Tan Queenie K-G, Cope Heidi, Spillmann Rebecca C, Stong Nicholas, Jiang Yong-Hui, McDonald Marie T, Rothman Jennifer A, Butler Megan W, Frush Donald P, Lachman Ralph S, Lee Brendan, Bacino Carlos A, Bonner Melanie J, McCall Chad M, Pendse Avani A, Walley Nicole, Shashi Vandana, Pena Loren D M
Department of Pediatrics, Division of Medical Genetics, Duke University Medical Center, Durham, North Carolina 27710, USA.
Institute for Genomic Medicine, Columbia University, New York, New York 10032, USA.
Cold Spring Harb Mol Case Stud. 2018 Oct 1;4(5). doi: 10.1101/mcs.a003046. Print 2018 Oct.
Recent evidence has implicated in a phenotype overlapping Shwachman-Diamond syndrome (SDS), with the functional interplay between and the previously known causative gene accounting for the similarity in clinical features. Relatively little is known about the phenotypes associated with pathogenic variants in the 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 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 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 appear to cause a broader spectrum of symptoms that overlap with those seen in SDS. Our report adds to the evidence of 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.
最近的证据表明，[基因名称]与一种与施瓦赫曼-戴蒙德综合征（SDS）重叠的表型有关，[基因名称]与先前已知的致病基因之间的功能相互作用解释了临床特征的相似性。关于[基因名称]致病变异相关的表型了解相对较少，但初步迹象表明，与SDS相比，这些表型可能更严重。我们报告了一名患有干骺端发育异常的儿科患者，在对三联体全外显子测序数据进行重新分析时发现其[基因名称]存在双等位基因变异。由于研究实验室专注于新发变异，该变异最初未被报告。随后的表型分析显示她的表现存在变异性。尽管她的干骺端异常比最初报告的携带[基因名称]变异的队列更为严重，但骨髓异常一般较轻，并且胰腺功能不全的证据不明确。尽管报告的患者数量有限，但[基因名称]变异似乎会导致更广泛的症状谱，与SDS所见症状重叠。我们的报告增加了[基因名称]与SDS样表型相关的证据，并提供了有助于我们理解这种疾病表型变异性的信息。我们的报告还强调了在最初诊断不明显时对全外显子数据进行重新分析的价值。
