Table 1.
Pathogenic and Likely Pathogenic Variants in SHE-Associated Genes
| Gene | c.DNA Nucleotidic Change | Protein Aminoacidic Change | Mutation Type | Inheritance | Frequency of Pathogenic Variants | Function Effects |
|---|---|---|---|---|---|---|
| CHRNA416,17 | c.851C>T | p.Ser284Leu | Missense | Autosomal dominant (ADSHE) | 2.9% | Increased sensitivity to ACh |
| c.851C>G | p.Ser284Trp | Missense | ||||
| c.920G>T | p.Gly307Val | Missense | ||||
| CHRNB218–20 | - | V287L | Missense | Rare | ||
| - | V287M | |||||
| CHRNA221 | Ile279Asn | Non-synonymous substitution | Rare | |||
| c.754T>C | p.Tyr252His | Missense | ||||
| KCNT116,23,26 | c.2800G>A | p.Ala934Thr | Missense | De novo | 1% | Domain allosterically regulate channel opening and potassium ion permeation |
| c.1193G>A | p.Arg398Gln | |||||
| c.2386T>C; | p.Tyr796His | |||||
| c.2782C>T; | p.Arg928Cys | |||||
| c.2688G>A; | p.Met896Ile | |||||
| c.862G>A | p.Gly288Ser | |||||
| DEPDC516,33,34 | c.1165dupC | p.Arg389Profs*2 | Frameshift | Unknown | 3.9% the highest | Loss of inhibition of the mTOR pathway, resulting in overproliferation. Warning of FCDs |
| c.1264C>T | p.Arg422* | Nonsense | Paternal | |||
| c.193+1G>A | p.(?) | Canonical splice- site variant | Maternal | |||
| c.1225delA | p.Thr409Hisfs*15 | Frameshift | Unknown | |||
| NPRL235 | c.314T>C | p.Leu105Pro | Missense | Maternal | 1% | Changing the GATOR1 protein complex, thus affecting the mTOR-signaling pathway |
| c.100 C>T | p.Arg34* | |||||
| NPRL335 | c.835_836insT | p.Ser279Phe fs*52 | Frameshift | Unknown | - | |
| CRH37–39 | c. 89C>G | p.Pro30Arg | Missense | Unknown | Alter the ability of the cell to promptly produce, process and secrete the mature hormone | |
| PRIMA110,40 | c.93+2T>C | knockout of PRIMA1. | Splice site | Autosomal recessive (ARSHE) | – | Enhanced cholinergic responses |
| STX1B42 | C.106–2A>G | – | Aberrant splicing/mRNA decay | – | ||
| CABP441 | c.464G>A | p.G155D | Missense | Unknown | – | Decreases ion channel activation, leading to reduced Ca2+ concentrations |
| PPT142 | c.433G>C | p.G145R | – | Autosomal recessive (ARSHE) | – | Neuronal ceroid lipofuscinosis |
| Tsc143 | c.843del | p.Ser282Glnfs*36 | Unknown | Unknown | (mTOR) cascade dysfunction |
Notes: Modyfied with permission from Licchetta L, Pippucci T, Baldassari S, et al. Sleep-related hypermo-tor epilepsy (SHE): contribution of known genes in 103 patients. Seizure. 2020;74:60–64. Copyright 2020, with permission from Elsevier.16
Abbreviations: SHE, sleep-related hypermotor epilepsy; ADSHE, autosomal dominant sleep-related hypermotor epilepsy; ARSHE, autosomal recessive sleep-related hypermotor epilepsy; Ach, acetylcholine; DEPDC5, pleckstrin domain-containing protein 5; NPRL, nitrogen permease regulator-like; GATOR1, gap activity toward rags 1; mTOR, mammalian target of rapamycin; FCD, focal cortical dysplasia; CRH, corticotropin-releasing hormone.