背景:Bardet-Biedl综合征(BBS)和常染色体显性遗传性多囊肾病(ADPKD)是肾纤毛病变。BBS有22个致病基因,ADPKD主要由PKD1和PKD2变异体引起。具有BBS和PKD1的三等位基因变体的病例很少见。
方法:先证者是一名11岁的中国男性,双肾囊肿,视力模糊,远视,和短的手指和脚趾。由于肾功能衰竭的迅速恶化,患者接受了肾脏移植。随访期间,一个较小的视野,身高缓慢增加,并且观察到体重增加。此外,肾功能和贫血得到改善。高通量测序分析显示BBS2中有两个杂合变体(c.563delT(p。I188Tfs*13)遗传自父亲,c.5341G>t(剪接)来自母亲)和PKD1中的一个杂合变体(c.6223C>T(p。R2075C))继承自母亲。
结论:本文报道了1例有多等位基因变异(两个BBS2变异和一个PKD1变异)的纤毛病患者,可能导致早期症状和更快的进展。早期基因诊断可能有助于预测疾病进展,指导治疗和随访。
BACKGROUND: Bardet-Biedl syndrome (BBS) and autosomal dominant polycystic kidney disease (ADPKD) are renal ciliopathies. BBS has 22 pathogenic genes, and ADPKD is mainly caused by PKD1 and PKD2 variants. Cases with tri-allelic variants of BBS and PKD1 are rare.
METHODS: The proband was an 11-year-old Chinese male with cysts in both kidneys, blurred vision, hyperopia, and short fingers and toes. The patient underwent a kidney transplant due to rapid deterioration of renal failure. During follow-up, a smaller field of vision, a slow increase in height, and a weight gain were observed. In addition, renal function and anemia were improved. High-throughput sequencing analysis showed two heterozygous variants in BBS2 (c.563delT (p.I188Tfs*13) inherited from the father and c.534+1G > t (splicing) from the mother) and one heterozygous variant in PKD1 (c.6223C > T (p.R2075C)) inherited from the mother.
CONCLUSIONS: This paper reported a ciliopathy patient with multi-allelic variants (two BBS2 variants and one PKD1 variant) that may lead to early symptoms and more rapid progression. An early genetic diagnosis may contribute to predicting disease progression and guiding management and follow-up.