| Gene (HGNC symbol) | Evidence type | Inheritance pattern as reported | Key variant(s)/mechanism | Phenotypic associations | Key citation |
|---|---|---|---|---|---|
| **DCC** | Human families/cases; cohort of 80 CMM individuals; in vitro commissural-neuron assays; Drosophila functional model (pqac-00000008, pqac-00000013) | Usually **heterozygous/monoallelic** for isolated CMM; **biallelic** loss-of-function causes developmental split-brain syndrome (DSBS) (pqac-00000011, pqac-00000013) | **R1343H** in cytoplasmic **WIRS** motif disrupts DCC–WAVE regulatory complex interaction, impairing netrin-1–DCC axon guidance; many other CMM-associated DCC variants localize to extracellular domain and can disrupt netrin-1 binding or cause truncation/haploinsufficiency (pqac-00000008) | Isolated CMM; agenesis/dysgenesis of corpus callosum; corticospinal/spinal commissural axon crossing defects; DSBS with more severe neurodevelopmental phenotype when biallelic (pqac-00000008, pqac-00000011, pqac-00000013) | Chaudhari et al., *Sci Signal* 2024, DOI: 10.1126/scisignal.adk2345, https://doi.org/10.1126/scisignal.adk2345 (pqac-00000008); Prato et al., *J Clin Med* 2024, DOI: 10.3390/jcm13041109, https://doi.org/10.3390/jcm13041109 (pqac-00000013) |
| **NTN1** | Human families and sporadic case; functional cell studies; human tract-anatomy studies; mouse model support (pqac-00000002, pqac-00000010, pqac-00000026) | Familial/sporadic **heterozygous** CMM reported; exact mode not always explicitly stated in excerpt (pqac-00000002, pqac-00000010) | **3 exon 7 mutations**; mutant netrin-1 proteins are retained **intracellularly** rather than secreted, implying loss of extracellular guidance cue function and abnormal CST decussation (pqac-00000002, pqac-00000010) | Isolated CMM; abnormal corticospinal tract anatomy/decussation; mirror-like symmetric movement in mouse Ntn1 deficiency model (pqac-00000002, pqac-00000010, pqac-00000026) | Méneret et al., *J Clin Invest* 2017, DOI: 10.1172/JCI95442, https://doi.org/10.1172/jci95442 (pqac-00000002, pqac-00000010); Hu et al., *Cell Death Dis* 2024, DOI: 10.1038/s41419-024-06719-1, https://doi.org/10.1038/s41419-024-06719-1 (pqac-00000026) |
| **RAD51** | Human family/case genetics; review synthesis (pqac-00000005, pqac-00000011) | **Haploinsufficiency** reported in humans; familial disease often described as autosomal dominant in review-level summaries (pqac-00000011, pqac-00000014) | **RAD51 haploinsufficiency** causes CMM; newer 2023 review highlights an unexpected noncanonical developmental role for RAD51 in brain development rather than classical cancer predisposition pathways (pqac-00000011) | Isolated/familial CMM; overlaps mechanistically with axon-guidance pathway disorders, though detailed callosal/CST phenotypes are less elaborated in provided excerpts (pqac-00000011, pqac-00000014) | Depienne et al., *Am J Hum Genet* 2012, DOI: 10.1016/j.ajhg.2011.12.002, https://doi.org/10.1016/j.ajhg.2011.12.002 (referenced in pqac-00000011); Thomas et al., *Cells* 2023, DOI: 10.3390/cells12081169, https://doi.org/10.3390/cells12081169 (from prior retrieval context) |
| **ARHGEF7** | Human autosomal-dominant family; biochemical/cellular studies; heterozygous mouse model (pqac-00000000) | **Autosomal dominant** MM pedigree reported (pqac-00000000) | Candidate MM gene encoding a **RhoGEF**; ARHGEF7 and partner **GIT1** bind directly to DCC, activate **Rac1/Cdc42**, inhibit **Arf1**, and mediate netrin-1–induced increase in cell-surface DCC (pqac-00000000) | Familial CMM/MM; commissural axon trajectory defects; MM-like increased symmetric paw placement in heterozygous mice (pqac-00000000) | Schlienger et al., *Sci Adv* 2023, DOI: 10.1126/sciadv.add5501, https://doi.org/10.1126/sciadv.add5501 (pqac-00000000) |
| **MCF2** | Two unrelated human male cases (adult and fetus); exome/genome sequencing; biochemical and cellular functional studies (pqac-00000006, pqac-00000012) | **X-linked/hemizygous** in affected males (pqac-00000006, pqac-00000012) | Recurrent **c.31C>T p.(R11W)**; MCF2 physically interacts with DCC, relocalizes DCC, and the R11W variant **disrupts DCC binding**, reduces DCC relocalization, and lowers GEF activity (pqac-00000006, pqac-00000012) | Adult male with CMM; fetal case with corpus callosum agenesis and abnormal corticospinal decussation; broader axon-guidance/commissural defect spectrum including arhinencephaly in excerpted discussion (pqac-00000006, pqac-00000011, pqac-00000012) | Accogli et al., preprint 2024, DOI: 10.21203/rs.3.rs-5227743/v1, https://doi.org/10.21203/rs.3.rs-5227743/v1 (pqac-00000006, pqac-00000012) |
| **DCC pathway support from models** | Mouse conditional knockout and zebrafish mutant models (pqac-00000026, pqac-00000029, pqac-00000030, pqac-00000031) | Not applicable | **Ntn1** ventricular-zone deletion in mouse causes CST defasciculation and failed pyramidal decussation with increased symmetric forelimb movements; zebrafish **dcc** mutants show ipsilateral misprojection of identified reticulospinal neurons sufficient to drive mirror movement-like behavior (pqac-00000026, pqac-00000029, pqac-00000030, pqac-00000031) | Confirms mechanistic link between defective midline crossing and mirror/symmetric motor output across vertebrate systems (pqac-00000026, pqac-00000029, pqac-00000030, pqac-00000031) | Hu et al., *Cell Death Dis* 2024, DOI: 10.1038/s41419-024-06719-1, https://doi.org/10.1038/s41419-024-06719-1 (pqac-00000026); Jain et al., *J Neurosci* 2014, DOI: 10.1523/JNEUROSCI.2420-13.2014, https://doi.org/10.1523/jneurosci.2420-13.2014 (pqac-00000029, pqac-00000030, pqac-00000031) |


*Table: This table summarizes the main genes implicated in familial congenital mirror movements and the mechanistic evidence linking them to defective axon guidance and corticospinal midline crossing. It highlights inheritance, representative variants, associated phenotypes, and key citations from the provided context.*