Aldh7a1, encoding aldehyde dehydrogenase 7 family member A1, is a key enzyme in lysine oxidation. It is involved in pathways such as amino acid metabolism and is of great biological importance [3,6]. Genetic models can be valuable for studying its function.

Mutations in Aldh7a1 cause pyridoxine-dependent epilepsy (PDE), an autosomal recessive condition. The mutational spectrum is vast, and despite seizure control with pyridoxine, most patients have developmental delay and intellectual disability [1,3,4]. PDE may be more common than initially estimated, and newborn screening might be warranted [1]. Also, in oral cancer, Aldh7a1 expression is associated with pathologic nodal metastasis, cell migration, and prognosis, with high-expression patients having better outcomes [2]. In addition, the rs12514417 polymorphism of Aldh7a1 combined with alcohol exposure may increase the risk of ischemic stroke [5]. In lung squamous cell carcinoma, high expression of Aldh7a1 is an independent risk factor for poor prognosis, and it can promote tumor progression [7].

In conclusion, Aldh7a1 plays a crucial role in lysine oxidation and is associated with multiple diseases including pyridoxine-dependent epilepsy, oral cancer, ischemic stroke, and lung squamous cell carcinoma. The study of Aldh7a1 through genetic models helps to understand the mechanisms of these diseases and may provide potential targets for diagnosis and treatment.

References:

1. Coughlin, Curtis R, Swanson, Michael A, Spector, Elaine, Salomons, Gajja S, Van Hove, Johan L K. 2019. The genotypic spectrum of ALDH7A1 mutations resulting in pyridoxine dependent epilepsy: A common epileptic encephalopathy. In Journal of inherited metabolic disease, 42, 353-361. doi:10.1002/jimd.12045. https://pubmed.ncbi.nlm.nih.gov/30043187/

2. Lu, Hsueh-Ju, Chuang, Chun-Yi, Chen, Mu-Kuan, Lin, Chiao-Wen, Yang, Shun-Fa. 2022. The impact of ALDH7A1 variants in oral cancer development and prognosis. In Aging, 14, 4556-4571. doi:10.18632/aging.204099. https://pubmed.ncbi.nlm.nih.gov/35613852/

3. Coughlin, Curtis R, Tseng, Laura A, Abdenur, Jose E, Zuberi, Sameer M, van Karnebeek, Clara D M. 2020. Consensus guidelines for the diagnosis and management of pyridoxine-dependent epilepsy due to α-aminoadipic semialdehyde dehydrogenase deficiency. In Journal of inherited metabolic disease, 44, 178-192. doi:10.1002/jimd.12332. https://pubmed.ncbi.nlm.nih.gov/33200442/

4. Korasick, David A, Tanner, John J. 2020. Impact of missense mutations in the ALDH7A1 gene on enzyme structure and catalytic function. In Biochimie, 183, 49-54. doi:10.1016/j.biochi.2020.09.016. https://pubmed.ncbi.nlm.nih.gov/32956737/

5. Lin, Chun-Hsiang, Nfor, Oswald Ndi, Ho, Chien-Chang, Chen, Che-Hong, Liaw, Yung-Po. 2022. ALDH7A1 rs12514417 polymorphism may increase ischemic stroke risk in alcohol-exposed individuals. In Nutrition & metabolism, 19, 70. doi:10.1186/s12986-022-00702-3. https://pubmed.ncbi.nlm.nih.gov/36258220/

6. Wilson, Matthew P, Plecko, Barbara, Mills, Philippa B, Clayton, Peter T. 2019. Disorders affecting vitamin B6 metabolism. In Journal of inherited metabolic disease, 42, 629-646. doi:10.1002/jimd.12060. https://pubmed.ncbi.nlm.nih.gov/30671974/

7. Liang, Gaofeng, He, Jinxian, Chen, Tian, Yu, Kaizhong, Shen, Weiyu. 2024. Identification of ALDH7A1 as a DNA-methylation-driven gene in lung squamous cell carcinoma. In Annals of medicine, 57, 2442529. doi:10.1080/07853890.2024.2442529. https://pubmed.ncbi.nlm.nih.gov/39711312/