Table 2 Main clinical and neuroimaging features of the NOS3 and GUCY1A3 mutated probands reported in the present study and in literature
Patients | M084* | M035* | M038* | F1** (2 affected siblings) | F2** (2 affected siblings) | F3** (5 affected siblings) | M041*** | M149*** |
|---|---|---|---|---|---|---|---|---|
Mutated gene | NOS3a | NOS3a | GUCY1A3b | GUCY1A3b | GUCY1A3b | GUCY1A3b | GUCY1A3b | GUCY1A3b |
Variant description | HMZ variant | HMZ variant | HMZ variant | HMZ variant | HMZ variant | HMZ variant | Comp. HTZ variant | Comp.HT variant |
c.1502 + 1G > C | c.1942 T > C | c.1778G > A | c.1170delA | c.1045C > T | c.1086 + 1G > A | c.1258C > T AND c.1594G>T | c.334-335delGA AND c.1550G>A | |
p.Ala502Trpfs*71 | p.C648R | p.R593H | p.Glu391Lysfs*19 | p.Arg349* | p.(?) | p.Arg420* AND p.Gly652* | p.Glu112fr AND p.Cys517Tyr | |
Gender | Female | Male | Female | Male/male | Female/female | 4 males/1 female | Male | Female |
Consanguinity | Yes | Yes | Yes | Yes | Yes | Yes | No | No |
Moyamoya angiopathy | Yes | Yes | Yes | Yes (1/2) | Yes (1/2) | Yes (2/5)c | Yes | Yes |
- Anterior circ. involvement | Yes | Yes | Yes | Yes | Yes | Yes (2/5) | Yes | Yes |
- Posterior circ. involvement | Yes | Yes | No | Yes | Yes | Yes (1/5) | Yes | Not reported |
MMA type according the first symptom | TIA | Ischemic stroke | TIA | Ischemic stroke | Ischemic stroke | Ischemic stroke (2/5) | Ischemic stroke | Ischemic stroke |
Age at first MMA symptom | 9m | 6m | 43y | 3y | 7m | 2y/7m | 18y | 20m |
MMA symptoms | ||||||||
- TIA | Yes | No | Yes | No | No | Yes | Yes | No |
- Ischemic stroke | Yes | Yes | Yes | Yes | Yes | Yes | No | Yes |
- Hemorrhagic stroke | No | No | No | No | No | No | No | No |
- Epilepsy | No | No | Yes | No | Yes | No | Yes | No |
Other symptoms | ||||||||
- Arterial hypertension | No | No | Yes | Yes (2/2) | Yes (2/2) | Not reported | Yes | Yes |
- Systemic artery stenosis | No | No | Yes (SMA) | No | No | Not reported | Not reported | No |
- Early-onset achalasia | No | No | No | Yes (2/2) | Yes (2/2) | Yes (5/5) | Yes | No |
- Juvenile glaucoma | Yes | No | No | No | No | Not reported | Not reported | Not reported |
- Raynaud and/or livedo | No | No | No | Yes (1/2) | Yes (1/2) | Not reported | Not reported | Not reported |
- Other symptoms | No | IUGR, psychomotor delay, neonatal hypoglycemia, short stature, facial and extremities dysmorphism, pigmented skin spots and abdominal patches, cryptorchidism | No | Erectile dysfunction (1/2), low platelet count (1/2) | Gastroesophageal reflux, asthma, bilateral inguinal hernia, sudden death | Ascending aorta enlargement | ||