Basic Neuroscience · Neuropathology
Neurogenetics
High-yield neurogenetics: disease-causing genes by category, repeat-expansion disorders, ATPase mutations, channelopathies, and leukodystrophies.
Important genetic diseases
| Disorder | Chromosome | Gene / Protein |
|---|---|---|
| Brain disorders | ||
| CADASIL | 19 | NOTCH3 |
| Rett syndrome | MECP2 | |
| Lissencephaly | LIS1 – LISX1 (doublecortin) | |
| Epilepsy | ||
| Febrile, GEFS+, Dravet, Doose | SCN1A | |
| ADNFLE | Nicotinic acetylcholine receptor | |
| JME | EFHC1 (myoclonin) | |
| Movement disorders / Ataxia | ||
| DOPA-responsive dystonia (Segawa syndrome) | 14 | DYT5: GTP cyclohydrolase |
| PKAN | PANK2 | |
| Friedreich's ataxia | Frataxin | |
| Ataxia-telangiectasia | 11 | ATM |
| Episodic ataxia 1 | KCNA1: K channel | |
| Episodic ataxia 2 | CACNA1A: Ca channel | |
| Anterior horn cell | ||
| SMA 1 (Werdnig-Hoffmann) | 5 | SMN (survival motor neuron) |
| SMA 2 (Kugelberg-Welander) | 5 | SMN |
| Spinobulbar muscular atrophy (Kennedy's) | X | CAG repeat (androgen receptor protein) |
| Neuromuscular | ||
| CMT 1A | 17 | PMP22 duplication (peripheral myelin protein) |
| CMT 1B | MPZ (myelin protein zero) | |
| CMT 1E | PMP22 point mutation | |
| CMT 2 | MFN2 (mitofusin, mitochondrial protein) | |
| HNPP | PMP22 deletion or point mutation | |
| Duchenne / Becker | X | Dystrophin |
| Myotonic dystrophy | 19 | Myotonin (DMPK) |
| Familial (malignant) hyperthermia | Ryanodine receptor (RYR1) | |
| Hyperkalemic periodic paralysis | Na channel | |
| Hypokalemic periodic paralysis | Ca channel | |
| Thomsen's myotonia congenita | Cl channel | |
| Hyperekplexia | Glycine receptor | |
| Tumors / phakomatoses | ||
| Retinoblastoma | RB1 | |
| Pituitary adenoma | MEN1 | |
| Familial meningioma | Merlin | |
| NF1 | 17 | Neurofibromin: schwannoma, astrocytoma, optic nerve glioma, neurofibroma, meningioma |
| NF2 | 22 | Merlin: bilateral schwannomas, multiple meningiomas, astrocytomas, ependymomas |
| VHL | 3 | VHL: hemangioblastomas, renal angioma, RCC, pheochromocytoma |
Trinucleotide (and other) repeat expansions
| Disorder | Repeat | Gene / Protein |
|---|---|---|
| Huntington's | CAG | Huntingtin |
| SCA | CAG | Ataxin |
| Spinobulbar muscular atrophy (Kennedy's) | CAG | Androgen receptor |
| DRPLA | CAG | Atrophin |
| Friedreich's ataxia | GAA | Frataxin |
| Myotonic dystrophy | CTG | Myotonin (DMPK) |
| Fragile X syndrome (FRAXA) | CGG | FMR1 |
| Fragile X-associated tremor/ataxia (FXTAS) | CGG | FMR1 |
| Myotonic dystrophy type II | CCTG (tetranucleotide) | CNBP (ZNF9) |
| SCA type 10 | ATTCT (pentanucleotide) | ATXN10 |
ATPase mutations
| ATPase mutation | Disorder |
|---|---|
| ATP1A3 | Alternating hemiplegia of childhood |
| ATP7A | Menkes disease |
| ATP7B | Wilson disease |
Channelopathies
| Disorder | Gene | Ion channel |
|---|---|---|
| Hyperkalemic periodic paralysis | SCN4A | Sodium |
| Paramyotonia congenita | SCN4A | Sodium |
| Potassium-aggravated myotonia | SCN4A | Sodium |
| Myotonia congenita | CLCN1 | Chloride |
| Hypokalemic periodic paralysis | CACNA1S | Calcium |
| Familial hemiplegic migraine | CACNA1A | Calcium |
| Episodic ataxia 2 | CACNA1A | Calcium |
| Episodic ataxia 1 | KCNA1 | Potassium |
| Andersen-Tawil syndrome | KCNJ2 | Potassium |
| Hereditary hyperekplexia | GLRA1 | Glycine |
Leukodystrophies
| Disorder | Enzyme / Protein deficiency |
|---|---|
| Canavan | Aspartoacylase |
| Metachromatic leukodystrophy | Arylsulfatase A |
| Adrenoleukodystrophy | Defective very-long-chain fatty acid metabolism (ABCD1) |
| Krabbe | Galactocerebrosidase |
| Pelizaeus-Merzbacher | Proteolipid protein (PLP1) |
LIGHTS on RITE by Ahmed Koriesh