新型多等位基因突变，两种 BBS2 和一种 PKD1 变异，与肾脏纤毛病变相关：病例报告及文献复习。

Novel multi-allelic variants, two BBS2 and one PKD1 variant, of renal ciliopathies: A case report and literature review.

机构信息

Guangzhou Medical University Affiliated Guangzhou Women and Children's Medical Center, Guangzhou, China.

出版信息

Eur J Med Genet. 2023 Jun;66(6):104753. doi: 10.1016/j.ejmg.2023.104753. Epub 2023 Mar 30.

DOI:10.1016/j.ejmg.2023.104753

PMID:37003573

Abstract

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.

CASE PRESENTATION

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.

CONCLUSION

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.

摘要

背景

Bardet-Biedl 综合征（BBS）和常染色体显性多囊肾病（ADPKD）是肾脏纤毛病。BBS 有 22 个致病基因，ADPKD 主要由 PKD1 和 PKD2 变异引起。BBS 和 PKD1 三等位变异的病例很少见。

病例介绍

先证者是一名 11 岁的中国男性，患有双侧肾脏囊肿、视力模糊、远视以及短指（趾）。因肾衰竭迅速恶化，患者接受了肾移植。在随访过程中，发现视野较小、身高增长缓慢和体重增加。此外，肾功能和贫血得到改善。高通量测序分析显示，BBS2 有两个杂合变异（c.563delT [p.I188Tfs*13] 来自父亲，c.534+1G>T [剪接] 来自母亲），PKD1 有一个杂合变异（c.6223C>T [p.R2075C]）来自母亲。