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 |
| 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.