Kaçar Dilek, Altan Mustafa, Bayhan Turan, Yıldırım Said Furkan, Kurtipek Fatma Burçin, Arman Bilir Özlem, Özbek Namık Yaşar, Yaralı Neşe
Department of Pediatric Hematology Oncology, Ankara Bilkent City Hospital, University of Health Sciences, Ankara 06800, Turkey.
Department of Medical Genetics, Ankara Bilkent City Hospital, Ankara 06800, Turkey.
Diagnostics (Basel). 2025 Aug 30;15(17):2210. doi: 10.3390/diagnostics15172210.
: Inherited platelet disorders (IPDs) are diverse conditions characterized by abnormalities in platelet count and function. Next-Generation Sequencing (NGS) shows promise as a diagnostic tool in the diagnosis of IPDs. This study aims to assess the clinical value and limitations of using a targeted NGS panel in diagnosing children with suspected IPDs. : We conducted a retrospective study of 93 children evaluated for suspected IPDs. A targeted NGS panel of 14 IPD-associated genes (, , , , , , , , , , , , , ) was performed. : Genetic variants were identified in 30 patients (32.3% of the cohort). A total of 37 variants, of which 15 (40.5%) were novel, were found across 11 of the 14 genes on the panel (all except , , and ). Variants were most frequently found in (18.9% of variants), (16.2%), and (16.2%) genes. The majority of variants (64.9%) were classified as variants of uncertain significance (VUS), followed by likely pathogenic (LP) (27%) and pathogenic (8.1%) variants. Most variants were in a heterozygous state (73%). Specific cases highlighted complex genetic scenarios, such as co-occurring variants, and the identification of pathogenic and LP variants in patients initially presenting with immune thrombocytopenia. : NGS helps to identify genetic causes, assess risk, manage, and provide genetic counseling in the management of IPDs. However, the prevalence of VUS underscores the need for a multidisciplinary approach to evaluate NGS results accurately.
遗传性血小板疾病（IPDs）是一类多样的病症，其特征为血小板计数和功能异常。下一代测序（NGS）作为IPDs诊断的工具显示出应用前景。本研究旨在评估使用靶向NGS panel诊断疑似IPDs儿童的临床价值和局限性。我们对93名接受疑似IPDs评估的儿童进行了一项回顾性研究。对14个与IPD相关的基因（，，，，，，，，，，，，，）进行了靶向NGS panel检测。在30名患者（占队列的32.3%）中鉴定出基因变异。共发现37个变异，其中15个（40.5%）是新变异，分布在检测板上14个基因中的11个基因上（除外，，和所有基因）。变异最常出现在（占变异的18.9%）、（16.2%）和（16.2%）基因中。大多数变异（64.9%）被分类为意义未明的变异（VUS），其次是可能致病（LP）（27%）和致病（8.1%）变异。大多数变异处于杂合状态（73%）。具体病例突出了复杂的遗传情况，如同时出现的变异，以及在最初表现为免疫性血小板减少症的患者中鉴定出致病和LP变异。NGS有助于在IPDs管理中识别遗传原因、评估风险、进行管理并提供遗传咨询。然而，VUS的高发生率强调了需要采用多学科方法来准确评估NGS结果。
