PDF(Pubmed)
Abstract：
Recent evidence has implicated EFL1 in a phenotype overlapping Shwachman-Diamond syndrome (SDS), with the functional interplay between EFL1 and the previously known causative gene SBDS accounting for the similarity in clinical features. Relatively little is known about the phenotypes associated with pathogenic variants in the EFL1 gene, but the initial indication was that phenotypes may be more severe, when compared with SDS. We report a pediatric patient who presented with a metaphyseal dysplasia and was found to have biallelic variants in EFL1 on reanalysis of trio whole-exome sequencing data. The variant had not been initially reported because of the research laboratory\'s focus on de novo variants. Subsequent phenotyping revealed variability in her manifestations. Although her metaphyseal abnormalities were more severe than in the original reported cohort with EFL1 variants, the bone marrow abnormalities were generally mild, and there was equivocal evidence for pancreatic insufficiency. Despite the limited number of reported patients, variants in EFL1 appear to cause a broader spectrum of symptoms that overlap with those seen in SDS. Our report adds to the evidence of EFL1 being associated with an SDS-like phenotype and provides information adding to our understanding of the phenotypic variability of this disorder. Our report also highlights the value of exome data reanalysis when a diagnosis is not initially apparent.
摘要：
最近的证据表明EFL1与Shwachman-Diamond综合征（SDS）的表型重叠有关，EFL1和先前已知的致病基因SBDS之间的功能相互作用解释了临床特征的相似性。对EFL1基因中与致病变异相关的表型知之甚少，但最初的迹象是表型可能更严重，与SDS相比。我们报告了一名儿科患者，该患者患有干phy端发育不良，并在重新分析三联全外显子组测序数据时发现EFL1具有双等位基因变异。由于研究实验室的重点是从头变体，因此最初没有报道该变体。随后的表型显示出她表现的变异性。尽管她的干phy端异常比最初报道的EFL1变异队列更严重，骨髓异常通常是轻度的，胰腺功能不全的证据模棱两可.尽管报告的患者数量有限，EFL1的变异似乎引起更广泛的症状,与SDS中的症状重叠.我们的报告增加了EFL1与SDS样表型相关的证据，并提供了增加我们对这种疾病表型变异性的理解的信息。我们的报告还强调了当诊断最初不明显时，外显子组数据重新分析的价值。
