Isolated congenital vertebral anomaly and Sprengel's deformity in a WBP11 pathogenic variant

IF 1.6 4区 医学 Q3 GENETICS & HEREDITY
Bo Kyung Shin , Jaewon Kim , Myung Shin Kim , Dae-Hyun Jang
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引用次数: 0

Abstract

The pathogenic variant of WBP11 has been known as one of the various genetic causes of VACTERL syndrome. VACTERL syndrome is usually diagnosed with at least three clinical features of vertebral, heart, tracheal, esophageal, kidney, and limb anomalies. So far, only four WBP11 pathogenic variants have been documented from 13 patients, first and latest described in 2020. In this clinical report, we present a patient with an isolated vertebral anomaly and Sprengel's deformity, carrying a pathogenic variant of WBP11, representing a distinctive case of patient that has never been described before. An eight-month-old boy with a 5°–10° head tilt to the right was referred to our institution and the cervical X-ray imaging showed the vertebral anomaly. Three-dimensional (3D) volume-rendered computed tomography (CT) of the cervical spine revealed the fusion state of the right C2 and C3 facet joints. And the right shoulder appeared to be raised and right scapula elevation was identified in the 3D chest CT. In addition, whole genome sequencing presented a de novo novel WBP11 heterozygous pathogenic variant, with frameshift resulting in a loss of function. WBP11 is a cell cycle-related pleiotropic gene that encodes a pre-messenger RNA splicing factor involved in centriole duplication. Pathogenic variants in WBP11 are genetically implicated in the development of multiple congenital anomalies. Clinically, WBP11 has been previously associated with VACTERL syndrome. In this report, we document clinical manifestations, including vertebral anomalies and Sprengel's deformity. The findings presented in this report indicate that haploinsufficiency of WBP11, resulting from a heterozygous pathogenic variant, may give rise to a more diverse array of clinical phenotypes than previously documented.
WBP11致病性变异中孤立的先天性椎体异常和Sprengel畸形。
WBP11的致病变异已被认为是VACTERL综合征的各种遗传原因之一。VACTERL综合征通常诊断为至少三个临床特征,即椎体、心脏、气管、食管、肾脏和肢体异常。到目前为止,仅记录了来自13名患者的4种WBP11致病变异,首次和最新描述于2020年。在这个临床报告中,我们提出了一个孤立的椎体异常和Sprengel畸形的患者,携带WBP11的致病变异,代表了一个以前从未描述过的独特病例。一个8个月大的男婴,头部向右倾斜5°-10°,颈椎x线片显示椎体异常。颈椎三维(3D)体积渲染计算机断层扫描(CT)显示右侧C2和C3小关节的融合状态。胸部三维CT显示右肩隆起,右肩胛骨上凸。此外,全基因组测序显示了一种全新的WBP11杂合致病变异,其移码导致功能丧失。WBP11是一种细胞周期相关的多效性基因,其编码参与中心粒复制的前信使RNA剪接因子。WBP11的致病变异在遗传上与多种先天性异常的发展有关。临床上,WBP11先前与VACTERL综合征相关。在本报告中,我们记录了临床表现,包括椎体异常和Sprengel畸形。本报告的研究结果表明,由杂合致病变异引起的WBP11的单倍性不足可能会导致比以前文献记载的更多样化的临床表型。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
4.10
自引率
0.00%
发文量
193
审稿时长
66 days
期刊介绍: The European Journal of Medical Genetics (EJMG) is a peer-reviewed journal that publishes articles in English on various aspects of human and medical genetics and of the genetics of experimental models. Original clinical and experimental research articles, short clinical reports, review articles and letters to the editor are welcome on topics such as : • Dysmorphology and syndrome delineation • Molecular genetics and molecular cytogenetics of inherited disorders • Clinical applications of genomics and nextgen sequencing technologies • Syndromal cancer genetics • Behavioral genetics • Community genetics • Fetal pathology and prenatal diagnosis • Genetic counseling.
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