Table 1.
Summary of main early-onset motor neuronopathies
| Gene symbol | OMIM ref | Inheritance | Protein/Function | Associated conditions |
|---|---|---|---|---|
| Conditions with predominant distal involvement | ||||
| HSPB1 | 608634 | AD/AR | UPR; stabilization of microtubules? | HMN2B, CMT2F |
| HSPB8 | 158590 | AD | UPR | HMN2A, CMT2L |
| HSPB3 | 613376 | AD | - | HMN2C, CMT2 |
| ATP7A | 300489 | X-linked | Copper transport | X-linked HMN (SMAX3) |
| WARS | 617721 | AD | Tryptophanyl-tRNA synthetase | HMN9 |
| FBXO38 | 615575 | AD | Transcriptional activator | HMN2D |
| DNAJB2 | 614881 | AR | Co-chaperone | DSMA5 |
| HINT1 | 137200 | AR | Purine phosphoramidase | HMN with neuromyotonia |
| IGHMBP2 | 604320 | AR | Helicase | HMN6/SMARD, CMT2S |
| GARS | 600794 | AD | Aminoacyl-tRNA synthetases. Disruption of the VEGF/Nrp1 signalling pathway? | CMT2D, HMN5A, SMARD like phenotype |
| REEP1 | 614751 | AD | ER-mitochondrial interactions | HMN5B, HSP31 |
| BSCL2 | 619112 | AD | UPR | HMN5C, Silver syndrome |
| TRPV4 | 600175, 181405 | AD | Ion channel—possible disruption of mitochondrial axonal trafficking | HMN7, CMT2C, SPSMA, AMC, skeletal dysplasia |
| SLC5A7 | 158580 | AD | Presynaptic choline transporter | HMN7A, CMS 20 |
| DCTN1 | 607641 | AD | Axonal transport along the microtubules | HMN7B, juvenile ALS, Perry syndrome |
| SIGMAR1 | 605726 | AR | ER chaperone | DSMA2, Juvenile ALS |
| SETX | 606002, 602433 | AR, AD |
RNA and DNA helicase | HMN + pyramidal |
| AAAS | 231550 | AR | Nuclear protein import | Triple A syndrome |
| SORD | 618912 | AR | Oxidation of sorbitol to fructose | N/A |
| COQ7 | *601683 | AR | Coenzyme Q10 biosynthesis | N/A |
| MFN2 | n/a | AD | Mitochondrial fusion | CMT2A |
| SMA-LED or neuronopathies with early proximal weakness | ||||
| DYNC1H1 | 58600 | AD | Axonal retrograde transport + other housekeeping functions | SMALED 1, HMN1, AMC, ID + MCD |
| BICD2 | 615290, 618291 | AD | Cargo adaptor protein, interact with dynein/kinesin complex. Localize Rab6 to Golgi | SMALED2A, SMALED2B, AMC |
| SYT2 | 616040 | AD | Ca2+ sensors for vesicular trafficking and exocytosis | Presynaptic CMS (AR) |
| PLEKHG5 | 611067 | AR | Nuclear factor kappa-B activator | CMT-RIC |
| VWA1 | 619216 | AR | ECM component | N/A |
AMC = arthrogryposis multiplex congenita; CMT = Charcot Marie Tooth; CMS = congenital myasthenic syndrome; HSP = hereditary spastic paraplegia; ID = intellectual disability; LL = lower limbs; MCD = malformation of cortical development; UL = upper limbs; UPR = unfolded protein response.
A more comprehensive table describing salient clinical features and age of onset is provided in the Supplementary material.