Table 1.
Results of this study.
| Patient 1 | Patient 2 | Patient 3 | Patient 4 | Patient 5 | Patient 6 | Patient 7 | Patient 8 | Patient 9 | Patient 10 | Patient 11 | Patient 12 | Patient 13 | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Subtype | SPH1 | SPH1 | SPH1 | SPH1 | SPH1 | SPH1 | SPH2 | SPH2 | SPH2 | SPH2 | SPH3 | SPH4 | SPH5 |
| Gender | Female | Female | Male | Female | Male | Male | Male | Male | Female | Male | Female | Male | Male |
| Age | 37 y | 71 y | 6 y | 1 y 6 m | 2 m | 15 y | 14 y | 16 y | 13 y | 27 y | 62 y | 45 y | 55 y |
| Family history | – | – | + | – | + | + | + | – | + | – | – | + | – |
| Clinical histories | |||||||||||||
| Splenomegaly | + | + | + | + | – | + | + | + | – | + | – | + | + |
| Splenectomy | – | – | + | – | – | – | + | – | – | + | – | + | – |
| Gallstone | + | + | – | – | – | – | + | – | – | – | + | – | – |
| Blood transfusion | NA | + | + | + | + | – | + | – | – | – | + | – | + |
| Laboratory testing | |||||||||||||
| Hb (g/dL) [13 < : male, 12 < : female] | 11.7 | 7.1 | 13.5 | 7.9 | 8.2 | 12.6 | 15.6 | 11.2 | 11 | 12.9 | 5.9 | 15.6 | 5.1 |
| MCV (fL) [86~98 fL] | 86.8 | 106.1 | 80.2 | 85.2 | 87.6 | 95 | 86.5 | 84.9 | 82 | 88.9 | 106.9 | 96 | 113.2 |
| MCHC (%) [31–35%] | 34.6 | 36.2 | 37 | 31.1 | 34 | 34.8 | 35.3 | 33 | 35.5 | 33.5 | 32.1 | 35.5 | 31.6 |
| Reticurocytes (‰) [0.2–2.7‰] | 92 | 55 | 18.6 | 248 | 26 | 44 | 16.5 | 69 | 17.9 | 30 | 34 | NA | 19.5 |
| LDH (U/L) [240~490 U/L] | 162 | 187 | 200 | 535 | 281 | 272 | 246 | 222 | 246 | 240 | 156 | 157 | 286 |
| Haptoglobin (mg/dL) [19–170 mg/dL] | <10 | <2 | NA | <10 | NA | 2 | 43 | 1 | <10 | 20 | 37 | NA | ≦10 |
| Total Bilirubin (mg/dL) [0.2–1.2 mg/dL] | 3.7 | 9.9 | 0.4 | 1.8 | 2.2 | 3.2 | 1 | 6.5 | 3.8 | 1.5 | 3.4 | 36 | 1.8 |
| Indirect Bilirubin (mg/dL) [0.2–1.0 mg/dL] | 0.6 | 5.1 | 0.1 | 0.8 | 2.1 | 2.7 | 0.6 | 6 | 2.6 | 0.8 | 3.1 | NA | 1 |
| RBC morphology | Anysocyte,spherocyte | Elliputocyte, spherocyte, stomatocyte | Codocyte, spherocyte | Anisocyte, spherocyte | Anisocyte, codocyte, stomatocyte | Anisocyte, codocyte | Spherocyte | Spherocyte | Spherocyte | Spherocyte | Anisocyte, codocyte, stomatocyte | Spherocyte | Anisocyte, erythrocyte, polychromatophilic, stomatocyte |
| Specific examination | |||||||||||||
| AGLT | 150 s | 30 min< | NA | NA | 30 min< | 30 min< | NA | NA | NA | NA | 30 min< | NA | 45sec |
| EMA (% of control) | 72.7 | 93 | 35.8 | 70.1 | 67.7 | 97.3 | 34.8 | 32 | 15.3 | NA | 106.3 | 15.8 | 90.2 |
| FCM-OF(46.0–68.8%) | 23.8 | NA | 10.2 | 7.2 | NA | NA | 14.9 | 17.2 | 4.2 | 13.6 | NA | 1.8 | NA |
| Other findiings | – | – | – | – | – | – | – | – | – | – | – | Spina bifida | Epilepsy, developmental delay, hearing difficulty |
| Variant information | |||||||||||||
| Chromosome | Chr8 | Chr8 | Chr8 | Chr8 | Chr8 | Chr8 | Chr14 | Chr14 | Chr14 | Chr14 | Chr1 | Chr17 | Chr15 |
| Gene | ANK1 | ANK1 | ANK1 | ANK1 | ANK1 | ANK1 | SPTB | SPTB | SPTB | SPTB | SPTA1 | SLC4A1 | EPB42 |
| Genomic cordinate (GRCh37/hg19) | |||||||||||||
| Start | 41655025 | 41584867 | 41584808 | 41584761 | 41580711 | 41575626 | 65259974 | 65249125 | 65246577 | 65239394 | 158632491 | 42334875 | 43507389 |
| End | 41655025 | 41584867 | 41584812 | 41584764 | 41580711 | 41575626 | 65259974 | 65249125 | 65246577 | 65239395 | 158632491 | 42334875 | 43507389 |
| HGVS (Coding) | NM_000037.4 | NM_001142446.2 | NM_000037.4 | NM_000037.4 | NM_000037.4 | NM_000037.4 | NM_001024858.4 | NM_001024858.4 | NM_001024858.4 | NM_001024858.4 | NM_003126.4 | NM_000342.4 | NM_000119 |
| Location | Intron 1 | Intron 4 | Exon 5 | Intron 5 | Exon 9 | exon11 | Exon 13 | Exon 19 | Exon 20 | Exon 25 | Intron 17 | Exon 13 | exon3 |
| cDNA change | c.27 + 5G>C | c.427-1G>T | c.382_386del | c.426 + 4_426 + 7del | c.841C>T | c.1204G>A | c.2407del | c.4149dup | c.4339G>T | c.5456_5457delinsTT | c.2464 + 1 G>A | c.1469G>A | c.424G>A |
| Protein change | p.Lys128Phefs*7 | p.Arg281* | p.Glu402Lys | p.Glu803Serfs*17 | p.Arg1384Alafs*7 | p.Glu1447* | p.Glu1819Val | p.Arg490His | p.Ala142Thr | ||||
| Type | Splicing | Splicing | Frameshift | Splicing | Nonsense | Missense | Frameshift | Frameshift | Nonsense | Missense | Splicing | Missense | Missense |
| Status | Hetero | Hetero | Hetero | Hetero | Hetero | Hetero | Hetero | Hetero | Hetero | Hetero | Homo | Hetero | Homo |
| dbSNP | – | – | – | – | – | rs1350849760 | – | rs778901641 | – | – | rs774632615 | – | rs104894487 |
| Clinvar | – | – | – | – | – | Not reported | – | Not reported | – | – | Likely pathogenic | – | Uncertain significance |
| SIFT (score) | NA | NA | NA | NA | NA | 0.028 | NA | NA | NA | NA | NA | 0 | 0 |
| Polyphen2 (score) | NA | NA | NA | NA | NA | 1 | NA | NA | NA | NA | NA | 1 | 1 |
| CADD_phred | NA | 27.5 | NA | NA | 37 | 34 | NA | NA | 38 | NA | 25 | 29.6 | 29.5 |
| ACMG criteria | PS1,PM2,PM4, PM6,PP3,PP4 | PM2,PM4, PM6,PP4 | PVS1, PM2,PM4 | PM2,PM4, PM6,PP4 | PVS1, PM2,PM4 | PM2, PP3, PP4 | PVS1, PM2, PM4 | PVS1, PM2, PM6, PP4 | PVS1, PM2, PM4 | PM2, PM6, PP4 | PS1, PM2, PM3, PP4 | PM2, PM5, PP3, PP4 | PS1, PM2, PM3, PP3, PP4 |
| Interpretation | Pathogenic | Likely pathogenic | Pathogenic | Likely pathogenic | Likely pathogenic | VUS | Pathogenic | Pathogenic | Pathogenic | VUS | Likely pathogenic | Likely pathogenic | Pathogenic |
| Previous report | Nakanishi et al.12 (Ankyrin Nara II) | Novel | Novel | Novel | van Vuren et al.13 | – | Novel | – | Novel | Novel | – | Novel$ | Bouhassira et al.11(Protein 4.2 NIPPON) |
y years; m months; NA not available; MCV mean corpuscular volume; MCHC mean corpuscular hemoglobin concentration; LDH lactate dehydrogenase; RBC red blood cell; [], standard value; _, underbar indicates abnormal finding; chr chromosome; VUS variant of uncertain significance; $ a similar variant “R490C” was reported by Dhermy et al.10
Some damaging scores could not be calculated because they were splicing or loss-of-function.
In cases of splenectomy, only the data of the patients in the period of post-splenectomy is available.