27 October 2020
Single mutation causes severe nerve-system syndrome
Published online 24 October 2013
The electrical signals that travel along nerve cells in the brain, heart, skeletal muscle, pituitary glands and pancreas are controlled by voltage-gated proteins that form channels across the cellular membrane, allowing ions to move in and out of the cell as the pulse propagates. Sodium leak channel, nonselective (NALCN) is one such voltage-gated channel-like protein.
Now, for the first time, a research team led by Namik Kaya from the King Faisal Specialist Hospital and Research Centre, Riyadh, has identified mutations in the NALCN gene in two unrelated families through a genome-wide scan of DNA extracted from the blood samples, publishing their results in the American Journal of Human Genetics.
The researchers found that a deletion of a single DNA base pair in the NALCN gene truncated the NALCN protein, disrupting the development of nerve cells in affected individuals who had impaired speech, impaired cognition with disrupted muscle activity, as well as chronic constipation.
One of the families employed preimplantation genetic diagnosis to screen fertilized embryos and healthy twins were born. Postnatal DNA analysis showed the twins have normal NALCN genes, suggesting that this genetic diagnostic tool can be used to avert NALCN-associated disorders.
- Al-Sayed, M. D. et al. Mutations in NALCN cause an autosomal-recessive syndrome with severe hypotonia, speech impairment, and cognitive delay. Am. J. Hum. Genet. 93, 1-6 (2013) | Article |