Gaefke Claudia L, Metts Jonathan, Imanirad Donya, Nieves Daime, Terranova Paola, Dell'Orso Gianluca, Gambineri Eleonora, Miano Maurizio, Lockey Richard F, Walter Jolan Eszter, Westermann-Clark Emma
Department of Medicine, University of South Florida, Tampa, FL, United States.
Cancer and Blood Disorders Institute, Johns Hopkins All Children's Hospital, Saint Petersburg, FL, United States.
Front Pediatr. 2021 Mar 18;9:624116. doi: 10.3389/fped.2021.624116. eCollection 2021.
Autoimmune Lymphoproliferative Syndrome (ALPS), commonly caused by mutations in the gene, is a disease with variable penetrance. Subjects may be asymptomatic, or they may present with lymphadenopathy, splenomegaly, cytopenias, or malignancy. Prompt recognition of ALPS is needed for optimal management. We describe a multi-generational cohort presenting with clinical manifestations of ALPS, and a previously unreported heterozygous missense variant of uncertain significance in (c.758G >T, p.G253V), located in exon 9. Knowledge of the underlying genetic defect permitted prompt targeted therapy to treat acute episodes of cytopenia. This cohort underscores the importance of genetic testing in subjects with clinical features of ALPS and should facilitate the reclassification of this variant as pathogenic.
自身免疫性淋巴细胞增生综合征（ALPS）通常由该基因的突变引起，是一种具有可变外显率的疾病。患者可能无症状，也可能出现淋巴结病、脾肿大、血细胞减少或恶性肿瘤。为了实现最佳管理，需要及时识别ALPS。我们描述了一个呈现ALPS临床表现的多代队列，以及一个位于第9外显子的、先前未报道的意义不确定的杂合错义变体（c.758G>T，p.G253V）。对潜在遗传缺陷的了解使得能够及时进行靶向治疗，以治疗血细胞减少的急性发作。该队列强调了对具有ALPS临床特征的患者进行基因检测的重要性，并应有助于将该变体重新分类为致病性变体。
