Table 5.
Heterozygous damaging rare variants associated with other autosomal recessive inheritance neurodegenerative disorders
| Patient ID | Form | AOO | Sex | Symptoms | Gene | Variant ID | Zygosity | Clinical significance | ACMG classification | MAF (non-neuro) | Inheritance | Patients | Controls | Reference |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P50 | F | 60 | m | Short-term memory impairment; parkinsonism, prefrontal symptoms | C19ORF12 | p.P60A c.178C > G | het | D | LP | - | AR, AD | 1/54 | 0/137 | - |
| P81 | S | 59 | m | Behavioral changes, anxiety | PRKN | p.T240M c.719C > T rs137853054 | het | Conf. Of P | P | < 0.01 | AR | 1/54 | 0/137 | [25] |
| P35 | S | 61 | m | Short-term memory impairment, visuospatial disturbancy, dyscalculia, apraxia | LRRK2 | p.A1862V c.5585C > T | het | D | VUS | - | AD | 1/54 | 0/137 | - |
| P50 | F | 60 | m | Short-term memory impairment, parkinsonism, prefrontal symptoms | PARK7 | p.Ile91_Leu92fs c.273_274insA | het | D | P | - | AR | 1/54 | 0/137 | - |
| P35 | S | 61 | m | Short-term memory impairment, visuospatial disturbancy, dyscalculia, apraxia | SPG11 |
p. V2053M c.6157G > A rs149003934 |
het | VUS | VUS | < 0.01 | AR | 1/54 | 0/137 | [24] |
| P52 | F | 48 | f | Depression, memory impairment | PSAP | p.E108V c.323A > T rs763295469 | het | D | VUS | < 0.01 | AR | 1/54 | 0/137 | - |
From our biobanks, 55 healthy subjects and 82 patients without any neurodegenerative symptoms were selected as controls. F, familial; S, sporadic; AOO, age of onset; f, female; m, male; het., heterozygous; D, damaging; Conf. Of P., conflicting interpretations of pathogenicity; P, pathogenic; LP, likely pathogenic; VUS, variants with uncertain significance; AR, autosomal recessive; AD, autosomal dominant; MAF, minor allele frequency