Clinical characteristics of SAMD9L mutation carriers
| Individual . | Germ line SAMD9L mutations . | Revertant SAMD9L mutations . | Hb* (g/L) . | MCV* (fL) . | Plt* (×109/L) . | WBC* (×109/L) . | Cytopenia . | Immunodeficiency . | Myelodysplasia . | Neurology . | Current age (y) . |
|---|---|---|---|---|---|---|---|---|---|---|---|
| F1:I-2 | c.2956C>T | UPD(7q) | 144-147 (0/3) | NA | 126-130 (3/3) | 2.8-3.3 (3/3) | Neutropenia and thrombocytopenia at 61 y of age | No frequent or unusual infections | — | Nystagmus, mild balance impairment, lower limb hyperreflexia | 64 |
| [134-170] | [145-348] | [3.5-8.8] | |||||||||
| F1:I-3† | c.2956C>T | — | 92-125 (9/9) | 95 (0/1) | 100-151 (8/9) | 2.4-3.3 (9/9) | B, NK, and monocytopenia at 54 y of age | Recurrent bacterial infections requiring hospitalization | MDS with der(1;7)(q10;p10) at 56 y of age; bone marrow with prominent erythropoiesis and dysplastic features in megakaryocytopoiesis followed by MDS without elevated blast levels but with increased numbers of T cells | Very mild impairment of balance | 58† |
| [134-170] | [82-98] | [145-348] | [3.5-8.8] | ||||||||
| F1:II-1 | c.2956C>T, c.689C>A | — | 129-139 (0/2) | NA | 246-254 (0/2) | 7.1-7.2 (0/2) | — | — | — | — | 38 |
| [117-153] | [165-387] | [3.5-8.8] | |||||||||
| F1:II-2 | c.2956C>T, c.689C>A | — | 137-138 (0/3) | 91 (0/1) | 176-181 (0/3) | 5.1-6.5 (0/3) | — | — | — | Nystagmus, very mild balance impairment | 33 |
| [117-153] | [82-98] | [165-387] | [3.5-8.8] | ||||||||
| F1:II-4 | c.2956C>T | UPD(7q), c.2957G>T, c.1204_1208del | 130-132 (0/2) | NA | 138-152 (2/2) | 3.1-3.4 (2/2) | Trilineage cytopenia from 18 mo to 3 y of age | — | — | — | 28 |
| [117-153] | [165-387] | [3.5-8.8] | |||||||||
| F1:III-1 | c.2956C>T | — | 102-139 (0/9) | 89-95 (6/6) | 87-128 (8/9) | 2.4-4.5 (9/9) | Thrombocytopenia followed by trilineage cytopenia at 5 mo of age | Congenital CMV infection, hypogammaglobulinemia | MDS with −7 and −22 at 4 y of age; severely hypoplastic bone marrow diagnosed as pediatric refractory cytopenia | Nystagmus, unsteady gait, lower limb stiffness and weakness (after HSCT) | 6 |
| [100-150] | [75-87] | [125-140] | [5-15] | ||||||||
| F1:III-2 | c.2956C>T | UPD(7q) | 113-129 (0/4) | 85-86 (0/3) | 34-246 (1/4) | 5.7-9.0 (1/4) | Transient episode of thrombocytopenia at 21 mo of age | — | — | — | 4 |
| [100-150] | [75-87] | [125-340] | [6-16] | ||||||||
| F2:I-2 | c.2672T>C | c.2302A>T | 107-140 (7/16) | 83-89 (0/16) | 134-255 (2/16) | 3.9-7.6 (0/16) | — | Recurrent otitis in childhood, recurrent sinusitis | — | Nystagmus, memory problems, muscle weakness, cerebellar atrophy | 34 |
| [117-122] | [82-98] | [150-360] | [3.4-8.2] | ||||||||
| F2:II-1 | c.2672T>C | UPD(7q) | 56-149 (29/54) | 72-95 (23/54) | 5-335 (38/54) | 1.4-19.1 (35/54) | Transient episode of severe aplastic anemia at 14 mo of age, after use of chloramphenicol (ear drops) | Recurrent otitis from 4 mo of age | Bone marrow biopsy showed markedly hypoplastic bone marrow; cellularity was assessed to be 5% of normal | ADHD, intermittent vertigo | 13 |
| [117-122] | [82-98] | [150-360] | [3.4-8.2] | ||||||||
| F2:II-4 | c.2672T>C | UPD(7q) | 82-128 (28/90) | 73-90 (15/90) | 37-444 (32/90) | 2.5-12.3 (61/90) | Thrombocytopenia at 2 mo followed by trilineage cytopenia at 14 mo of age | Bronchiolitis at 6 wk and varicella infection at 4 mo of age, both requiring hospitalization; recurrent otitis and laryngitis before the HSCT | MDS −7 at 18 mo of age; normal bone marrow cellularity and dysplastic megakaryocytes and clear myelodysplasia in the megakaryopoiesis | Nystagmus, balance problems, dysmetria, lower limb stiffness, ADHD | 9 |
| [117-122] | [82-98] | [150-360] | [3.4-8.2] |
| Individual . | Germ line SAMD9L mutations . | Revertant SAMD9L mutations . | Hb* (g/L) . | MCV* (fL) . | Plt* (×109/L) . | WBC* (×109/L) . | Cytopenia . | Immunodeficiency . | Myelodysplasia . | Neurology . | Current age (y) . |
|---|---|---|---|---|---|---|---|---|---|---|---|
| F1:I-2 | c.2956C>T | UPD(7q) | 144-147 (0/3) | NA | 126-130 (3/3) | 2.8-3.3 (3/3) | Neutropenia and thrombocytopenia at 61 y of age | No frequent or unusual infections | — | Nystagmus, mild balance impairment, lower limb hyperreflexia | 64 |
| [134-170] | [145-348] | [3.5-8.8] | |||||||||
| F1:I-3† | c.2956C>T | — | 92-125 (9/9) | 95 (0/1) | 100-151 (8/9) | 2.4-3.3 (9/9) | B, NK, and monocytopenia at 54 y of age | Recurrent bacterial infections requiring hospitalization | MDS with der(1;7)(q10;p10) at 56 y of age; bone marrow with prominent erythropoiesis and dysplastic features in megakaryocytopoiesis followed by MDS without elevated blast levels but with increased numbers of T cells | Very mild impairment of balance | 58† |
| [134-170] | [82-98] | [145-348] | [3.5-8.8] | ||||||||
| F1:II-1 | c.2956C>T, c.689C>A | — | 129-139 (0/2) | NA | 246-254 (0/2) | 7.1-7.2 (0/2) | — | — | — | — | 38 |
| [117-153] | [165-387] | [3.5-8.8] | |||||||||
| F1:II-2 | c.2956C>T, c.689C>A | — | 137-138 (0/3) | 91 (0/1) | 176-181 (0/3) | 5.1-6.5 (0/3) | — | — | — | Nystagmus, very mild balance impairment | 33 |
| [117-153] | [82-98] | [165-387] | [3.5-8.8] | ||||||||
| F1:II-4 | c.2956C>T | UPD(7q), c.2957G>T, c.1204_1208del | 130-132 (0/2) | NA | 138-152 (2/2) | 3.1-3.4 (2/2) | Trilineage cytopenia from 18 mo to 3 y of age | — | — | — | 28 |
| [117-153] | [165-387] | [3.5-8.8] | |||||||||
| F1:III-1 | c.2956C>T | — | 102-139 (0/9) | 89-95 (6/6) | 87-128 (8/9) | 2.4-4.5 (9/9) | Thrombocytopenia followed by trilineage cytopenia at 5 mo of age | Congenital CMV infection, hypogammaglobulinemia | MDS with −7 and −22 at 4 y of age; severely hypoplastic bone marrow diagnosed as pediatric refractory cytopenia | Nystagmus, unsteady gait, lower limb stiffness and weakness (after HSCT) | 6 |
| [100-150] | [75-87] | [125-140] | [5-15] | ||||||||
| F1:III-2 | c.2956C>T | UPD(7q) | 113-129 (0/4) | 85-86 (0/3) | 34-246 (1/4) | 5.7-9.0 (1/4) | Transient episode of thrombocytopenia at 21 mo of age | — | — | — | 4 |
| [100-150] | [75-87] | [125-340] | [6-16] | ||||||||
| F2:I-2 | c.2672T>C | c.2302A>T | 107-140 (7/16) | 83-89 (0/16) | 134-255 (2/16) | 3.9-7.6 (0/16) | — | Recurrent otitis in childhood, recurrent sinusitis | — | Nystagmus, memory problems, muscle weakness, cerebellar atrophy | 34 |
| [117-122] | [82-98] | [150-360] | [3.4-8.2] | ||||||||
| F2:II-1 | c.2672T>C | UPD(7q) | 56-149 (29/54) | 72-95 (23/54) | 5-335 (38/54) | 1.4-19.1 (35/54) | Transient episode of severe aplastic anemia at 14 mo of age, after use of chloramphenicol (ear drops) | Recurrent otitis from 4 mo of age | Bone marrow biopsy showed markedly hypoplastic bone marrow; cellularity was assessed to be 5% of normal | ADHD, intermittent vertigo | 13 |
| [117-122] | [82-98] | [150-360] | [3.4-8.2] | ||||||||
| F2:II-4 | c.2672T>C | UPD(7q) | 82-128 (28/90) | 73-90 (15/90) | 37-444 (32/90) | 2.5-12.3 (61/90) | Thrombocytopenia at 2 mo followed by trilineage cytopenia at 14 mo of age | Bronchiolitis at 6 wk and varicella infection at 4 mo of age, both requiring hospitalization; recurrent otitis and laryngitis before the HSCT | MDS −7 at 18 mo of age; normal bone marrow cellularity and dysplastic megakaryocytes and clear myelodysplasia in the megakaryopoiesis | Nystagmus, balance problems, dysmetria, lower limb stiffness, ADHD | 9 |
| [117-122] | [82-98] | [150-360] | [3.4-8.2] |
ADHD, attention deficit hyperactivity disorder; CMV, cytomegalovirus; Hb, hemoglobin; HSCT, hematopoietic stem cell transplantation; MCV, mean corpuscular volume; MDS, myelodysplastic syndrome; NA, not available; Plt, platelets; WBC, white blood cell.
For blood counts, a range of values obtained from each individual is reported. The number of abnormal measurements of the number of total measurements is reported in parentheses. Reference values are reported within square brackets.
Deceased.