Bilateral Retinoblastoma in a Male Patient with an X;13 Translocation: Evidence for Silencing of the RB1 Gene by the Spreading of X Inactivation

Abstract

et al. (1995) X-linked dilated cardiomyopathy: novel mutation of the dystrophin gene. Ann N Y Acad Sci 752:470-491 Klamut HJ, Bosnoyan-Collins LO, Worton RG, Ray PN, Davis HL (1996) Identification of a transcriptional enhancer within muscle intron 1 of the human dystrophin gene. Hum Mol Genet 5:1599-1606

Detection and reporting of RB1 promoter hypermethylation in diagnostic screening

“…There were two cell linesin one the X;13 translocation was balanced whilst the other was unbalanced. RB1 methylation is expected to be due to X chromosome inactivation spreading to chromosome 13 and inactivating an RB1 allele as previously reported (24).…”

“…As part of on-going quality checks we continue to test some tumours with two other pathogenic RB1 variants for promoter hypermethylation, and have yet to find another sample which also has promoter hypermethylation. 14m n/a n/a LOH 20 28 n/a n/a LOH 21 18 n/a n/a LOH 22 45 n/a n/a LOH 23 42 n/a n/a LOH 24 3 n/a n/a LOH 25 43 n/a n/a LOH 26 36 n/a n/a LOH 27 32 n/a n/a LOH 28 36 Multifocal /seeding? n/a n/a LOH 29 36 n/a n/a LOH 30 24 n/a n/a LOH 31 20 n/a n/a LOH 32 36 n/a n/a delRB1 33 11 n/a n/a delRB1 34 18 n/a n/a delRB1 35 42 n/a n/a delRB1 36 12 g.162,237 C>T Familial/germline c.2359C>T p.(R787*) and delRB1…”

Late Presentation of Retinoblastoma in a Teen with Aicardi Syndrome

“…Due to the presentation of a wide range of phenotypes and severities, X-chromosome inactivation (XCI) has been proposed as a probable cause of AS [2]. Several cases of XCI and 13q inactivation due to X:13 translocations have been reported in cases of Rb [6,8,9,10]. Thus, it would be interesting to determine if a combination of XCI and X:13 translocation could serve as a possible link between the Rb and AS.…”

Position effect of translocations involving the inactive X chromosome: physical linkage to XIC/XIST does not lead to long-range de novo inactivation in human differentiated cells

“…Given the reported long-range cis effect of the XIST gene in early development and the lack of requirement of X-specific elements for propagating the inactive state (Herzing et al, 1997;Lee and Jaenisch, 1997), there exists the possibility of cis inactivation of autosomal genes after de novo translocation to an Xi in differentiated cells. This seems to be the case in some constitutive translocations in mouse (Disteche et al, 1979) and for several human diseases (Puck and Willard, 1998), including cancer (Jones et al, 1997). However, humans do not tolerate extreme genetic imbalance (Keitges and Palmer, 1986;Schmidt and Du Sart, 1992).…”