Ciliopathies constitute heterogeneous disorders that result from mutations in ciliary proteins. These proteins play an important role in the development of organs, physiology, and signaling pathways, and sequence variations in the genes encoding these proteins are associated with multisystem disorders. In this study, we describe a severe ciliopathy disorder that segregates in an autosomal recessive manner in a nonconsanguineous Saudi family. The proband exhibited features such as cholestasis, cystic dilatation of intrahepatic biliary ducts, diabetes insipidus, dysmorphic facial features, optic atrophy, pituitary hypoplasia, hydrocephalus, aqueductal stenosis, hyperextensible knee joints, bilateral knee dislocation, polydactyly, and syndactyly. Whole-genome sequencing and Sanger sequencing revealed a homozygous splice site variant (c.4–1G#x3e;C; NM_024926.3) in the tetratricopeptide repeat domain 26 (TTC26) gene located in chromosome 7q34, which cosegregated perfectly with the disease phenotype. qRT-PCR revealed a substantial decrease in the expression of the TTC26 gene as compared to the normal control, suggesting the pathogenicity of the identified variant. This report further strengthens the evidence that homozygous variants in the TTC26 gene cause severe ciliopathies with diverse phenotypes. We named this newly characterized condition as BRENS syndrome, which stands for biliary, renal, neurological, and skeletal features.
Mol Syndromol

中文翻译：

---

在具有胆道、肾脏、神经和骨骼表现的新型复杂纤毛病综合征中鉴定 TTC26 剪接变体

纤毛病构成由纤毛蛋白突变引起的异质性疾病。这些蛋白质在器官、生理和信号通路的发育中起着重要作用，编码这些蛋白质的基因的序列变异与多系统疾病有关。在这项研究中，我们描述了一种严重的纤毛病，它在一个非血缘的沙特家庭中以常染色体隐性方式分离。先证者表现出胆汁淤积、肝内胆管囊性扩张、尿崩症、面部畸形、视神经萎缩、垂体发育不全、脑积水、导水管狭窄、膝关节过度伸展、双侧膝关节脱位、多指畸形和并指畸形等特征。全基因组测序和 Sanger 测序揭示了一个纯合剪接位点变异 (c.4–1G#x3e;C;TTC26 ) 基因位于染色体 7q34，与疾病表型完全共分离。qRT-PCR 显示与正常对照相比，TTC26基因的表达显着降低，表明所鉴定变异的致病性。该报告进一步加强了TTC26基因中的纯合变异导致具有不同表型的严重纤毛病的证据。我们将这种新特征的疾病命名为 BRENS 综合征，它代表胆道、肾脏、神经和骨骼特征。
摩尔综合征