Abstract：
Monogenic disorders of the kidney typically affect either the glomerular or tubulointerstitial compartment producing a distinct set of clinical phenotypes. Primary focal segmental glomerulosclerosis (FSGS), for instance, is characterized by glomerular scarring with proteinuria and hypertension while nephronophthisis (NPHP) is associated with interstitial fibrosis and tubular atrophy, salt wasting, and low- to normal blood pressure. For both diseases, an expanding number of non-overlapping genes with roles in glomerular filtration or primary cilium homeostasis, respectively, have been identified. TTC21B, encoding IFT139, however has been associated with disorders of both the glomerular and tubulointerstitial compartment, and linked with defective podocyte cytoskeleton and ciliary transport, respectively. Starting from a case report of extreme early-onset hypertension, proteinuria, and progressive kidney disease, as well as data from the Genomics England 100,000 Genomes Project, we illustrate here the difficulties in assigning this mixed phenotype to the correct genetic diagnosis. Careful literature review supports the notion that biallelic, often hypomorph, missense variants in TTC21B are commonly associated with early-onset hypertension and histological features of both FSGS and NPHP. Increased clinical recognition of this mixed glomerular and tubulointerstitial disease with often mild or absent features of a typical ciliopathy as well as inclusion of TTC21B on gene panels for early-onset arterial hypertension might shorten the diagnostic odyssey for patients affected by this rare tubuloglomerular kidney disease.
摘要：
肾脏的单基因疾病通常影响肾小球或肾小管间质区室，产生一组不同的临床表型。原发性局灶节段肾小球硬化（FSGS），例如,其特点是肾小球瘢痕形成，伴有蛋白尿和高血压，而nephronophthis（NPHP）与间质纤维化和肾小管萎缩有关，浪费盐,血压低到正常。对于这两种疾病，越来越多的非重叠基因在肾小球滤过或原发性纤毛稳态中发挥作用，分别,已被确认。TTC21B,编码IFT139，然而已经与肾小球和肾小管间质区室的疾病有关，并与足细胞细胞骨架和纤毛运输缺陷有关，分别。从一例极端早发性高血压的病例报告开始，蛋白尿,和进行性肾脏疾病，以及来自基因组英格兰100,000基因组项目的数据，我们在这里说明了将这种混合表型分配给正确的基因诊断的困难。仔细的文献综述支持双等位基因，通常是次形态，TTC21B中的错义变异通常与早发性高血压以及FSGS和NPHP的组织学特征相关。对这种混合性肾小球和肾小管间质性疾病的临床认识增加，通常具有轻度或不存在的典型纤毛病特征，以及在基因面板上包含TTC21B用于早发性动脉高血压，可能会缩短受这种罕见肾小管肾小球肾病影响的患者的诊断时间。
