Table 4 Molecular basis of low penetrance retinoblastoma
Type of mutation | Number of LP families | Description of mutations and frequency a | Functional consequences |
|---|---|---|---|
Regulatory | 3 | -198G>A (1/2) -188G>T (1/2) -149G>C (1/1) | Low expression of normal Rb protein |
MS point mutations | 12 | R661W (8/20) C712R (2/5) W563L (1/1) R787Q (1/1) | Partial inactivation of Rb protein |
Inframe deletion | 3 | Del:N480 (1/1) Del:E04 Del: E24–25 | Partial inactivation of Rb protein |
Splicing | 10 | 607+1G>T (4/11) 862-10T>C (1/1) 539+1delG, del E05 (1/1) 2325+5G>A, del E:22 (1/1) Q443P/del:E13 (1/1) V654L/splice (1/2) E732E/del E:21(1/2) | Alternative splicing and/or unessential exon skipping resulting in low expression or partial inactivation of Rb protein |
NS point mutation | 1 | Q675X (1/1) | Alternative splicing involving the stop codon |