DNA alterations in patients with reversion of genotype +/− phenotype
| Disease | Nucleotide number normal→mutant→reverted aminoacid | Revertant cells | In vitro/in vivo | Type of reversion | Genotype | Reference |
|---|---|---|---|---|---|---|
| Changes in bold cannot be explained by currently accepted non-random mechanisms for site specific reversion. | ||||||
| Single nt, site specific reversion to normal of a single nucleotide; LCL, lymphoid cell lines. | ||||||
| *Parents not available for study and therefore mosaicism could be somatic mosaicism due to de novo mutation during a relatively late stage of embryogenesis with a selective advantage for original heterozygous normal cells. Conversely, reversion cannot be excluded. | ||||||
| †Note possible effect of PEG ADA in observed loss of revertant cells: reduction of toxic metabolites and eliminatiion of selective advantage for normal cells. | ||||||
| ‡The original t→a mutation results in a cryptic splice site and inclusion of 13 bp of intron into mRNA); a “second site” deletion of 11 bp that includes the cryptic splice site results in reversion to normal splicing | ||||||
| §Most reversions in Bloom syndrome are due to intragenic recombination, probably as a result of the basic pathology of the disease gene and are not included in this table. | ||||||
| Bp of intron results in use of normal splice site. | ||||||
| ¶In FANC C, 332delG is now called 67delG. | ||||||
| **6bp deletion associated with nucleotide change, resulting in use of original splice site. | ||||||
| In vivo is also used to designate that cells and or tissues were tested without culturing in vitro. | ||||||
| Tyrosinaaemia | 192 CAG→CAT→CAG 64 Gln→His→Gln | Liver nodule | Yes | Single nt | Homozygous | 17 |
| Abnormal splice 1009GGC→AGC→GGC 337 Gly→Ser→Gly | Liver nodule | Yes | Single nt | Homozygous | 17 | |
| IVS12+5 G→A→G | Liver nodule | Yes | Single nt | Heterozygous | 17 | |
| IVS12+5 G→A→G | Liver nodule | Yes | Single nt | Heterozygous | 17 | |
| IVS12+5 G→A→G | Liver nodule | NA/yes | Single nt | Homozygous | 18 | |
| 836 CAG→CGG→CAG 279 Gln→Arg→Gln | Liver nodule | Yes/yes | Single nt ?CpG hotspot | Heterozygous | 19 | |
| ADA-SCID (severe combined immuno-deficiency) | IVS1 +1g→c→g* | B cells/PBL | Yes/yes | Single nt | Heterozygous | 22* |
| 467 CGC→CAC→CGC 156 Arg→His→Arg | B cells/ PBL | Yes/yes | Single nt | Heterozygous | 23 | |
| 355 CAG→TAG→CAG 119 Gln→Stop→Gln | T cells | Yes/yes | Single nt | Heterozygous | 24 | |
| 704 CGG→CAG→CGG 235 Arg→Gln→Arg | T cells | Yes/no† | Single nt | Heterozygous | 24 | |
| IVS11-15t→a‡ (cryptic splice)→del −4 to −14 IVS11‡ | B cells/PBL | Yes/yes | Second site mutation | Homozygous | 25 | |
| X linked SCID | 343 TGT→CGT→TGT 115 Cys→Arg→Cys | T cells (sorted) | Yes/yes | Single nt ?hot spot CpG | Hemizygous | 32 |
| Wiskott-Aldrich (X linked) | 354 TAC→TGC→TAC 107 Tyr→Cys→Tyr | T cells | Yes/yes | Single nt | Hemizygous | 40 |
| [ACGAGG]→434ins6 bp/del 6 bp | T cells | Yes/yes | Del repeat | Hemizygous | 41 | |
| 1131G→del 1131G→[del G+ins1100A] | Lymphocytes | NT/yes | Second site mutation | Hemizygous | 42 | |
| Bloom Syndrome§ | 1544 9As→10As (insA)→9As (delA) | Fibroblast, PBL | Yes/yes | ?Slippage | Homozygous | 44 |
| 2702 TGT→TAT→TGT 901 Cys→Tyr→Cys | LCL | Yes/yes | Single nt (father NT) | Homozygous | 44 | |
| Epidermolysis bullosa | ||||||
| COL 17A1 | 1706A→del 1706A→ins1706A | Skin cells only | Yes/yes | Mitotic gene conversion | Heterozygous | 45 |
| COL 17A1 | 4003TC→delTC→delTC+ins4080GG | Skin (laser dissected) | ?Yes/yes | Second site del/ins | Homozygous | 46 |
| Keratin 14 | IVS1 −2a→c | Skin | Yes/yes | **Pseudogene | Homozygous | 47 |
| Fanconi anaemia | ||||||
| FANC A | 1615G→1615delG→1615delg1637delA1641delT | Blood cells, LCLs | Yes/? | Second site deletions | Homozygous | 50 |
| 3559→3559insG→3559insG3580insCGCTG | Blood cells, LCL | Yes/? | Second site insertions | Homozygous | 50 | |
| 2815 Ins19 bp→del ins 19BP | Haematopoietic cells (?stem cell) | Yes/?yes | Ins/del repeat hot spot | Heterozygous | 53 | |
| 856 CAG→TAG→CAG 256 Gln→Stop→Gln | Blood cells, LCL | Yes/?yes | Single nt | Heterozygous | 51 | |
| 862 GAG→TAG→GAG288 Glu→Stop→Glu | Blood cells, LCL | Yes/?yes | Single nt | Heterozygous | 51 | |
| 971 CTG→CGG→CTG324 Leu→Arg→Leu | Blood cells, LCL | Yes/yes | Single nt | Heterozygous | 51 | |
| 2852 CGG→CAG→CGG 951 Arg→Gln→Arg | Blood cells, LCL | Yes/?yes | Single nt & repeat ?slippage | Heterozygous | 51 | |
| FANC C | 322delG¶/1806insA→ wild-type with absence of both mutations in a clone | Blood cells LCL | — | Intragenic recombination | Heterozygous | 50 |
| 322G→→322delG¶→322G | Blood cells LCL | Yes/yes | Not intragenic recombination | Heterozygous | 50 | |
| Sib of above: same changes | ||||||
| 1749 CTT→CGT→TGT 496 Leu→Arg→Cys | Blood cells LCL | Yes | Second site ?CpG hot spot | — | 52 | |
| 67delG ¶ | — | — | Intragenic recombination | Heterozygous | 51 | |