutations also occur in uveal melanoma. Methods: We analysed 50 cases of uveal melanoma obtained from enucleation surgery for mutations in the genes GNAQ, GNA11, BAP1, SF3B1, EIFAX1 and TERT, measured gene expression using microarrays and analysed gene copy numbers by SNP arrays. Results: We detected a TERT mutation in only one case of a 57-year old white male with clinical and histopathological features typical for uveal melanoma. The tumor showed mutations in GNA11 and EIF1AX that are typical for uveal melanoma and absent from cutaneous melanoma. No mutations were detected in GNAQ, BAP1, and SF3B1 that are frequently mutated in uveal melanoma. Both copies of chromosome 3 were retained. Several tumors among which the one carrying the TERT promoter mutation showed elevated TERT expression. Consistent with previous reports GNAQ is inversely associated with chromosome 3 monosomy and metastasis. BAP1 mutations are significantly associated with chromosome 3 monosomy but not with relapse. Conclusion: These data indicate that TERT mutations are rare in uveal melanoma. No conclusion can be drawn on their potential influence on tumor progression