Cerebral Cavernous Malformations (CCMs) are vascular anomalies mostly located in the CNS, affecting up to 0.5% of the population that occur sporadically or inherited in an autosomal dominant fashion with a high penetrance. Whereas sporadic cases often present a single lesion, the familial form, usually are characterized by a presence of multiple lesions and have been associated with mutations in KRIT1/CCM1, MGC4607/CCM2 and PDCD10/CCM3 genes. About 50% of familial cases harbored a mutation in KRIT1, 18% in MGC4607 and 10% in PDCD10, whereas in the 22% of them and in a larger proportion of sporadic cases with multiple lesions no mutations were detected. In addition, the PDCD10 proportion was much lower than expected, based on previous linkage data which suggested that 40% of CCM families were linked to the locus CCM3 (1). These data suggest the existence of additional non identified CCM genes, possibly located close to PDCD10. Here, we focus our attention on SERPINI1 gene, closely near PDCD10 and separated from the latter by a short region of 851 bp acting as bidirectional promoter for the two adjacent genes. In fact, it regulates SERPINI1 expression in forward and PDCD10 one in reverse, despite these are two non-homologous genes. Through an in-silico approach, we wanted to investigate the existence of pathways common to both genes in order to explain the need of this co-regulation and detect a possible involvement of SERPINI1 in CCM pathogenesis. hen, we went on to SERPINI1 molecular analysis on a cohort of 65 CCM negative patients recruited by us in recent years 1. Liquori C.L. et al. “Hum Mutat” 2006

Two non-homologous co-regulated genes PDCD10 and SERPINI1: any possible related function?

C. Scimone;RINALDI, Carmela;RUGGERI, ALESSIA;L. Donato;D'ANGELO, Rosalia;SIDOTI, Antonina
2014-01-01

Abstract

Cerebral Cavernous Malformations (CCMs) are vascular anomalies mostly located in the CNS, affecting up to 0.5% of the population that occur sporadically or inherited in an autosomal dominant fashion with a high penetrance. Whereas sporadic cases often present a single lesion, the familial form, usually are characterized by a presence of multiple lesions and have been associated with mutations in KRIT1/CCM1, MGC4607/CCM2 and PDCD10/CCM3 genes. About 50% of familial cases harbored a mutation in KRIT1, 18% in MGC4607 and 10% in PDCD10, whereas in the 22% of them and in a larger proportion of sporadic cases with multiple lesions no mutations were detected. In addition, the PDCD10 proportion was much lower than expected, based on previous linkage data which suggested that 40% of CCM families were linked to the locus CCM3 (1). These data suggest the existence of additional non identified CCM genes, possibly located close to PDCD10. Here, we focus our attention on SERPINI1 gene, closely near PDCD10 and separated from the latter by a short region of 851 bp acting as bidirectional promoter for the two adjacent genes. In fact, it regulates SERPINI1 expression in forward and PDCD10 one in reverse, despite these are two non-homologous genes. Through an in-silico approach, we wanted to investigate the existence of pathways common to both genes in order to explain the need of this co-regulation and detect a possible involvement of SERPINI1 in CCM pathogenesis. hen, we went on to SERPINI1 molecular analysis on a cohort of 65 CCM negative patients recruited by us in recent years 1. Liquori C.L. et al. “Hum Mutat” 2006
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11570/3004370
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