Table 1.
Brain malformations and genes associated with abnormal neuron positioning
| Type | Gene | Location | Description |
|---|---|---|---|
| Lissencephaly type I | |||
| Lissencephaly (Autosomal dominant) | LIS1 | 17p13.3 | Microtubule-associated protein |
| Isolated lissencephaly sequence (ILS) or subcortical band heterotopia (SBH) | TUBA1A | 12q13.12 | Constituent of microtubules |
| Miller-Dieker syndrome | LIS1 + YWHAE | 17p13.3 | Microtubule-associated protein |
| Lissencephaly (X-linked) | |||
| ILS or SBH | DCX | Xq22.3-q23 | Microtubule-associated protein |
| X-linked lissencephaly with abnormal genitalia | ARX | Xp21.3 | Transcription factor |
| Lissencephaly (Autosomal recessive) | |||
| Lissencephaly with cerebellar hypoplasia (LCH) group b | RELN | 7q22 | Extracellular matrix serine protease |
| VLDLR | 9q24 | Binds VLDL and transports it into cells by endocytosis | |
| Lissencephaly type II: Cobblestone complex (Autosomal recessive) | |||
| Fukuyama congenital muscular dystrophy or Walker–Warburg syndrome (WWS) | FKTN | 9q31.2 | Involved in glycosylation |
| Muscle–eye–brain disease (MEB) or WWS | POMT1 | 9q34.13 | Protein-O-mannosyltransferase 1 |
| POMT2 | 14q24.3 | Protein-O-mannosyltransferase 2 | |
| POMGNT2 | 3p22.1 | O-linked mannose acetylglucosaminyltransferase | |
| FKRP | 19q13.32 | Involved in glycosylation | |
| MEB | LARGE | 22q12.3 | Glycosyltransferase |
| POMGnT1 | 1p34.1 | Participates in O-mannosyl glycosylation | |
| Bilateral frontoparietal polymicrogyria | GPR56 | 16q21 | G protein-coupled receptor 56 |
| CEDNIK syndrome | SNAP29 | 22q11.21 | Synaptosomal-associated protein |
| Muscular dystrophy | ISPD | 7q21.2 | Required for protein O-linked mannosylation |
| GTDC2 | 3p22.1 | O-linked mannose acetylglucosaminyltransferase | |
| TMEM5 | 12q14.2 | Glycosyltransferase function | |
| B3GALNT2 | 1q42.3 | Beta-1,3-N-acetylgalactosaminyltransferase | |
| SGK196 | 8q11.21 | Protein O-mannose kinase | |
| B3GNT1 | 11q13.2 | Synthesis of the linear poly-N-acetyllactosaminoglycans | |
| GMPPB | 3p21.31 | GDP-mannose pyrophosphorylase | |
| Polymicrogyria | |||
| TUBB2 | 6p25 | Major constituent of microtubules | |
| GPR56 | 16q21 | G protein-coupled receptor 56 | |
| SRPX2 | Xq22.1 | Plays a role in angiogenesis | |
| TBR2 | 3p24.1 | Transcriptional activator | |
| PAX6 | 11p13 | Transcription factor | |
| KIAA1279 | 10q22.1 | Organization of axonal microtubules | |
| RAB3GAP1 | 2q21.3 | RAB3 GTPase Activating Protein Subunit | |
| Adams-Oliver syndrome (AOS) | ARHGAP31 | 3q13.33 | Required for cell spreading |
| AOS | RBPJ | 4p15.2 | Plays a central role in Notch signaling |
| AOS | DOCK6 | 19p13.2 | Atypical guanine nucleotide exchange factors |
| AOS | EOGT | 3p14.1 | EGF domain-specific GlcNAc transferase |
| AOS | NOTCH1 | 9q34.3 | Play multiple roles during development |
| Heterotopia | |||
| Heterotopia (X-linked Autosomal dominant) | |||
| Classical bilateral periventricular heterotopia (PH) | FLNA | Xq28 | Actin-binding protein |
| PH with fragile-X syndrome | FMR1 | Xq27.3 | Translation repressor |
| PH and Williams syndrome | WBSCR16 | 7q11.23 | Guanine nucleotide exchange factor |
| PH | PVNH3 | 5p15.1 | Periventricular Nodular Heterotopia 3 |
| PH | PVNH5 | 5q14.3-q15 | Periventricular Nodular Heterotopia 5 |
| Heterotopia (Autosomal recessive) | |||
| PH with microcephaly | ARFGEF2 | 20q13.13 | Intracellular vesicular trafficking |
| PH with Donnai–Barrow syndrome | LRP2 | 2q31.1 | Low density lipoprotein-related protein 2 |
| Microcephaly | |||
| WDR62 | 19q13.12 | Required for cerebral cortical development | |
| KIAA1279 | 10q22.1 | Organization of axonal microtubules | |
| RAB3GAP1 | 2q21.3 | RAB3 GTPase Activating Protein Subunit | |
| ARFGEF2 | 20q13.13 | Intracellular vesicular trafficking | |
| Focal cortical dysplasia | |||
| TSC1 | 9q34.13 | Negatively regulating mTORC signaling | |
| TSC2 | 16p13.3 | Negatively regulating mTORC signaling | |
| Hemimegalencephaly | |||
| PIK3CA | 3q26.32 | Serine/threonine kinase - component of PI3K/AKT signaling | |
| AKT3 | 1q44 | Serine/threonine kinase - component of PI3K/AKT signaling | |
| MTOR | 1p36.22 | Serine/threonine kinase – component of PI3K/AKT signaling |