A Compound Heterozygous Mutation in the Ciliary Gene TTC21B Causes Nephronophthisis Type 12
A Compound Heterozygous Mutation in the Ciliary Gene TTC21B Causes Nephronophthisis Type 12
复制标题
DOI：
10.1055/s-0039-1700804
复制
发表时间：
2020-09-01
影响因子：
0.4
通讯作者：
Al-fiky, Amira Fathy
中科院分区：
文献类型：
--
作者：
El Fotoh, Wafaa Moustafa M. Abo;Al-fiky, Amira Fathy
肾病综合征（NPHP）是一种常染色体隐性遗传的肾脏囊性病变，通常进展为终末期肾病（ESRD）。它影响儿童、青少年和年轻人。在大约15%的病例中，会出现纤毛病变综合征的特征，包括肝纤维化、骨骼异常、视网膜异常和神经发育迟缓。我们描述的情况下，2岁的男性儿童与终末期肾病血液透析和家庭记录类似的条件（他的兄弟）。这个孩子的临床特点是简明扼要的总结。使用全外显子组测序进行遗传研究。TTC21B突变变异体在我们的患者中检测到，该患者表现为肾病范围的蛋白尿、局灶节段性肾小球硬化和肾小管间质病变，并演变为ESRD。未发现复合杂合突变，外显子6中的c.626c > t（p.P209L）和外显子5中的c.450g> a（p.W150Ter）。这些发现与常染色体隐性NPHP 12型的描述一致。NPHP的临床和病理诊断是至关重要的，记住ESRD以及其相关的肾外定义特征。TTC21B基因致病性变异的鉴定有助于NPHP12临床诊断的成功证明，并为正式合适的产前咨询提供信息。
Nephronophthisis (NPHP) is one of the renal ciliopathies and is also a cystic renal disorder with an autosomal recessive inheritance, which usually progresses to end-stage renal disease (ESRD). It affects children, adolescents, and young adults. In approximately 15% of cases, the features of a ciliopathy syndrome, which include liver fibrosis, skeletal anomalies, retinal abnormalities, and neurodevelopmental delay, will be present. We describe a case of a 2-year-old male child with ESRD on hemodialysis and a family record of a similar condition (his brother). The clinical features of this child are succinctly summarized. The genetic study was conducted using whole exome sequencing. TTC21B mutational variants were detected in our patient who exhibited nephrotic-range proteinuria, focal segmental glomerulosclerosis, and tubulointerstitial lesions that evolved to ESRD. Compound heterozygous mutations, c.626c > t (p.P209L) in exon 6 and c.450 g > a (p.W150Ter) in exon 5, were uncovered. These findings are in line with the description of autosomal recessive NPHP type 12. Both clinical and pathological diagnoses of NPHP are critical, bearing in mind ESRD as well as its related extrarenal defining features. Identification of the pathogenic variants in the TTC21B gene assisted in the successful proof of the clinical diagnosis NPHP12 as well as providing information for formal suitable prenatal counseling.