PDF(Pubmed)
Abstract：
Monogenic nephrotic syndrome (NS) is associated with a resistance to initial glucocorticoid therapy and causative variants, which may be found in several genes influencing podocyte stability and kidney development. The TTC21B gene, which encodes the retrograde intraflagellar transport protein IFT139, is found mostly in association with ciliopathies in humans. The role of this protein in podocyte cytoskeleton stability was confirmed later and the mutated TTC21B also may be associated with proteinuric diseases, such as nephrotic syndrome. Our patient manifested as an infant with brachydactyly, nephrotic-range proteinuria, and renal tubular acidosis, and a kidney biopsy revealed focal segmental glomerulosclerosis (FSGS). Multiple phalangeal cone-shaped epiphyses of the hand were seen on X-ray. Next-generation sequencing revealed the well-described p.Pro209Leu heterozygous variant and a novel heterozygous p.Cys14Arg variant in the TTC21B gene. Our finding confirmed that the causative variants in the TTC21B gene may contribute to a spectrum of clinical features, such as glomerular proteinuric disease with tubulointerstitial involvement and skeletal abnormalities.
摘要：
单基因肾病综合征（NS）与对初始糖皮质激素治疗和致病变异的抵抗有关，这可能在几个影响足细胞稳定性和肾脏发育的基因中发现。TTC21B基因,它编码逆行滑膜内转运蛋白IFT139，主要与人类的纤毛病有关。该蛋白在足细胞细胞骨架稳定性中的作用后来得到证实，突变的TTC21B也可能与蛋白尿疾病有关。如肾病综合征。我们的病人表现为婴儿，肾病性蛋白尿，和肾小管酸中毒，肾活检显示局灶节段肾小球硬化（FSGS）。X线观察到手部的多个指骨锥形骨。下一代测序揭示了TTC21B基因中良好描述的p.Pro209Leu杂合变体和新的杂合p.Cys14Arg变体。我们的发现证实，TTC21B基因的致病变异可能有助于一系列临床特征，如肾小球蛋白尿疾病与肾小管间质受累和骨骼异常。
