Aging-US: 181 reported CHST6 variants in patients with macular corneal dystrophy09-08-2021
Aging-US published a Special Collection on Eye Disease which included "A comprehensive evaluation of 181 reported CHST6 variants in patients with macular corneal dystrophy" which reported that macular corneal dystrophy is an autosomal recessive disease featured by bilateral progressive stromal clouding and loss of vision, consequently necessitating corneal transplantation.
In this study, the authors integrated all the reported CHST6 variants described in 408 MCD cases, and performed a comprehensive evaluation to better illustrate the causality of these variants. In addition, the results underscored the strong correlation between mutant frequency and residue conservation in the general population, thus providing potential candidate targets for further genetic manipulation.
Dr. Jianjiang Xu from The Fudan University said, "Macular corneal dystrophy (MCD; OMIM 217800) is an autosomal recessive disease featured by bilateral progressive stromal clouding and loss of vision, finally necessitating corneal transplantation."
The CHST6 gene spans approximate 23 kb of the short arm of chromosome 16 and consists of 4 exons and a 1,187 bp open reading frame. The encoded protein CHST6 contains 395 amino acids with a molecular weight of 44 kDa. Variants in CHST6 gene have been recognized as the most critical genetic components in MCD. To date, more than 100 frameshift, nonsense, or missense variants in CHST6 were described in patients with MCD I/IA.
In MCD II patients, large rearrangements and deletions in the upstream of CHST6 were initially reported, followed by subsequent identification of mutations within the coding region of CHST6. However, substantial genetic heterogeneity still exists, and there is no study systematically evaluating CHST6 variants in MCD patients, in particular with regards to genotype-phenotype correlation and informing on the significance of specific variants. In the current study, the authors conducted a comprehensive evaluation of all 181 CHST6 variants described in MCD patients, and then classified the pathogenicity of those variants according to the American College of Medical Genetics and Genomics guidelines.
Figure 4. The normalized conservation scores (blue curve) for each residue in CHST6 protein and the percentage of reported MCD patients who carried mutations in the corresponding position (red curve).
The Xu Research Team concluded in their Aging-US Research Output, "the current comprehensive evaluation contributed to the most updated in-silico classification of all reported CHST6 variants till now. Although the vast majority of CHST6 variants are likely to be protein damaging, systematic functional investigations are still in urgent need to demonstrate the pathogenicity of these variants."
Full Text - https://www.aging-us.com/article/101807/text
Correspondence to: Jianjiang Xu email: firstname.lastname@example.org
Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research as well as topics beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, cancer, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR among others), and approaches to modulating these signaling pathways.