Hermansky-Pudlak综合征的快速诊断与分型

IF 2.6 3区 医学 Q2 CELL BIOLOGY
Yingzi Zhang, Teng Liu, Qingsong Yang, Qiaorong Huang, Jiayi Ai, Yefeng Yuan, Wei Li, Aihua Wei
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引用次数: 0

摘要

Hermansky-Pudlak综合征(HPS)的诊断方法包括基因测序、免疫印迹、电子显微镜(EM)和mepacrine染色的流式细胞术。然而,由于成本高、技术复杂和可用性有限,这些方法通常不适合临床常规使用。在这项研究中,我们使用甲哌辛和氟ozin -3染色的流式细胞术评估了致密颗粒(DGs)在HPS小鼠模型中的功能。然后,我们开发了一种标准化的、实用的基于流式细胞术的方案,并在HPS和眼皮肤白化病(OCA)患者中进行了验证,并通过全载电镜证实了这一点。在HPS小鼠模型(block -1、block -2、block -3和AP-3缺陷突变体)中,甲哌辛的摄取持续减少。氟ozin -3荧光显示亚型特异性锌失调,在block -1、block -2和AP-3突变体中水平升高,而在block -3突变体中水平降低。相比之下,OCA-6小鼠突变体在甲哌辛或氟ozin -3摄取方面没有显着变化。在HPS和非综合征性OCA患者中观察到类似的模式。我们的研究结果表明,该方案可以实现HPS的精确诊断和初步亚型分类,同时也有助于HPS与OCA的鉴别诊断。该方法为常规诊断技术提供了一种快速、临床可及的替代方法,也可适用于其他DG缺陷的存储池疾病。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Rapid Diagnosis and Subtyping of Hermansky-Pudlak Syndrome With Flow Cytometry Analysis

The diagnostic approaches for Hermansky-Pudlak Syndrome (HPS) include genetic sequencing, immunoblotting, electron microscopy (EM), and flow cytometry with mepacrine staining. However, these methods are often impractical for routine clinical use due to high cost, technical complexity, and limited availability. In this study, we evaluated dense granules (DGs) function in HPS mouse models using flow cytometry with mepacrine and FluoZin-3 staining. We then developed a standardized, practical flow cytometry-based protocol and validated it in patients with HPS and oculocutaneous albinism (OCA), which were confirmed by whole-mount EM. In HPS mouse models (BLOC-1, BLOC-2, BLOC-3, and AP-3 deficient mutants), mepacrine uptake was consistently reduced. FluoZin-3 fluorescence showed subtype-specific zinc dysregulation, with elevated levels in BLOC-1, BLOC-2, and AP-3 mutants but decreased levels in the BLOC-3 mutant. In contrast, the OCA-6 mouse mutant showed no significant changes in either mepacrine or FluoZin-3 uptake. Similar patterns were observed in HPS and non-syndromic OCA patients. Our findings indicate that the protocol can enable the precise diagnosis and preliminary subtype classification of HPS, while also facilitating differential diagnosis between HPS and OCA. This method offers a rapid, clinically accessible alternative to conventional diagnostic techniques and may also be applicable to other storage pool disorders with DG defects.

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来源期刊
Pigment Cell & Melanoma Research
Pigment Cell & Melanoma Research 医学-皮肤病学
CiteScore
8.90
自引率
2.30%
发文量
54
审稿时长
6-12 weeks
期刊介绍: Pigment Cell & Melanoma Researchpublishes manuscripts on all aspects of pigment cells including development, cell and molecular biology, genetics, diseases of pigment cells including melanoma. Papers that provide insights into the causes and progression of melanoma including the process of metastasis and invasion, proliferation, senescence, apoptosis or gene regulation are especially welcome, as are papers that use the melanocyte system to answer questions of general biological relevance. Papers that are purely descriptive or make only minor advances to our knowledge of pigment cells or melanoma in particular are not suitable for this journal. Keywords Pigment Cell & Melanoma Research, cell biology, melatonin, biochemistry, chemistry, comparative biology, dermatology, developmental biology, genetics, hormones, intracellular signalling, melanoma, molecular biology, ocular and extracutaneous melanin, pharmacology, photobiology, physics, pigmentary disorders
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