Splicing Mutation and Single Gene Inheritance Disease

TANG Jiao¹, HAO Shengju^2,3, YANG Ruiqiong^2,3, WANG Yupei^2,3*, HUI Ling^2,3*

(¹School of Public Health, Gansu University of Chinese Medicine, Lanzhou 730000, China; ²Medical Genetics Center, Gansu Provincial Maternity and Child-Care Hospital, Lanzhou 730050, China; ³Gansu Provincial Clinical Research Center for Birth Defects and Rare Diseases, Lanzhou 730050, China)

Abstract:

pre-mRNA splicing is a key step in eukaryotic gene expression. Correct pre-mRNA splicing is highly dependent on the correct recognition of exons by spliceosomes, which is regulated by “cis” action elements and “trans” action factors involved in splicing. Splicing mutations can cause skipping or fragment loss of exons in mRNA and inclusion of intron fragments or pseudo exons. Therefore, studies suggest that splicing mutations are associated with many monogenic genetic diseases. This article reviews the interaction mechanism between cis-acting elements and trans-acting factors during splicing, analyzes the causes of monogenic genetic diseases caused by different types of splicing mutations, and summarizes the current verification methods and treatment methods for monogenic genetic diseases caused by splicing mutations. The in-depth study on the pathogenic mechanism of splicing mutation is of great significance for the clinical diagnosis of single gene inheritance disease and the research and development of targeted therapeutic drugs.

CSTR: 32200.14.cjcb.2022.10.0009