Table 1.
Dolichol-dependent glycosylation genes with variants identified in the PME cohort
| Patient ID country of origin | Sex | Gene (GenBank) | Variant(s) (LOVD ID) | gnomAD MAF | Inheritance | Clinical summary (onset age) | WES study design | Confidence |
|---|---|---|---|---|---|---|---|---|
| PME1 Italy | M | NUS1 (NM_138459.3) | c.740dupT (p.Asp248Glyfs∗15) (het) (#00334867) | 0 | de novo | myoclonus (13y), no seizures; no ataxia, normal cognition | trio | high |
| PME2 Italy | F | NUS1 (NM_138459.3) | c.310delG (p.Val104∗) (het) (#00334873) | 0 | de novo | absence with eyelid myoclonia (4y); myoclonus (8y); ataxia, moderate cognitive impairment; febrile seizures (4y) with developmental regression | trio | high |
| PME3 Italy | M | DHDDS (NM_024887.3) | c.632G>A (p.Arg211Gln) (het) (#00334875) | 0 | de novo | myoclonus (7y); absences with eyelid myoclonia (9y); mild ataxia, moderate cognitive impairment; developmental delay | trio | high |
| PME71 Italy | F | DHDDS (NM_024887.3) | c.614G>A (p.Arg205Gln) (het) (#00334877) | 0 | unknown | ataxia (late infancy); rare TCS (17y), mild action myoclonus (29y); normal cognition | singleton | moderate |
| PME27 Italy | F | DHDDS (NM_024887.3) | c.283G>A (p.Asp95Asn) (het) (#00334878) | 0 | unknown | tremor (21y); myoclonus (35y), single TCS (36y); ataxia, normal cognition; bilateral deafness | singleton | moderate |
| PME50 Turkey | F | ALG10 (NM_032834.4) | c.1170_1171delAA (p.Lys391Valfs∗35)(hom) (#00334880) | 0 | AR | frequent myoclonus (13y), rare TCS; ataxia, mild cognitive dysfunction (16y); scoliosis | trio | moderate |
Abbreviations: MAF, minor allele frequency; AR, autosomal recessive; het, heterozygous; hom, homozygous; gnomAD, The Genome Aggregation Database; TCS, tonic-clonic seizure. Detailed clinical summaries can be found in Table S5. See subjects and methods for criteria for classifying variants as high versus moderate confidence.