Biallelic variants in TTC21B as a rare cause of early-onset arterial hypertension and tubuloglomerular kidney disease.
Biallelic variants in TTC21B as a rare cause of early-onset arterial hypertension and tubuloglomerular kidney disease.
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DOI：
10.1002/ajmg.c.31964
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发表时间：
2022-03
影响因子：
3.1
通讯作者：
Sayer, John A.
中科院分区：
文献类型：
--
作者：
Olinger, Eric;Phakdeekitcharoen, Pran;Caliskan, Yasar;Orr, Sarah;Mabillard, Holly;Pickles, Charles;Tse, Yincent;Wood, Katrina;Sayer, John A.
关键词：
单基因疾病的肾脏通常影响肾小球或肾小管间质室产生一组独特的临床表型。例如，原发性局灶节段性肾小球硬化症（FSGS）的特征是肾小球瘢痕形成伴蛋白尿和高血压，而肾单位结核（NPHP）与间质纤维化和肾小管萎缩、盐耗和低至正常血压有关。对于这两种疾病，已经鉴定了越来越多的分别在肾小球滤过或初级纤毛稳态中起作用的非重叠基因。然而，编码IFFT 139的TTC21 B与肾小球和肾小管间质区室的疾病相关，并分别与足细胞细胞骨架和纤毛运输缺陷有关。从极端早发性高血压、蛋白尿和进行性肾脏疾病的病例报告以及英国基因组学10万基因组计划的数据开始，我们在这里说明了将这种混合表型分配给正确的遗传诊断的困难。仔细的文献综述支持这样的观点，即TTC21 B中的双等位基因（通常为低型）错义变体通常与早发性高血压以及FSGS和NPHP的组织学特征相关。增加对这种混合性肾小球和肾小管间质疾病的临床识别，通常具有典型纤毛病变的轻度或缺失特征，以及将TTC 21 B纳入早发性动脉高血压的基因组中，可能会缩短这种罕见的肾小管肾小球肾病患者的诊断过程。
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.
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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Zieg J