Table 1.
Clinical and molecular characteristics of individuals with SRP54 mutations
| Family | ID | Sex | Age at diagnosis | Age at last follow-up (years) | ANCs (per microliter) before G-CSF therapy | Severe bacterial infections* | Stomatitis gingivitis | Maturation arrest on bone marrow smear (before G-CSF therapy) | G-CSF therapy mean (maximum) dose (µg/kg/day) | Neurological symptoms | Exocrine pancreatic insufficiency† | Other extrahematopoietic symptoms | SRP54 genotype cDNA; protein inheritance |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F1 | P1 | M | 9.8 months | 8 | 270 | Yes | Yes | Yes | Yes/5 (5) | No | No | No | c.337G>C p.Gly113Arg de novo |
| F2 | P2 | M | 4.6 months | 3 | 443 | Yes | No | Yes | Yes/16 (20) | No | Yes | No | c.349_351del p.Thr117del de novo |
| F3 | P3 | F | 1.7 months | 15 | 440 | Yes | Yes | Yes | Yes/4 (5) | No | No | No | c.349_351del p.Thr117del dominant |
| P4 Father | M | 2.1 years | 44 | 100 | No | Yes | Yes | No | No | No | No | ||
| F4 | P5 | M | 10.6 months | 11 (HSCT at 1.5) | 190 | Yes | No | Yes | Yes/refractory till 50 µg/kg | Intellectual disability, autism spectrum disorder‡ | No | No | c.349_351del p.Thr117del nd |
| F5 | P6 | M | 5 years | 32 | 530 | No | Yes | Yes | Yes/16 (20) | No | No | Osteoporosis Type 2 diabetes at 31 years | c.349_351del p.Thr117del de novo§ |
| F6 | P7 | M | 2 days | 10 | 45 | Yes | Yes | Yes | Yes/6 (15) | No | No | No | c.349_351del p.Thr117del de novo |
| F7 | P8 | F | 10.1 months | 15 | 120 | No | Yes | Yes | Yes/10 (10) | No | No | No | c.349_351del p.Thr117del de novo |
| F8 | P9 | M | 1 months | 24 | 250 | Yes | Yes | Yes | Yes/5 (5) | No | No | IUGR, GH deficiency and GH therapy (Final height of 1.69 m) | c.349_351del p.Thr117del nd |
| F9 | P10 | M | 4.2 months | 11 | 230 | Yes | No | Yes | Yes/10 (10) | No | No | No | c.349_351del p.Thr117del de novo |
| F10 | P11‖ | M | 12.7 months | 7 | 360 | Yes | Yes | Yes | Yes/5 (5) | No | No | No | c.349_351del p.Thr117del de novo |
| F11 | P12‖ | M | 1.3 years | 39 | 90 | Yes | Yes | Yes | Yes/2 (5) | No | No | No | c.349_351del p.Thr117del de novo |
| F12 | P13‖ | F | 1 days | 3 | 100 | Yes | N | Yes | Yes/20 (20) | No | No | No | c.349_351del p.Thr117del de novo |
| F13 | P14 | M | 10 days | 6 | 110 | Yes | Yes | Yes | Yes/5 (5) | No | No | No | c.349_351del p.Thr117del dominant |
| P15 | F | 20 years | 28 | 345 | No | Yes | Yes | No | No | No | No | ||
| F14 | P16‖ | F | 4.2 months | 17 | 435 | Yes | No | Yes (intermittent) | Yes/5 (5) | No | No | No | c.353G>A p.Cys118Tyr dominant |
| P17‖ Father | M | 2.8 months | 46 | 960 | Yes | Yes | Yes (intermittent) | Yes/5 (5) | Learning difficulties** | No | No | ||
| P18 Brother | M | 8.3 months | 21 | 1090 | No | No | No | No | Learning difficulties** | No | No | ||
| F15 | P19‖ | F | 24 days | 6 | 215 | Yes | Yes | Yes | Yes/9 (10) | Neurodevelopmental delay | No | No | c.407G>A p.Cys136Tyr de novo |
| F16 | P20 | F | 2.9 months | 32 | 144 | Yes | Yes | Yes | Yes/13 (30) | Neurodevelopmental delay, dysmorphy | No | Short stature (final height of 1.48 m), obesity | c.407G>A p.Cys136Tyr nd |
| F17 | P21 | M | 9 months | 43 | 106 | Yes | Yes | Yes | Yes/5 (5) | Neurodevelopmental delay, extreme delayed speech | Yes (Lipomatosis) | IUGR | c.668C>A p.Ala223Asp de novo |
| F18 | P22 | M | 15 days | 1.5 (HSCT at 0.5) | 220 | Yes | N | Yes | Yes/26 (50) | Neurodevelopmental delay, epilepsy | No) | No | c.677G>A p.Gly226Glu de novo |
| F19 | P23 | M | 1 months | 25.6 | 92 | Yes | Yes | Yes | Yes/14 (30) | Neurodevelopmental delay, extreme delayed speech | Yes (Lipomatosis) | IUGR, short stature (final height of 1.53 m), bone dysplasia | c.821G>A p.Gly274Asp de novo |
ANC, absolute neutrophil count; F, female; GH, growth hormone; HSCT, hematopoietic stem cell transplant; IUGR, intrauterine growth retardation; M, male; nd, not determined.
*
Septicemia, pneumonia, cellulitis, liver abscess, and osteitis were considered as severe infections.
†
Exocrine pancreatic insufficiency requiring pancreatic enzyme therapy.
‡
Father with severe neuropsychiatric disorder.
§
SRP54 mutation identified in the asymptomatic father at a mosaic state (9%; supplemental Figure 1).
‖
Cases analyzed by WES.
**
Learning difficulties defined as requiring attendance at a special school.