HSPA9 CSA patient and family characteristics
| Demographics . | Hematologic phenotype . | HSPA9 and phased rs10117 genotypes . | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ID . | Origin . | Age (y) . | Sex . | Apparent mode of inheritance . | Affected status . | Transfused . | Hb (g/dL) . | MCV (fl) . | RDW (%) . | Protein allele 1 . | Protein allele 2 . | cDNA allele 1 . | cDNA allele 2 . |
| A-I-1 | White (Netherlands) | NA | F | Dominant | Yes | No | NA | NA | NA | p.I137* | p.L645 = | c.[409_410del; 1933C] | c.1933T |
| A-I-2 | White (Netherlands) | NA | F | Dominant | Yes | No | NA | NA | NA | p.I137* | p.L645? | c.[409_410del; 1933C] | c.1933? |
| A-II-1 | White (Netherlands) | 74 | M | Dominant | No | No | 13.4 | 84 | 13.6 | p.L645 = | p.L645 = | c.1933T | c.1933T |
| A-II-2 | White (Netherlands) | 72 | M | Dominant | Yes | No | 13.4 | 85 | 17.0 | p.I137* | p.L645 = | c.[409_410del; 1933C] | c.1933C |
| A-II-3 | White (Netherlands) | 62 | M | Dominant | Yes | No | 12.7 | 87 | 20.1 | p.I137* | p.L645 = | c.[409_410del; 1933C] | c.1933T |
| A-II-4 | White (Netherlands) | 58 | M | Dominant | Yes | No | 12.1 | 82 | 23.1 | p.I137* | p.L645 = | c.[409_410del; 1933C] | c.1933T |
| A-II-5 | White (Netherlands) | 66 | M | Dominant | Yes | No | 13.8 | 81 | 16.8 | p.I137* | p.L645 = | c.[409_410del; 1933C] | c.1933T |
| A-III-1 | White (Netherlands) | 51 | F | Dominant | No | No | 12.7 | 84 | 13.7 | p.L645 = | p.L645 = | c.1933C | c.1933T |
| A-III-2 | White (Netherlands) | 46 | F | Dominant | No | No | 13.2 | 88 | 12.9 | p.L645 = | p.L645 = | c.1933C | c.1933C |
| A-III-3 | White (Netherlands) | 44 | M | Dominant | Yes | No | 14.2 | 85 | 19.5 | p.I137* | p.L645 = | c.[409_410del; 1933C] | c.1933T |
| A-III-4 | White (Netherlands) | 39 | M | Dominant | Yes | No | 16.3 | 84 | 14.8 | p.I137* | p.L645 = | c.[409_410del; 1933C] | c.1933T |
| A-III-5 | White (Netherlands) | 37 | F | Dominant | No | No | 13.7 | 85 | 13.2 | p.L645 = | p.L645 = | c.1933T | c.1933T |
| A-IV-1 | White (Netherlands) | 28 | F | Dominant | No | No | 12.4 | 83 | 12.1 | p.L645 = | p.L645 = | c.1933C | c.1933C |
| A-IV-2 | White (Netherlands) | 24 | M | Dominant | No | No | 17.1 | 85 | 12.3 | p.L645 = | p.L645 = | c.1933C | c.1933C |
| A-IV-3 | White (Netherlands) | 22 | F | Dominant | No | No | 11.6 | 83 | 12.6 | p.L645 = | p.L645 = | c.1933C | c.1933T |
| B-I-1 | White (US) | 57 | F | Dominant | No | No | 14 | 90 | 13.8 | p.L645 = | p.L645 = | c.1933T | c.1933T |
| B-I-2 | White (US) | 53 | M | Dominant | Yes | No | 12.9 | 83 | 21.6 | p.I458_N459del | p.L645 = | c.[1373_1378del; 1933T] | c.1933T |
| B-II-1 | White (US) | 24 | F | Dominant | Yes | No | 8.0 | 77 | 30.5 | p.I458_N459del | p.L645 = | c.[1373_1378del; 1933T] | c.1933T |
| B-II-2 | White (US) | 22 | F | Dominant | No | No | 13.1 | 91 | 13.6 | p.L645 = | p.L645 = | c.1933T | c.1933T |
| B-II-3 | White (US) | 19 | F | Dominant | No | No | 12.9 | 84 | 14.7 | p.L645 = | p.L645 = | c.1933T | c.1933T |
| B-II-4 | White (US) | 15 | M | Dominant | Yes | No | 8.7 | 77 | 31 | p.I458_N459del | p.L645 = | c.[1373_1378del; 1933T] | c.1933T |
| C-I-1 | White (US) | 29 | F | ? Recessive | No | No | 12.1 | 93 | 13.3 | p.R573W | p.L645 = | c.[1717C>T; 1933C] | c.1933T |
| C-I-2 | White (US) | 34 | M | ? Recessive | No | No | 14.1 | 93 | 12.9 | p.L645 = | p.L645 = | c.1933C | c.1933C |
| C-II-1 | White (US) | 1 | F | ? Recessive | Yes | Yes | 6.7 | 83 | 19.3 | p.R573W | L645 = | c.[1717C>T; 1933C] | c.1933C |
| D-II-1 | White (Germany) | 3 mo | F | Recessive | Yes | Yes | 5.8 | 78 | NA | p.S200L | p.V296* | c.[599C>T; 1933?] | c.[883_884del; 1933?] |
| D-II-2 | White (Germany) | 3 wk | F | Recessive | Yes | Yes | 5.6 | 76 | NA | NA | NA | NA | NA |
| K-I-1 | White (Sweden) | 77 | F | Recessive | No | No | 12.6 | 80 | 16.8 | pC487Sfs*3 | p.L645 = | c.[1456_1457del; 1933T] | c.1933C |
| K-II-1 | White (Sweden) | 36 | M | Recessive | Yes | No | 12.5 | 77 | 25.2 | pC487Sfs*3 | p.E577K | c.[1456_1457del; 1933T] | c.[1729G>A; 1933C] |
| K-II-2 | White (Sweden) | 58 | F | Recessive | No | No | 14.1 | 84 | 12.4 | p.E577K | p.L645 = | c.[1729G>A; 1933C] | c.1933C |
| L-I-1 | White (Denmark) | 28 | F | Recessive | No | No | 12.6 | 85 | 14.2 | p.V296* | p.L645 = | c.[883_884del; 1933C] | c.1933T |
| L-I-2 | White (Denmark) | 32 | M | Recessive | No | No | 16.1 | 99 | 13.3 | ?p.203_204ins3 | p.L645 = | c.[609+10A>G;1933T] | c.1933C |
| L-II-1 | White (Denmark) | 4 | F | Recessive | No | No | 13 | 90 | 12.9 | p.L645 = | p.L645 = | c.1933C | c.1933T |
| L-II-2 | White (Denmark) | 3 | F | Recessive | Yes | Yes | 7.2 | 88 | 20.8 | p.V296* | ?p.203_204ins3. | c.[883_884del; 1933C]] | c.[609+10A>G;1933T] |
| M-I-1 | White (French Canadian) | 30 | F | De novo | No | No | 12.6 | 84 | 11.7 | p.L645 = | p.L645 = | c.1933T | c.1933T |
| M-I-2 | White Hispanic (US) | 31 | M | De novo | No | No | 16.3 | 91 | 12.9 | p.L645 = | p.L645 = | c.1933C | c.1933T |
| M-II-1 | White Hispanic/ French Canadian (US) | 5 mo | F | De novo | Yes | Yes | 8.9 | 98 | 22.7 | p.E415K | p.L645 = | c.[1243G>A; 1933C] | c.1933T |
| AM | White (UK) | 20 | F | Unknown | Yes | No | 10.3 | 69 | 32.4 | p.V296* | p.L645 = | c.883_884del | c.1933T |
| N | White (US) | 45 | M | Unknown | Yes | No | 7 | 68 | 38.2 | p.T539K | p.[?;L645 = ] | c.1616C>A | c.[872_879+9dup;1933T]@ |
| V | Asian (Vietnam) | 14 | F | Unknown | Yes | No | 8.9 | 86 | 16.4 | p.S212P | p.L645 = | c.634T>C | c.1933T |
| X | African American (US) | 12 | M | Unknown | Yes | No | 7.4 | 83 | 12.6 | p.G388S | p.L645 = | c.1162G>A | c.1933T |
| Demographics . | Hematologic phenotype . | HSPA9 and phased rs10117 genotypes . | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ID . | Origin . | Age (y) . | Sex . | Apparent mode of inheritance . | Affected status . | Transfused . | Hb (g/dL) . | MCV (fl) . | RDW (%) . | Protein allele 1 . | Protein allele 2 . | cDNA allele 1 . | cDNA allele 2 . |
| A-I-1 | White (Netherlands) | NA | F | Dominant | Yes | No | NA | NA | NA | p.I137* | p.L645 = | c.[409_410del; 1933C] | c.1933T |
| A-I-2 | White (Netherlands) | NA | F | Dominant | Yes | No | NA | NA | NA | p.I137* | p.L645? | c.[409_410del; 1933C] | c.1933? |
| A-II-1 | White (Netherlands) | 74 | M | Dominant | No | No | 13.4 | 84 | 13.6 | p.L645 = | p.L645 = | c.1933T | c.1933T |
| A-II-2 | White (Netherlands) | 72 | M | Dominant | Yes | No | 13.4 | 85 | 17.0 | p.I137* | p.L645 = | c.[409_410del; 1933C] | c.1933C |
| A-II-3 | White (Netherlands) | 62 | M | Dominant | Yes | No | 12.7 | 87 | 20.1 | p.I137* | p.L645 = | c.[409_410del; 1933C] | c.1933T |
| A-II-4 | White (Netherlands) | 58 | M | Dominant | Yes | No | 12.1 | 82 | 23.1 | p.I137* | p.L645 = | c.[409_410del; 1933C] | c.1933T |
| A-II-5 | White (Netherlands) | 66 | M | Dominant | Yes | No | 13.8 | 81 | 16.8 | p.I137* | p.L645 = | c.[409_410del; 1933C] | c.1933T |
| A-III-1 | White (Netherlands) | 51 | F | Dominant | No | No | 12.7 | 84 | 13.7 | p.L645 = | p.L645 = | c.1933C | c.1933T |
| A-III-2 | White (Netherlands) | 46 | F | Dominant | No | No | 13.2 | 88 | 12.9 | p.L645 = | p.L645 = | c.1933C | c.1933C |
| A-III-3 | White (Netherlands) | 44 | M | Dominant | Yes | No | 14.2 | 85 | 19.5 | p.I137* | p.L645 = | c.[409_410del; 1933C] | c.1933T |
| A-III-4 | White (Netherlands) | 39 | M | Dominant | Yes | No | 16.3 | 84 | 14.8 | p.I137* | p.L645 = | c.[409_410del; 1933C] | c.1933T |
| A-III-5 | White (Netherlands) | 37 | F | Dominant | No | No | 13.7 | 85 | 13.2 | p.L645 = | p.L645 = | c.1933T | c.1933T |
| A-IV-1 | White (Netherlands) | 28 | F | Dominant | No | No | 12.4 | 83 | 12.1 | p.L645 = | p.L645 = | c.1933C | c.1933C |
| A-IV-2 | White (Netherlands) | 24 | M | Dominant | No | No | 17.1 | 85 | 12.3 | p.L645 = | p.L645 = | c.1933C | c.1933C |
| A-IV-3 | White (Netherlands) | 22 | F | Dominant | No | No | 11.6 | 83 | 12.6 | p.L645 = | p.L645 = | c.1933C | c.1933T |
| B-I-1 | White (US) | 57 | F | Dominant | No | No | 14 | 90 | 13.8 | p.L645 = | p.L645 = | c.1933T | c.1933T |
| B-I-2 | White (US) | 53 | M | Dominant | Yes | No | 12.9 | 83 | 21.6 | p.I458_N459del | p.L645 = | c.[1373_1378del; 1933T] | c.1933T |
| B-II-1 | White (US) | 24 | F | Dominant | Yes | No | 8.0 | 77 | 30.5 | p.I458_N459del | p.L645 = | c.[1373_1378del; 1933T] | c.1933T |
| B-II-2 | White (US) | 22 | F | Dominant | No | No | 13.1 | 91 | 13.6 | p.L645 = | p.L645 = | c.1933T | c.1933T |
| B-II-3 | White (US) | 19 | F | Dominant | No | No | 12.9 | 84 | 14.7 | p.L645 = | p.L645 = | c.1933T | c.1933T |
| B-II-4 | White (US) | 15 | M | Dominant | Yes | No | 8.7 | 77 | 31 | p.I458_N459del | p.L645 = | c.[1373_1378del; 1933T] | c.1933T |
| C-I-1 | White (US) | 29 | F | ? Recessive | No | No | 12.1 | 93 | 13.3 | p.R573W | p.L645 = | c.[1717C>T; 1933C] | c.1933T |
| C-I-2 | White (US) | 34 | M | ? Recessive | No | No | 14.1 | 93 | 12.9 | p.L645 = | p.L645 = | c.1933C | c.1933C |
| C-II-1 | White (US) | 1 | F | ? Recessive | Yes | Yes | 6.7 | 83 | 19.3 | p.R573W | L645 = | c.[1717C>T; 1933C] | c.1933C |
| D-II-1 | White (Germany) | 3 mo | F | Recessive | Yes | Yes | 5.8 | 78 | NA | p.S200L | p.V296* | c.[599C>T; 1933?] | c.[883_884del; 1933?] |
| D-II-2 | White (Germany) | 3 wk | F | Recessive | Yes | Yes | 5.6 | 76 | NA | NA | NA | NA | NA |
| K-I-1 | White (Sweden) | 77 | F | Recessive | No | No | 12.6 | 80 | 16.8 | pC487Sfs*3 | p.L645 = | c.[1456_1457del; 1933T] | c.1933C |
| K-II-1 | White (Sweden) | 36 | M | Recessive | Yes | No | 12.5 | 77 | 25.2 | pC487Sfs*3 | p.E577K | c.[1456_1457del; 1933T] | c.[1729G>A; 1933C] |
| K-II-2 | White (Sweden) | 58 | F | Recessive | No | No | 14.1 | 84 | 12.4 | p.E577K | p.L645 = | c.[1729G>A; 1933C] | c.1933C |
| L-I-1 | White (Denmark) | 28 | F | Recessive | No | No | 12.6 | 85 | 14.2 | p.V296* | p.L645 = | c.[883_884del; 1933C] | c.1933T |
| L-I-2 | White (Denmark) | 32 | M | Recessive | No | No | 16.1 | 99 | 13.3 | ?p.203_204ins3 | p.L645 = | c.[609+10A>G;1933T] | c.1933C |
| L-II-1 | White (Denmark) | 4 | F | Recessive | No | No | 13 | 90 | 12.9 | p.L645 = | p.L645 = | c.1933C | c.1933T |
| L-II-2 | White (Denmark) | 3 | F | Recessive | Yes | Yes | 7.2 | 88 | 20.8 | p.V296* | ?p.203_204ins3. | c.[883_884del; 1933C]] | c.[609+10A>G;1933T] |
| M-I-1 | White (French Canadian) | 30 | F | De novo | No | No | 12.6 | 84 | 11.7 | p.L645 = | p.L645 = | c.1933T | c.1933T |
| M-I-2 | White Hispanic (US) | 31 | M | De novo | No | No | 16.3 | 91 | 12.9 | p.L645 = | p.L645 = | c.1933C | c.1933T |
| M-II-1 | White Hispanic/ French Canadian (US) | 5 mo | F | De novo | Yes | Yes | 8.9 | 98 | 22.7 | p.E415K | p.L645 = | c.[1243G>A; 1933C] | c.1933T |
| AM | White (UK) | 20 | F | Unknown | Yes | No | 10.3 | 69 | 32.4 | p.V296* | p.L645 = | c.883_884del | c.1933T |
| N | White (US) | 45 | M | Unknown | Yes | No | 7 | 68 | 38.2 | p.T539K | p.[?;L645 = ] | c.1616C>A | c.[872_879+9dup;1933T]@ |
| V | Asian (Vietnam) | 14 | F | Unknown | Yes | No | 8.9 | 86 | 16.4 | p.S212P | p.L645 = | c.634T>C | c.1933T |
| X | African American (US) | 12 | M | Unknown | Yes | No | 7.4 | 83 | 12.6 | p.G388S | p.L645 = | c.1162G>A | c.1933T |
c.1933 is the site of rs10117. An unphased genotype at this site is indicated as c.1933?, as in patient A-I-2. The genotype of A-I-1 was inferred from her 4 genotyped children. A-I-2 is inferred to be a carrier of the deletion allele segregating in the family based on her affected status and the genotype of her son. A-I-1 and A-I-2 were phenotyped in van Waveren Hogervorst et al.6 #c.609+10A>G is predicted to create a de novo splice donor site 9 bp downstream of exon 6. @c.872_879+9dup allele is predicted to duplicate a splice donor site and adjacent nucleotides, has minor allele frequency of 1.33%, and is present in the homozygous state in the ExAC database. For this reason, it is inferred not to be pathogenic. Patients B-I-2 and B-II-1 also had retinitis pigmentosa. Patient M-II-1 had coexisting neutropenia, thrombocytopenia, and renal calculi.
cDNA, complementary DNA; F, female; Hb, hemoglobin; MCV, mean cell volume; M, male; MAF, minor allele frequency; MCV, mean cell volume; NA, not available; RDW, red blood cell distribution width.