PBX1基因突变在先天性肾脏与尿路畸形中的研究进展OA

Congenital anomalies of the kidney and urinary tract(CAKUT)are a major cause of end-stage renal disease in children,and genetic factors play a significant role in the pathogenesis of CAKUT.CAKUT can be classified into syndromic and non-syndromic types depending on whether there is extrarenal involvement.Mutations in more than 50 single genes have been identified to cause syndromic CAKUT.Pre-B-cell leukemia transcription factor 1(PBX1)is a member of the three-amino-acid loop extension(TALE)homeodomain transcription factor family and can form complexes with proteins such as HOX and MEIS,playing an important regulatory role in embryonic development,especially in the development of the kidneys and urinary tract.In recent years,with the popularization of molecular diagnostic technologies such as whole-exome sequencing and gene chips,mutations in the PBX1 gene have been found to cause syndromic CAKUT.Since these gene mutations are rare,there is currently limited information on PBX1 gene function and genotype-phenotype correlations.Therefore,we explore the mechanisms by which PBX1 gene mutations lead to congenital kidney malformations and summarize the correlations between PBX1 gene mutations and phenotypes.Analysis shows that mutations in the HD domain have a mortality rate as high as 30％,mainly presenting as severe multisystem malformations,while mutations in the PBC domain primarily present as syndromic CAKUT.This provides a theoretical basis for personalized diagnosis,genetic counseling,and potential future therapies for CAKUT.