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DCX
doublecortin
The DCX gene provides instructions for the doublecortin protein, which is essential for the proper movement and positioning of nerve cells in the developing brain. The DCX gene plays a critical role in brain development by coding for the doublecortin protein.
DCX is located on the long (q) arm of chromosome X, at band Xq23. Arm ratio per GRCh38 - banding schematic.
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Overview
The DCX gene, or doublecortin, is fundamental for early brain development, particularly in guiding the migration of neurons. The protein produced from this gene, doublecortin, helps nerve cells move to their appropriate positions, a process vital for forming the complex structures of the brain.
Errors in the DCX gene can disrupt this delicate process, leading to a range of developmental abnormalities that affect brain structure and function.
What the gene does
The DCX gene provides the blueprint for the doublecortin protein, which is integral to neuronal migration. Doublecortin interacts directly with microtubules, which are rigid, hollow fibres that form the cytoskeleton, the internal structural framework of cells. By binding to microtubules, doublecortin helps to stabilise them.
This stabilisation is crucial because microtubules act as scaffolding within the cell, elongating in specific directions to propel neurons and alter the cytoskeleton, thereby facilitating the movement of nerve cells to their final destinations in the brain.
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Chromosome location
The DCX gene is situated on the X chromosome at position Xq23. This chromosomal location means that it is an X-linked gene, which can influence its inheritance pattern and expression in individuals.
Protein structure
The doublecortin protein consists of 365 amino acids. Its structure includes several key regions: a Disordered region spanning amino acids 11-31, followed by a Doublecortin 1 domain from amino acids 53-139. Further along the protein, there is a Doublecortin 2 domain located between amino acids 180-263, and another Disordered region from amino acids 275-365.
Key variants
Variants within the DCX gene can alter the function of the doublecortin protein, potentially leading to errors in neuronal migration during brain development. These genetic changes can range from single nucleotide changes to larger deletions or insertions, each with the potential to impact protein stability or function.
Sample of pathogenic variants
10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.478del | p.Gln160fs | Pathogenic | ★★☆☆ | Lissencephaly type 1 due to doublecortin gene mutation |
c.478dup | p.Gln160fs | Pathogenic | ★★☆☆ | Lissencephaly type 1 due to doublecortin gene mutation |
c.505C>T | p.Gln169Ter | Pathogenic | ★★☆☆ | Lissencephaly type 1 due to doublecortin gene mutation |
c.536C>G | p.Pro179Arg | Pathogenic/Likely pathogenic | ★★☆☆ | Lissencephaly type 1 due to doublecortin gene mutation |
c.544G>T | p.Val182Phe | Pathogenic/Likely pathogenic | ★★☆☆ | Lissencephaly type 1 due to doublecortin gene mutation |
c.681dup | p.Leu228fs | Pathogenic | ★★☆☆ | Abnormal cortical gyration |
c.684_685del | p.Tyr229fs | Pathogenic | ★★☆☆ | Lissencephaly type 1 due to doublecortin gene mutation |
c.703C>T | p.Gln235Ter | Pathogenic | ★★☆☆ | not provided |
c.705+1G>A | - | Pathogenic | ★★☆☆ | not provided |
c.706-2A>G | - | Pathogenic | ★★☆☆ | not provided |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Pathogenic variants in the DCX gene are associated with conditions characterised by abnormal brain development, particularly those affecting cortical organisation. These include isolated lissencephaly sequence, which involves a smooth cerebral surface rather than the typical folds, and subcortical band heterotopia, where neurons fail to complete their migration and form abnormal layers in the brain. Both conditions are linked to significant neurological challenges.
No disease links recorded for this gene in our reference set.
UK clinical status
The DCX gene is actively reviewed within the UK's genomic medicine programmes. It is classified as 'green' in the DDG2P panel and is included in the Early onset or syndromic epilepsy, Foetal anomalies (R21), Intellectual disability, and Malformations of cortical development panels, indicating its recognised clinical utility in these areas.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the primary function of the DCX gene?
The DCX gene provides instructions for producing the doublecortin protein, which is critical for guiding the movement of nerve cells (neurons) to their correct positions in the brain during its development.
What happens if there are variants in the DCX gene?
Variants in the DCX gene can lead to abnormal neuronal migration, resulting in conditions such as isolated lissencephaly sequence and subcortical band heterotopia, which are characterised by structural brain abnormalities and neurological problems.
Is the DCX gene associated with intellectual disability?
Yes, conditions resulting from DCX gene variants, such as isolated lissencephaly sequence, typically involve severe neurological issues, including intellectual disability.
References
- González-Morón D, Vishnopolska S, Consalvo D. Germline and somatic mutations in cortical malformations: Molecular defects in Argentinean patients with neuronal migration disorders. PloS one. 2017. PMID: 28953922
- Fry AE, Cushion TD, Pilz DT. The genetics of lissencephaly. American journal of medical genetics. Part C, Seminars in medical genetics. 2014. PMID: 24862549
- Bahi-Buisson N, Souville I, Fourniol FJ. New insights into genotype-phenotype correlations for the doublecortin-related lissencephaly spectrum. Brain : a journal of neurology. 2013. PMID: 23365099
- Friocourt G, Marcorelles P, Saugier-Veber P. Role of cytoskeletal abnormalities in the neuropathology and pathophysiology of type I lissencephaly. Acta neuropathologica. 2011. PMID: 21046408
- Liu JS. Molecular genetics of neuronal migration disorders. Current neurology and neuroscience reports. 2011. PMID: 21222180