Table 3.
Comparison of clinical phenotypes and findings in fruit flies expressing PPFIA3 missense variants
|
PPFIA3 variants (GRCh37, hg19) |
c.115C>T (p.Arg39Cys) |
c.943G>T (p.Ala315Ser) |
c.1243C>T (p.Arg415Trp) |
c.1638G>T (p.Trp546Cys) |
c.2350C>T (p.Arg784Trp) |
|||
|---|---|---|---|---|---|---|---|---|
| Individual | 1 | 2 | 7 | 8 | 9 | 12 | 13 | |
| Key clinical phenotypes in individuals with PPFIA3 variants | location | coiled-coil | coiled-coil | coiled-coil | disordered region | disordered region | ||
| abnormal EEG | + | + | N/A | + | + | − | + | |
| epilepsy | + | − | N/A | + | − | − | + | |
| autism/autistic features | − | − | N/A | + | + | + | − | |
| DD/ID | + | + | N/A | + | + | + | + | |
| hypotonia | + | N/A | N/A | + | − | − | − | |
| dysmorphisms | + | + | + | + | N/A | − | − | |
| micro- or macrocephaly | − | − | + | + | N/A | − | − | |
| clinical features (# present/total reported) | 5/7 | 3/6 | 2/2 | 7/7 | 3/5 | 2/7 | 3/7 | |
| Findings in fruit flies expressing PPFIA3 variants | eclosion defect | + | + | + | − | − | − | + |
| abnormal leg morphology | + | + | + | − | − | − | + | |
| climbing defect | + | + | + | − | + | − | + | |
| bang sensitivity | + | + | + | − | − | − | + | |
| NMJ defect | + | N/A | + | − | − | − | + | |
| liprin-α LOF rescue defect | + | N/A | + | − | + | − | + | |
| fly phenotypes (# present/total assays) | 6/6 | 4/4 | 6/6 | 0/6 | 2/6 | 0/6 | 6/6 | |
| variant severity according to the number of phenotypes in fly assays (0: no effect in fly assays; 1–2: mild; 3–4: moderate; 5–6: severe) | severe | at least moderate | severe | no effect | mild | no effect | severe | |
Abbreviations: electroencephalogram (EEG), delayed development (DD), intellectual disability (ID), no information available (n/a), loss of function (LOF), neuromuscular junction (NMJ).