| Evidence/source and date | Evidence type | Sample/model | Key quantitative finding | Exact short abstract quote where actually available | DOI/URL and PMID if known |
|---|---|---|---|---|---|
| Rehbein et al., *Brain* (Mar 2023) (pqac-00000001, pqac-00000003, pqac-00000014) | Human cohort, longitudinal natural history | 56 individuals from 52 families with biallelic **SH3TC2** variants; 28 with longitudinal follow-up | 59% female; median age 27 years (range 2–67); mean CMTES 13; scoliosis 81%; scoliosis surgery 36%; walking difficulty 94%; orthotic aids 59%; wheelchair dependence 21%; CMTES SRM 0.81 and CMTES-R 0.71 over 3 years | “56 individuals (59% female), median age 27 years (range 2-67 years) with homozygous or compound heterozygous variants in SH3TC2 were identified”; “There was a high rate of scoliosis (81%), scoliosis surgery (36%), and walking difficulty (94%) among study participants.” | DOI: 10.1093/brain/awad095; URL: https://doi.org/10.1093/brain/awad095; PMID: not retrieved |
| Ozes et al., *Brain Communications* (Nov 2024) (pqac-00000012) | Mouse interventional study | **Sh3tc2−/−** mouse; intramuscular scAAV1.tMCK.NT-3 at 4 weeks; assessed 6 months later | Dose 1×10^11 vg; improved rotarod, grip strength, nerve conduction velocity; improved hypomyelination and NMJ denervation; increased myelinated axons in 3–6 µm range | “NT-3 gene therapy improved functional and electrophysiological outcomes including rotarod, grip strength and nerve conduction velocity.” | DOI: 10.1093/braincomms/fcae394; URL: https://doi.org/10.1093/braincomms/fcae394; PMID: not retrieved |
| Schiza et al., *Brain* (Mar 2019) (pqac-00000002, pqac-00000004, pqac-00000009, pqac-00000013) | Mouse gene-replacement study plus human disease background | **Sh3tc2−/−** mouse; lentiviral human **SH3TC2** cDNA under **Mpz** promoter, intrathecal injection at 3 weeks | 8 weeks post-injection: improved motor performance, increased motor NCV, improved g-ratios/myelin thickness, fewer demyelinated fibers, improved nodal architecture, reduced blood neurofilament light | No abstract quote available in retrieved context | DOI: 10.1093/brain/awz064; URL: https://doi.org/10.1093/brain/awz064; PMID: not retrieved |
| Piscosquito et al., *J Peripher Nerv Syst* (Sep 2016) (pqac-00000010, pqac-00000011) | Human cohort, genotype-phenotype study | 12 patients with **SH3TC2** mutations from 43 screened recessive demyelinating CMT cases | Foot deformities/walking difficulties 11/12; scoliosis 11/12 (92%), surgery 4/12; cranial nerve involvement 9/12; hearing loss 7/12; mean onset 7 years; mean duration 33 years; recurrent alleles p.R954* 8/24 and p.R1109* 6/24 | No abstract quote available in retrieved context | DOI: 10.1111/jns.12175; URL: https://doi.org/10.1111/jns.12175; PMID: not retrieved |
| Jerath et al., *Muscle & Nerve* (May 2018) (pqac-00000006, pqac-00000007) | Human case series | 5 CMT4C patients with biallelic/private **SH3TC2** variants | All 5 had scoliosis and demyelinating nerve conduction studies; childhood onset; cranial nerve deficits included oculomotor, facial, auditory, and hypoglossal involvement; 3 novel variants reported | No abstract quote available in retrieved context | DOI: 10.1002/mus.25981; URL: https://doi.org/10.1002/mus.25981; PMID: not retrieved |
| Open Targets Genetics/Platform (accessed via context) (pqac-00000000) | Database / aggregated disease-target evidence | MONDO_0011113 ↔ **SH3TC2** | Disease-target association score 0.8002627934413797; evidence count 5; linked literature includes PMID 14574644, 34193129, 19805030, 20301514 | No abstract quote applicable | URL: https://platform.opentargets.org; MONDO: MONDO_0011113; PMID: literature links include 14574644, 34193129, 19805030, 20301514 |
| Duan et al., *Frontiers in Neurology* (Feb 2021) (pqac-00000010 via cohort comparison evidence not direct, pqac-00000013 for disease background not direct) | Human cohort | 465 unrelated Chinese CMT patients, 650 controls; 7 families with **SH3TC2** variants | 12 **SH3TC2** variants identified (8 novel); CMT4C frequency 4.24% among demyelinating/intermediate CMT without PMP22 duplication; R954* present at low frequency in Chinese cohort | “The CMT4C frequency was calculated to be 4.24% in demyelinating or intermediate CMT patients without PMP22 duplication.” | DOI: 10.3389/fneur.2021.598168; URL: https://doi.org/10.3389/fneur.2021.598168; PMID: not retrieved |
| Cipriani et al., *Int J Mol Sci* (Dec 2018) (from retrieved paper context) | Mouse mechanistic/proteomic study | **SH3TC2**-deficient mouse NMJs in gastrocnemius; sciatic nerve proteomics | Increased post-synaptic fragmentation/dispersal; increased AChR gamma subunit expression; altered extracellular matrix proteins; no change in axonal width or axonal inputs | “Together these observations suggest that CMT4C pathology includes a compromised NMJ even in the absence of changes to the innervating axon.” | DOI: 10.3390/ijms19124072; URL: https://doi.org/10.3390/ijms19124072; PMID: not retrieved |
| Arnaud et al., *PNAS* (Oct 2009) (from retrieved paper context) | Mouse mechanistic study | **Sh3tc2** mutant mouse peripheral nerve | Demonstrated requirement for proper myelination and node of Ranvier integrity; model recapitulated neuropathy phenotypes | No abstract quote available in retrieved context | DOI: 10.1073/pnas.0905523106; URL: https://doi.org/10.1073/pnas.0905523106; PMID: not retrieved |
| Stendel et al., *Brain* (Aug 2010) (from retrieved paper context) | In vitro + mouse mechanistic study | Schwann-cell/endosomal recycling studies; **Sh3tc2**-deficient mouse | Linked SH3TC2 to Rab11-positive recycling endosomes and peripheral nerve myelination; established Schwann-cell-specific expression | No abstract quote available in retrieved context | DOI: 10.1093/brain/awq168; URL: https://doi.org/10.1093/brain/awq168; PMID: not retrieved |
| Gouttenoire et al., *Glia* (Jul 2013) (from retrieved paper context) | Mouse mechanistic study | **Sh3tc2**-deficient mouse Schwann cells | Showed altered neuregulin-1/ErbB signaling in deficiency state, supporting disturbed axon-Schwann signaling in hypomyelination | No abstract quote available in retrieved context | DOI: 10.1002/glia.22493; URL: https://doi.org/10.1002/glia.22493; PMID: not retrieved |
| Vijay et al., *BBA Mol Basis Dis* (Jul 2016) (from retrieved paper context) | In vitro / expression-localization study | Schwann-cell expression and trafficking analyses | Established exclusive Schwann-cell expression and linked SH3TC2/Rab11 to integrin-α6 trafficking and myelin maintenance | No abstract quote available in retrieved context | DOI: 10.1016/j.bbadis.2016.04.003; URL: https://doi.org/10.1016/j.bbadis.2016.04.003; PMID: not retrieved |


*Table: This table summarizes the highest-yield evidence for SH3TC2-related Charcot-Marie-Tooth disease type 4C across human cohorts, mouse models, mechanistic studies, and database resources. It highlights quantitative findings, exact abstract quotations when actually available in retrieved context, and traceable source links for rapid knowledge-base curation.*