Department of Genetics, Hadassah Medical Organization, Jerusalem, Israel.
Department of Pediatrics & Genetics, Makassed Hospital, Al-Quds Medical School, E. Jerusalem, Palestine.
Eur J Med Genet. 2022 Jun;65(6):104513. doi: 10.1016/j.ejmg.2022.104513. Epub 2022 Apr 26.
RBL2/p130 is one of three highly conserved members of the retinoblastoma (RB) protein family. It is strongly upregulated during neuronal differentiation and brain development, and is critical for survival of post-mitotic neurons. Similar to RB1, it has been implicated as a tumor suppressor gene and has been shown to be dysregulated in various types of cancer. Recent publications describe biallelic, germline loss of function variants in RBL2 in individuals with profound developmental delay. We report a child with profound developmental delay, microcephaly, and hypotonia, who developed fulminant exophthalmos at age 6 years. Brain MRI followed by a biopsy of an intra-orbital mass revealed a mesenchymal tumor. Post-surgical histopathologic examination of the resected tumor was compatible with diagnosis of nodular fasciitis. Exome sequencing from peripheral blood identified a biallelic frameshift variant (c.901dupT) in RBL2. Notably, no malignancies were reported in previous cases with RBL2 variants. This case provides a possible association between RBL2 and orbital tumors.
RBL2/p130 是三种高度保守的视网膜母细胞瘤（RB）蛋白家族成员之一。它在神经元分化和大脑发育过程中强烈上调，对有丝分裂后神经元的存活至关重要。与 RB1 相似，它被认为是一种肿瘤抑制基因，并已在各种类型的癌症中显示失调。最近的出版物描述了 RBL2 中存在双等位基因、种系失活的功能变体，这些变体存在于具有严重发育迟缓的个体中。我们报告了一例患有严重发育迟缓、小头畸形和肌张力低下的儿童，他在 6 岁时出现暴发性眼球突出。眼部磁共振成像（MRI）后对眶内肿块进行活检，发现了一种间叶肿瘤。切除肿瘤的术后组织病理学检查与结节性筋膜炎的诊断相符。外周血外显子组测序发现 RBL2 中存在一个双等位基因移码变体（c.901dupT）。值得注意的是，以前 RBL2 变体病例中均未报告恶性肿瘤。该病例提供了 RBL2 与眼眶肿瘤之间的可能关联。
