# Rare VPS33B gene mutation combined with GP1BA mutation causes severe decrease in plasma VWF levels: a case report and literature review

## TL;DR

A rare combination of VPS33B and GP1BA gene mutations caused extremely low VWF levels in a patient, leading to a unique case of severe bleeding disorder.

## Contribution

First international report of VPS33B mutation causing reduced VWF levels and its combination with GP1BA mutation.

## Key findings

- Patient had FVIII and VWF levels below 1% despite no VWF gene mutations.
- VPS33B c.869G>C variant was found in the patient's father and correlated with reduced VWF levels.
- Combination of VPS33B and GP1BA mutations caused severe VWF deficiency not seen before.

## Abstract

一例28岁女性，孕期常规体检发现凝血因子Ⅷ活性（FⅧ∶C）<1％、血管性血友病因子抗原（VWF∶Ag）<1％。二代测序未发现其VWF基因外显子区域存在致病变异。由于该患者临床表现与Ⅲ型血管性血友病（VWD）临床特征不符，因此采用三代测序技术对该患者及其家系成员进行全基因组测序，发现该患者父系家族中有多位成员中携带VPS33B基因杂合变异c.869G>C，携带该变异的家系成员均有不同程度的VWF水平降低（39％～56％）。同时，先证者还检出GP1BA基因杂合变异c.1474dupA，ACMG及Clinvar数据库判断该变异与“血小板型假性VWD”相关。VPS33B基因杂合变异导致的VWF水平降低家系为国际首次报道，VPS33B基因与GP1BA基因双重杂合变异引起血浆VWF水平严重降低病例之前也未见报道。