Group of Genetics and Developmental Biology of Renal Disease, Laboratory of Nephrology, No. 11, Health Research Institute of Santiago de Compostela (IDIS), Clinical University Hospital (CHUS), 15706 Santiago de Compostela, Spain.
Genomic Medicine Group, Clinical University Hospital (CHUS), 15706 Santiago de Compostela, Spain.
Int J Mol Sci. 2024 Oct 2;25(19):10609. doi: 10.3390/ijms251910609.
The gene, located on chromosome 17q12, encodes a transcription factor essential for the development of several organs. It regulates the expression of multiple genes in renal, pancreatic, hepatic, neurological, and genitourinary tissues during prenatal and postnatal development, influencing processes such as nephrogenesis, cellular polarity, tight junction formation, cilia development, ion transport in the renal tubule, and renal metabolism. Mutations that alter the function of Hnf1b deregulate those processes, leading to various pathologies characterized by both renal and extrarenal manifestations. The main renal diseases that develop are polycystic kidney disease, hypoplastic or dysplastic kidneys, structural abnormalities, Congenital Anomalies of the Kidney and Urinary Tract (CAKUT), and electrolyte imbalances such as hyperuricemia and hypomagnesemia. Extrarenal manifestations include Maturity-Onset Diabetes of the Young (MODY), hypertransaminasemia, genital and urinary tract malformations, Autism Spectrum Disorder (ASD), and other neurodevelopmental disorders. Patients with alterations typically carry either punctual mutations or a monoallelic microdeletion in the 17q12 region. Future research on the molecular mechanisms and genotype-phenotype correlations in -related conditions will enhance our understanding, leading to improved clinical management, genetic counseling, monitoring, and patient care.
该基因位于 17 号染色体 q12 上，编码一种转录因子，对多个器官的发育至关重要。它在产前和产后发育过程中调节肾脏、胰腺、肝脏、神经和泌尿组织中多个基因的表达，影响肾发生、细胞极性、紧密连接形成、纤毛发育、肾小管离子转运和肾脏代谢等过程。改变 Hnf1b 功能的突变会使这些过程失调，导致各种具有肾内和肾外表现的病理改变。主要发生的肾脏疾病有多囊肾病、肾脏发育不全或发育不良、结构异常、肾脏和泌尿道先天性异常（CAKUT）以及电解质失衡，如高尿酸血症和低镁血症。肾外表现包括青少年发病的成年型糖尿病（MODY）、高转氨酸血症、生殖器和泌尿道畸形、自闭症谱系障碍（ASD）和其他神经发育障碍。改变的患者通常携带点突变或 17q12 区域的单等位基因微缺失。对 -相关疾病的分子机制和基因型-表型相关性的未来研究将增强我们的认识，从而改善临床管理、遗传咨询、监测和患者护理。
