目的 分析1例Verheij综合征(VRJS)患儿的临床表型与基因变异，并探讨二者的相关性。 方法 选取2022年7月因"自幼高肩胛骨"就诊于苏州大学附属儿童医院骨科门诊和苏州市吴江区儿童医院多学科门诊的1例患儿作为研究对象。采集患儿及其父母的外周血样，对其进行全外显子组测序分析，并对候选变异进行Sanger测序验证。 结果 患儿表现为高肩胛骨、斜颈、上肢及肩关节活动受限、面容异常、皮肤散在咖啡斑，智力发育障碍等。测序结果显示其携带PUF60基因c.405dupT(p.Ile136Tyrfs*4)新发杂合变异。根据美国医学遗传学与基因组学学会(ACMG)相关指南判定为致病性(PVS1+PS2_moderate+PM2_supporting)。结合患儿的临床表型及基因检测结果，确诊其为PUF60基因c.405dupT变异所致的VRJS。 结论 VRJS临床表现为特殊面容、智力障碍及高肩胛骨、椎体横突融合畸形、肩椎骨形成等骨骼发育异常，心脏、肾脏、眼等部位无明显异常，不易与Klippel-Feil综合征相区别。本研究丰富了PUF60基因的变异谱，为明确VRJS基因型与表型的相关性提供了数据。 Objective To explore the clinical phenotype and genetic variant in a child with Verheij syndrome (VRJS). Methods A child who had presented at the Soochow University Affiliated Children′s Hospital and Wujiang District Children′s Hospital in July 2022 for "elevated scapula since early childhood" was selected as the study subject. Peripheral blood samples of the child and his parents were collected and subjected to whole exome sequencing. Candidate variant was verified by Sanger sequencing and bioinformatic analysis. Results The child had manifested elevated scapulae, torticollis, neck asymmetry, facial dysmorphism, dispersed café-au-lait spots, limited mobility of upper limbs and shoulder joints, and intellectual disability. Sequencing revealed that he has harbored a de novo heterozygous c. 405dupT (p.Ile136Tyrfs*4) variant of the PUF60 gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), this variant was classified as pathogenic (PVS1+ PS2_moderate+ PM2_supporting). Combined his clinical features and result of genetic testing, the child was diagnosed with VRJS due to variant of the PUF60 gene. Conclusion The clinical manifestations of VRJS include facial dysmorphism, intellectual disability, elevated scapulae, vertebral fusion, other skeletal malformations, without significant abnormalities of the heart, kidney, and eyes, which need to be distinguished from Klippel-Feil syndrome. Above finding has expended the mutation spectrum of the PUF60 gene and provided a reference for delineation of the genotype-phenotype correlation of the VRJS.
Abstract
Objective To explore the clinical phenotype and genetic variant in a child with Verheij syndrome (VRJS). Methods A child who had presented at the Soochow University Affiliated Children′s Hospital and Wujiang District Children′s Hospital in July 2022 for "elevated scapula since early childhood" was selected as the study subject. Peripheral blood samples of the child and his parents were collected and subjected to whole exome sequencing. Candidate variant was verified by Sanger sequencing and bioinformatic analysis. Results The child had manifested elevated scapulae, torticollis, neck asymmetry, facial dysmorphism, dispersed café-au-lait spots, limited mobility of upper limbs and shoulder joints, and intellectual disability. Sequencing revealed that he has harbored a de novo heterozygous c. 405dupT (p.Ile136Tyrfs*4) variant of the PUF60 gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), this variant was classified as pathogenic (PVS1+ PS2_moderate+ PM2_supporting). Combined his clinical features and result of genetic testing, the child was diagnosed with VRJS due to variant of the PUF60 gene. Conclusion The clinical manifestations of VRJS include facial dysmorphism, intellectual disability, elevated scapulae, vertebral fusion, other skeletal malformations, without significant abnormalities of the heart, kidney, and eyes, which need to be distinguished from Klippel-Feil syndrome. Above finding has expended the mutation spectrum of the PUF60 gene and provided a reference for delineation of the genotype-phenotype correlation of the VRJS.
关键词
Verheij综合征/PUF60基因/骨骼发育畸形/椎体融合
Key words
Verheij syndrome/PUF60 gene/Malformation of bone development/Vertebral fusion
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