背景:肾小管发育不全(RTD)是一种严重的疾病,预后不良,严重影响肾脏的近端小管,同时保持解剖学上正常的总体结构。RTD的遗传起源,涉及ACE中的变体,REN,AGT,和AGTR1基因,影响肾素血管紧张素系统(RAS)内的各种酶或受体。这种情况在产前表现为羊水过少,在产后表现为持续性无尿,严重难治性低血压,和颅骨骨化的缺陷。
方法:在本报告中,我们描述了一个女性患者的案例,尽管接受了多种血管加压药治疗,经历持续性低血压,最终导致5日龄的早逝。虽然有父母血缘关系的历史,无肾脏疾病家族史.来自父母的血液样品和患者的剩余DNA样品进行全基因组测序(WGS)。遗传分析揭示了血管紧张素II受体1型(AGTR1)基因中罕见的纯合功能缺失变异(NM_000685.5;c.415C>T;p.Arg139*)。
结论:这个案例突出了AGTR1基因功能缺失变异导致RTD的后果,其特点是出生时或新生儿期死亡率高。此外,我们提供了先前报道的AGTR1基因变异的全面综述,这是RTD最少遇到的遗传原因,以及它们相关的临床特征。
BACKGROUND: Renal tubular dysgenesis (RTD) is a severe disorder with poor prognosis significantly impacting the proximal tubules of the kidney while maintaining an anatomically normal gross structure. The genetic origin of RTD, involving variants in the ACE, REN, AGT, and AGTR1 genes, affects various enzymes or receptors within the Renin angiotensin system (RAS). This condition manifests prenatally with oligohydramninos and postnatally with persistent anuria, severe refractory hypotension, and defects in skull ossification.
METHODS: In this report, we describe a
case of a female patient who, despite receiving multi vasopressor treatment, experienced persistent hypotension, ultimately resulting in early death at five days of age. While there was a history of parental consanguinity, no reported family history of renal disease existed. Blood samples from the parents and the remaining DNA sample of the patient underwent Whole Genome Sequencing (WGS). The genetic analysis revealed a rare homozygous loss of function variant (NM_000685.5; c.415C > T; p.Arg139*) in the Angiotensin II Receptor Type 1 (AGTR1) gene.
CONCLUSIONS: This
case highlights the consequence of loss-of-function variants in AGTR1 gene leading to RTD, which is characterized by high mortality rate at birth or during the neonatal period. Furthermore, we provide a comprehensive review of previously reported variants in the AGTR1 gene, which is the least encountered genetic cause of RTD, along with their associated clinical features.