Table 1.
Clinical information and the results of this study.
| Patient number | Patient 1 | Patient 2 | Son of patient 2 | Patient 3 | Patient 4 | Daugther of patient 4 | Mother of patient 4 | Patient 5 | Patient 6 | Patient 7 | Patient 8 | Patient 9 | Patient 10 | Patient 11 | Patient 12 | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Gender | F | M | M | F | M | F | F | M | F | F | M | F | F | F | M | |
| Age at examination | 47 y | 39 y | 8 m | 2 m | 68 y | 31 y | 89 y | 69 y | 19 y | 16 y | 28 y | 15 y | 68 y | 14 y | 8 y | |
| Family history | − | + | + | − | + | + | + | + | + | − | + | − | NA | + | − | |
| Clinical features | ||||||||||||||||
| Splenomegaly | − | − | − | NA | NA | + | − | + | − | − | + | − | + | − | NA | |
| Splenectomy | − | + | − | − | NA | NA | NA | − | − | − | − | − | − | + | − | |
| Gallstone | NA | + | NA | − | NA | NA | NA | + | NA | NA | NA | − | + | NA | + | |
| Previous blood transfusion | − | + | − | + | − | NA | + | + | − | + | + | + | + | + | + | |
| Other findings | Diabetes mellitus, failure of the pituitary gland | Failure of the pituitary gland, Infertility, Heart failure, Cerebral infarction, Renal infarction | Fetal edema | Fetal edema | Diabetes mellitus | Extramedullary hematopoiesis | Diabetes mellitus | |||||||||
| RBC morphology | ||||||||||||||||
| Target cell | + | + | + | − | + | NA | NA | + | + | + | + | + | + | + | + | |
| Stomatocyte | + | + | + | − | + | NA | NA | + | + | + | + | + | + | + | − | |
| Acanthocyte | − | + | − | + | − | NA | NA | − | − | − | − | − | − | + | − | |
| Elliptocyte | − | − | − | − | − | NA | NA | − | + | − | − | − | − | − | + | |
| Poikilocyte | − | − | − | − | − | NA | NA | − | − | − | − | − | − | − | + | |
| Schistocyte | − | − | + | − | − | NA | NA | − | − | + | − | − | − | − | − | |
| Anisocyte | − | − | − | + | + | NA | NA | − | − | − | + | + | − | − | − | |
| Polychromasia | − | − | − | + | − | NA | NA | − | − | − | − | − | − | − | − | |
| Nucleated erythrocyte | − | + | − | − | − | NA | NA | − | − | − | − | − | − | − | − | |
| Laboratory findings | ||||||||||||||||
| Hb (g/dL) | [13 < : male, 12 < : female] | 12.3 | 8.4 | 10.0 | 10.5 | 14.6 | 12.7 | 6.9 | 13.5 | 15.6 | 11.0 | 10.1 | 9.7 | 8.5 | 10.7 | 10.1 |
| MCV (fL) | [86–98] | 112.3 | 115.6 | 88.0 | 85.0 | 93.3 | 91.7 | 90.8 | 107.1 | 92.7 | 103.6 | 107.4 | 107.1 | 108.3 | 95.3 | 86.6 |
| MCHC (%) | [31–35] | 34.6 | 34.4 | 36.0 | 34.9 | 37.6 | 37.0 | 39.0 | 35.8 | 36.0 | 38.2 | 34.8 | 33.0 | 34.4 | 37.7 | 35.6 |
| Reticulocytes (‰) | [0.2–2.7] | 10.4 | 12.6 | 8.4 | 2.5 | 8.3 | 12.7 | 8.5 | 7.1 | 13.8 | 6.7 | 11.5 | 8.0 | 16.7 | 23.9 | 6.4 |
| LDH (U/L) | [240–490] | 186 | 284 | 236 | 308 | 202 | 173 | 187 | 157 | 144 | 142 | 175 | 139 | 156 | 191 | 239 |
| Haptoglobin (mg/dL) | [19–170] | 97.5 | 3.0 | NA | NA | 86.0 | NA | NA | 16.0 | 56.0 | 13.0 | 2.0 | 18.0 | <10 | NA | <10 |
| Total bilirubin (mg/dL) | [0.2–1.2] | 1.7 | 37.9 | 0.5 | 0.6 | 2.1 | 1.8 | 1.4 | 3.4 | 1.3 | 6.9 | 7.3 | 2.9 | 6.6 | 6.5 | 5.3 |
| Indirect Bilirubin (mg/dL) | [0.2–1.0] | 1.3 | 15.7 | 0.2 | NA | 1.8 | 1.2 | 0.5 | 2.6 | 0.9 | 6.7 | 6.8 | 2.8 | 5.4 | 6.3 | 4.8 |
| Ferritin | [20–250: male, 10–80: female] | 1612 | 2537.3 | 277.3 | NA | 3895 | 172 | 489 | 649.5 | 108.7 | 305.1 | 1663 | NA | 2583.0 | NA | 87.1 |
| Membrane examination | ||||||||||||||||
| AGLT | [30 min < ] | NA | NA | NA | NA | NA | NA | NA | 30 min< | 30 min< | NA | NA | NA | NA | 30 min< | 30 min< |
| EMA (% of control) | 114 | NA | NA | 89 | 103 | NA | NA | 113 | 97 | 112 | 111 | 113 | 112 | 99 | 93 | |
| FCM-OF (% of control) | 193 | NA | NA | 219 | 122 | NA | NA | 132 | 143 | 112 | 113 | 186 | 179 | 142 | 125 | |
| Identified variants | ||||||||||||||||
| Genes | PIEZO1 | PIEZO1 | PIEZO1 | PIEZO1 | PIEZO1 | PIEZO1 | PIEZO1 | PIEZO1 | PIEZO1 | PIEZO1 | PIEZO1 | PIEZO1 | PIEZO1 | KCNN4 | KCNN4 | |
| RefSeq ID | NM_001142864.3 | NM_001142864.3 | NM_001142864.3 | NM_001142864.3 | NM_001142864.3 | NM_001142864.3 | NM_001142864.3 | NM_001142864.3 | NM_001142864.3 | NM_001142864.3 | NM_001142864.3 | NM_001142864.3 | NM_001142864.3 | NM_002250.2 | NM_002250.2 | |
| Affected exons | Exon 11 | Exon 14 | Exon 14 | Exon 32 | Exon 42 | Exon 42 | Exon 42 | Exon 48 | Exon 51 | Exon 51 | Exon 51 | Exon 51 | Exon 51 | Exon 5 | Exon 7 | |
| cDNA change | c.1281_1282ins[GG;1257_1281] | c.1792G > A | c.1792G > A | c.4370 C > T | c.6041 C > T | c.6041 C > T | c.6041 C > T | c.6968 A > C | c.7463 G > A | c.7483_7488dup | c.7483_7488dup | c.7483_7488dup | c.7483_7488dup | c.835 G > A | c.1055 G > A | |
| Protein change | p.A427_L428insGMDQSYVCA | p.V598M | p.V598M | p.A1457V | p.T2014I | p.T2014I | p.T2014I | p.K2323T | p.R2488Q | p.L2495_E2496dup | p.L2495_E2496dup | p.L2495_E2496dup | p.L2495_E2496dup | p.A279T | p.R352H | |
| Type | Insertion | Missense | Missense | Missense | Missense | Missense | Missense | Missense | Missense | Duplication | Duplication | Duplication | Duplication | Missense | Missense | |
| Status | Hetero | Hetero | Hetero | Hetero | Hetero | Hetero | Hetero | Hetero | Hetero | Hetero | Hetero | Hetero | Hetero | Hetero | Hetero | |
| dbSNP ID | − | − | − | rs532444891 | − | − | − | − | rs749288233 | rs1064793545 | rs1064793546 | rs1064793547 | rs1064793548 | − | rs774455945 | |
| SIFT (score) | NA | 0.004 | 0.004 | 0.019 | 0.017 | 0.017 | 0.017 | 0.083 | 0 | NA | NA | NA | NA | 0.237 | 0 | |
| Polyphen2 (score) | NA | 1 | 1 | 0.06 | 0.047 | 0.047 | 0.047 | 0.43 | 0.999 | NA | NA | NA | NA | 0.999 | 0.999 | |
| CADD_phred | NA | 31 | 31 | 24.3 | 28.6 | 28.6 | 28.6 | 26.7 | 35 | NA | NA | NA | NA | 26 | 35 | |
| Clinvar | Not reported | Pathogenic/Likely pathogenic | Pathogenic/Likely pathogenic | Not reported | Not reported | Not reported | Not reported | Not reported | Not reported | Not reported | Not reported | Not reported | Not reported | Not reported | Pathogenic | |
| ACMG criteria | PM2, PM4, PM6, PP4 | PS1, PS3, PM2, PP3, PP4 | PS1, PS3, PM2, PP3, PP4 | PM2, PM6, PP3, PP4 | PS4, PM2, PP3, PP4 | PS4, PM2, PP3, PP4 | PS4, PM2, PP3, PP4 | PS4, PM2, PP3, PP4 | PS1,PS3, PM2, PP1, PP3, PP4 | PS1, PM2, PM4, PP1, PP3, PP4 | PS1, PM2, PM4, PP1, PP3, PP4 | PS1, PM2, PM4, PP1, PP3, PP4 | PS1, PM2, PM4, PP1, PP3, PP4 | PS1, PM5, PP2, PP3, PP4 | PS1, PS3, PM6, PP3, PP4 | |
| Interpretation | Likely pathogenic | Pathogenic | Pathogenic | Likely pathogenic | Likely pathogenic | Likely pathogenic | Likely pathogenic | Likely pathogenic | Pathogenic | Pathogenic | Pathogenic | Pathogenic | Pathogenic | Likely pathogenic | Pathogenic | |
| Reported/novel | Novel | Reported | Reported | Novel | Reported | Reported | Reported | Novel | Reported | Reported | Reported | Reported | Reported | Novel | Reported | |
| Status of other polymorphic variants | ||||||||||||||||
| αLELY variants (c.5572 C > G) | − | Hetero | Homo | Hetero | − | NA | NA | − | − | − | Homo | Hetero | − | Hetero | − | |
| αLELY variants (c.6531–12 C > T) | − | Hetero | Homo | Hetero | − | NA | NA | − | − | − | Homo | Hetero | − | Hetero | − | |
| UGT1A1 variants (*6) | − | − | − | − | − | NA | NA | − | − | − | − | Hetero | − | − | − | |
| UGT1A1 variants (*28) | − | − | − | Hetero | − | NA | NA | − | − | − | − | − | Hetero | − | Homo | |
| Memphis I (SLC4A1: c.166 A > G) | − | − | − | − | − | NA | NA | Hetero | Homo | Hetero | − | − | Hetero | − | − | |
| Memphis II (SLC4A1: c.2561 C > T) | − | − | − | − | − | NA | NA | − | Hetero | − | − | − | − | − | Hetero | |
Pt patient, F female, M male, y years, m months, NA not available, [ ] normal range, _ underbar indicates abnormal finding.