Table 3.
genotype/phenotype correlation in DADA2
| Mutation | Exon | N° of patients | Associated symptoms (% of patients) |
|---|---|---|---|
| M1T | 2 | 1 in heterozygosis | Fever Skin: Non-Langerhans cell histiocytosis CNS/PNS: ischemic stroke Visceral: involvement: hepatomegaly, splenomegaly. portal hypertension, hypertension (100 %) |
| K13del | 2 | 2 in heterozygosis | Fever (50 %) Skin: Livedo racemosa (50 %), skin nodules (50 %) Immune/hematologic system: hypogammaglobulinemia (100 %), recurrent infections (50 %) |
| 28-kb-deletion | 2 | 1 in heterozygosis | Fever Skin: Livedo reticularis, urticarial rash CNS/PNS: ischemic and haemorrhagic strokes Visceral involvement: hepatomegaly, splenomegaly. chronic gastritis Immune/hematologic system: leukopenia, hypogammaglobulinemia (100 %) |
| G47R | 2 | 27 in homozygosis | Fever (64 %) Skin: Livedo reticularis (60 %), skin nodules (35 %), ulcerations at extremities/digital necrosis (32 %), Raynaud’s phenomenon (28 %), purpuric/vasculitic rash (18 %), erythema nodosum (18 %), panniculitis (3 %) CNS/PNS: ischemic stroke (21 %), hemorrhagic stroke (7 %), intracranial haemorrhage (11 %), cranial nerve paralysis (14 %), polineuropathy (11 %), neurosensorial hearing loss (3 %). Visceral involvement: abdominal pain (21 %), intestinal vasculitis (14 %), hepatomegaly (3 %), splenomegaly (7 %), hypertransaminasemia (3 %), hypertension (25 %). Immune/hematologic system: Leucopoenia (3 %), anaemia (3 %), lymphadenopathy (3 %). |
| 1 in heterozygosis | |||
| G47A | 2 | 2 in heterozygosis | Fever (100 %) Skin: Livedo reticularis (100 %), urticarial rash (100 %) CNS/PNS: ischemic and haemorrhagic strokes (100 %) Visceral involvement: hepatomegaly (100 %), splenomegaly (100 %), portal hypertension (100 %) Immune/hematologic system: Pancytopenia (100 %), hypogammaglobulinemia (100 %). |
| G47V | 2 | 1 in heterozygosis | Fever Skin: Livedo reticularis Visceral involvement: hypertension, abdominal and renal aneurysm (100 %). |
| I93T | 2 | 1 in heterozygosis | Fever Skin: Non-Langerhans cell histiocytosis CNS/PNS: ischemic stroke Visceral: involvement: hepatomegaly, splenomegaly. portal hypertension, hypertension (100 %) |
| A109D | 3 | 1 in heterozygosis | Fever Skin: Livedo reticularis CNS/PNS: ischemic stroke Visceral involvement: splenomegaly (100 %). |
| H112Q | 3 | 1 in heterozygosis | Fever Skin: Livedo reticularis, urticarial rash CNS/PNS: ischemic and haemorrhagic strokes Visceral involvement: hepatomegaly, splenomegaly, portal hypertension Immune/hematologic system: Pancytopenia, hypogammaglobulinemia (100 %). |
| T119A | 3 | 4 in heterozygosis | Fever (100 %) Skin: Livedo reticularis, ulceration of extremities (100 %) CNS/PNS: ischemic and haemorrhagic strokes (100 %) |
| G142S | 3 | 4 in heterozygosis | Fever (100 %) Skin: Livedo reticularis, ulceration of extremities (100 %) CNS/PNS: ischemic and haemorrhagic strokes (100 %) |
| R169Q | 3 | 15 in homozygosis | Fever (37 %) Skin: Livedo reticularis (58 %), skin nodules (4 %), ulcerations at extremities/digital necrosis (8 %), Raynaud’s phenomenon (8 %), purpuric/vasculitic rash (13 %), erythema nodosum (13 %), eczema (20 %) CNS/PNS: ischemic stroke (54 %), hemorrhagic stroke (13 %), intracranial haemorrhage (13 %), cranial nerve paralysis (37 %), polineuropathy (8 %), neurosensorial hearing loss (8 %). Visceral involvement: abdominal pain (17 %), bowel ulcerations (8 %), chronic gastritis (4 %), bowel stenosis (4 %), colitis (4 %), hepatomegaly (45 %), splenomegaly (58 %), acute liver failure (4 %), hypertension (8 %). Immune/hematologic system: hypogammaglobulinemia (62 %), pancytopenia (8 %), leucopoenia (20 %), lymphopenia (13 %), granulocytopenia (4 %), anaemia (25 %), thrombocytopenia (4 %), lymphadenopathy (25 %), recurrent infections (29 %). |
| 9 in heterozygosis | |||
| P193L | 4 | 1 in heterozygosis | Fever Skin: Livedo reticularis, ulcerations at extremities CNS/PNS: ischemic stroke, TIA, intracranial haemorrhage, polineuropathy Visceral involvement: bowel stenosis, oral aphtae Immune/hematologic system: hypogammaglobulinemia (100 %). |
| M243R | 4 | 2 in heterozygosis | Fever (50 %) Skin: erythema nodosum (50 %) CNS/PNS: intracranial haemorrhage (50 %) Visceral involvement: splenomegaly (100 %) Immune/hematologic system: hypogammaglobulinemia (100 %), recurrent infections (100 %). |
| P251L | 4 | 4 in heterozygosis | Fever (25 %) Skin: Livedo reticularis (75 %), vasculitic rash (50 %) CNS/PNS: ischemic stroke (75 %), cranial nerve paralysis (100 %), neurosensorial hearing loss (25 %). Visceral involvement: hypertension (25 %), epididymitis (25 %) |
| W264S | 5 | 1 in heterozygosis | Fever Skin: Livedo reticularis Visceral involvement: hypertension, abdominal and renal aneurysm (100 %). |
| R306* | 6 | 1 in heterozygosis | Fever Skin: rash CNS/PNS: ischemic stroke, hemorrhagic stroke, intracranial haemorrhage (100 %) |
| N328K | 7 | 2 in heterozygosis | Fever (50 %) Skin: Livedo racemosa (50 %), skin nodules (50 %) Immune/hematologic system: hypogammaglobulinemia (100 %), recurrent infections (50 %) |
| Y453C | 9 | 3 in heterozygosis | Fever (100 %) Skin: Livedo reticularis (100 %), urticarial rash (33 %) CNS/PNS: ischemic stroke (100 %), haemorrhagic strokes (33 %) Visceral involvement: hepatomegaly (66 %), splenomegaly (100 %), portal hypertension (33 %) Immune/hematologic system: Pancytopenia (66 %), hypogammaglobulinemia (66 %). |