Table 7. .
Laboratory Diagnostic Data for the Cohort of 29 FA-D2 Patients[Note]
| G2-Phase Arrest (%), G2/GF | Breaks/Cell | FANCD2 Mutation | ||||||||
| Patient Number | Kindred Sibling | Cell Type of Laboratory Diagnosis | Spontaneous | MMC/DEB | Spontaneous | MMC/DEB | Technique of Complementation Group Assignment | Allele 1 | Allele 2 | Somatic Mosaicism |
| 1 | 1/I | Lymphocyte | 65.7 | ND | .07 | 4.5 (MMC)/6.6 (MMC) | IB of LCL | c.696-121C→G (exonization) p.S232insQNNFX | c.696-121C→G (exonization) p.S232insQNNFX | None (residual protein) |
| 2 | 2/I | Lymphocyte | 54.3 | 70.1 (MMC) | .09 | 1.4 (MMC)/1.5 (DEB) | IB and RC of LCL | c.1948-6C→A (exon 22 skipping) p.E650X | c.3599delT p.I1200KfsX12 | None (residual protein) |
| 3 | 3/I | Lymphocyte (before mosaicism) | 38.6 (before mosaicism) | 46.6 (MMC) (before mosaicism) | .04 | .06 (MMC) | RC of fibroblasts | c.1948-16T→G (exon 22 skipping) p.E650X | c.1948-16T→G (exon 22 skipping) p.E650X | 1954G→A (exon 22), V652I, reconstitutes exon 22 recognition (blood, BM, LCL) |
| 4 | 4/I | Lymphocyte | 45.7 | 63.6 (MMC) | ND | ND | RC of fibroblasts | c.1948-16T→G (exon 22 skipping) p.E650X | c.1948-16T→G (exon 22 skipping) p.E650X | None (no LCL) |
| 5 | 4/II | Lymphocyte | 44.5 | 58.9 (MMC) | ND | ND | RC of fibroblasts | c.1948-16T→G (exon 22 skipping) p.E650X | c.1948-16T→G (exon 22 skipping) p.E650X | None (residual protein) |
| 6 | 5/I | Lymphocyte | 34.5 | 64.7 (MMC) | .05 | 4.7 (MMC)/ 5.6 (DEB) | IB and RC of LCL | c.274-57_−56insinvAluYb8nt36_319 +dup c.274–69_–57 (exon 5 skipping) p.I92YfsX7 | c.3803G→A p.W1268X | None (residual protein) |
| 7 | 6/I | Lymphocyte | 34.8 | 51.5 (MMC) | ND | ND | IB of LCL | c.904C→T p.R302W | c.1092G→A p.W364X | None (residual protein) |
| 8 | 7/I | Lymphocyte | 45.6 | 58.4 (MMC) | .06 | 1.3 (MMC) | IB of LCL | c.990-1G→A (aberrant splicing) p.S330RfsX16 | c.1948-6C→A (exon 22 skipping) p.E650X | None (residual protein) |
| 9 | 8/I | Lymphocyte | 65.3 | 70.9 (MMC) | .12 | ND | IB of LCL | c.810_812delGTC p.S271del | c.1948-16T→G (exon 22 skipping) p.E650X | None (residual protein) |
| 10 | 9/I | Lymphocyte | 38.4 | 58.4 (MMC) | ND | ND | RC of fibroblasts | c.1948-16T→G (exon 22 skipping) p.E650X | c.2715+1G→A (aberrant splicing) p.E906LfsX4 | None (residual protein) |
| 11 | 10/I | Lymphocyte | 55.4 | 65.8 (MMC) | ? (Wien) | ? (Wien) | IB of LCL | c.3707G→A (aberrant splicing) p.H1229EfsX7 | c.2835dupC p.D947RfsX3 | None (residual protein) |
| 12 | 11/I | Lymphocyte | 40.2 | 61.1 (MMC) | ND | ND | IB of LCL | c.274-57_–56insinvAlu Yb8nt36_319 +dup c.274–69_–57 p.I92YfsX7 | c.3453_3456delCAAA p.N1151KfsX46 | None (residual protein) |
| 13 | 12/I | Lymphocyte | 27.6 | 57.8 | .11 | 1.08 (MMC)/2.9 (DEB) | IB of LCL | c.1948-16T→G (exon 22 skipping) p.E650X | c.1948-16T→G (exon 22 skipping) p.E650X | None (residual protein in T cells and LCL) |
| 14 | 13/I | Lymphocyte fibroblast | 20.9 | 32.1 (MMC) | ND | ND | Mutation analysis (by sibling) | c.1948-6C→A (exon 22 skipping) p.E650X | 2775_2776CC→TT p.R926X | 2775_2776 CC (blood, LCL) |
| 15 | 13/II | Lymphocyte fibroblast | 25.0 | 35.4 (MMC) 69.2 (MMC) | 0 | .11 (MMC)/.02 (DEB) | RC of fibroblasts | c.1948-6C→A (exon 22 skipping) p.E650X | 2775_2776CC→TT p.R926X | Recombination |
| 16 | 14/I | Lymphocyte | ND | ND | .04 | 1.78 (DEB) | IB of LCL | c.2444G→A p.R815Q | c.2444G→A p.R815Q | None (residual protein) |
| 17 | 14/II | Lymphocyte | ND | ND | .12 | 3.1 (DEB) | Mutation analysis (by sibling) | c.2444G→A p.R815Q | c.2444G→A p.R815Q | None (no LCL) |
| 18 | 15/I | Lymphocyte | ND | ND | .12 | 1.5 (DEB) | IB of LCL | c.696-2A→T (exon 10 skipping) p.S232RfsX6 | c.1321_1322delAG (aberrant splicing) p.V379_K515del | None (residual protein) |
| 19 | 16/I | Fetal blood | ND | ND | ND | 3.7 (DEB) | RC of fetal fibroblasts | c.692T→Gpat p.L231R | c.2444G→Amat p.R815Q | Not done |
| 20 | 17/I | Lymphocyte | ND | ND | .02 | 8.4 (DEB) | IB and RC of LCL | c.1948–6C→Amat, (exon 22 skipping) p.E650X | 2660delApat p.E888RfsX16 | None (residual protein) |
| 21 | 18/I | Lymphocyte | ND | ND | .02 | 5.4 (DEB)10.3 (DEB) | IB of LCL | c.2404C→T p.Q802X | c.2444G→A p.R815Q | None (residual protein) |
| 22 | 19/I | Lymphocyte | ND | ND | .04 | 3.7 (DEB) | RC of fetal fibroblasts from 880/2 (early spontaneous abortion) | c.2444G→Apat p.R815Q | c.2715+1G→Amat (aberrant splicing) p.E906LfsX4 | None (residual protein) |
| 23 | 20/I | Lymphocyte | ND | ND | .08 | 7.4 (DEB) | IB of LCL | c.757C→T p.R253X | c.1367T→G p.L456R | None (residual protein) |
| 24 | 20/II | Lymphocyte | ND | ND | .20 | 8.9 (DEB) | IB of LCL | c.757C→T p.R253X | c.1367T→G p.L456R | None (residual protein) |
| 25 | 21 | Lymphocyte | ND | ND | Data missing | Data missing | Mutation analysis | c.1948–16T→G (exon 22 skipping) p.E650X | c.1948–16T→G (exon 22 skipping) p.E650X | 1953G→T (W651C) (blood, LCL) |
| 26 | 22/I | Fibroblast | 22.2 (fibroblast) | 54 (fibroblast, 300 nM ∼ 100 ng/ml MMC) | .04 | .16 (300 nM ∼ 100 ng/ml MMC) | Mutation analysis in fibroblasts (by sibling) | c.376A→G (aberrant splicing) p.S126RfsX12 | c.3803G→A p.W1268X | 376A (blood) |
| 27 | 22/II | Lymphocyte | ND | ND | .12 | >10 (MMC) | IB and IP of LCL | c.376A→G (aberrant splicing) p.S126RfsX12 | c.3803G→A p.W1268X | None (residual protein) |
| 28 | 23/I | Lymphocyte | ND | ND | .10 | 6.0 (MMC) | IB, IP and RC of LCL | c.206–2A→T (exon 4 skipping) p.A69DfsX7 | g.22875_23333del459 (c.1414–71_c.1545+256del459) p.E472_K515del | None (residual protein) |
| 29 | 23/II | Lymphocyte | ND | ND | .12 | 8.1 (MMC) | Mutation analysis (by sibling) | c.206-2A→T (exon 4 skipping) p.A69DfsX7 | g.22875_23333del459 (c.1414–71_c.1545+256del459) p.E472_K515del | None (residual protein) |
Note.— DEB=diepoxybutane; RC=retroviral complementation; IB=immunoblotting; IP=immunoprecipitation; ND=not determined; G2=G2 phase fraction of the cell cycle; GF=growth fraction; G2/GF=ratio G2 phase fraction over GF.