PUF60基因变异致Verheij综合征一例并文献复习

PUF60 Gene Mutation Caused Verheij Syndrome in a Case and Literature Review

摘要: 目的：总结PUF60基因变异致Verheij综合征的临床表型及遗传学特点。方法：回顾性分析青岛市妇女儿童医院2019年8月接诊的1例PUF60基因变异致Verheij综合征患儿的临床资料及分子遗传学检测结果，并以“PUF60”、“PUF60基因”、“Verheij综合征”、“Verheij syndrome”为检索词，分别在中国知网、万方数据知识服务平台、PubMed以及人类基因组突变数据库检索截至2020年8月的相关文献，总结PUF60基因变异患者的临床表型及基因型。结果：患儿女，10岁2月，以“自幼生长缓慢”就诊。同时合并智力障碍、特殊面容、心脏、眼组织、脊柱及手部等多系统畸形。患儿身高121.1 cm (<−3SD)，体重29.1 kg。生长激素激发试验提示生长激素部分缺乏(峰值8.93 ug/ml)，胰岛素样生长因子1 (Insulin-like growth factor 1, IGF-1) 188 ug/L，染色体示46，XX；骨龄相当于9.5岁；垂体CT平扫示蝶鞍未见明显扩大，鞍内结构显示不清；脊柱正位片示以胸12为中心略向右凸侧弯。全外显子高通量测序发现，患儿存在PUF60基因杂合变异(c.407_410delTCTA)，该变异可导致移码突变，在正常参考人群基因数据库中无相关频率报道，经父母样本验证，父母该位点均无变异，为新发变异。依据美国医学遗传学与基因学组学学会变异分类指南，该变异为致病性变异，该变异曾有报道。结论：Verheij综合征的临床表现包括精神运动发育迟滞、特殊的面部特征、心脏、肾脏、眼组织、脊柱及手足等多系统畸形。PUF60基因c.407_410delTCTA变异为该患儿的致病原因。基因检测有助于该病早期诊断。

Abstract: Object: To summarize the clinical phenotypes and genetic characteristics of Verheij syndrome caused by PUF60 gene variation. Methods: The clinical data and molecular genetic test results of a child with Verheij syndrome caused by PUF60 gene mutation in Qingdao Women’s and Children’s Hospital in August 2019 were retrospectively analyzed. The relevant literatures up to August 2020 were searched on China knowledge Network, Wanfang data knowledge Service platform, PubMed and Human Genome mutation Database with the search term of “PUF60”, “PUF60 gene”, “Verheij syndrome” and “Verheij syndrome” respectively. The clinical phenotype and genotype of patients with PUF60 gene mutation were summarized. Results: The patient was 10 years old and 2 months old with “slow growth since childhood”, at the same time, mental retardation, special facial features, heart, eye tissue, spine and hand and other system deformities. The child was 121.1 cm in height (<−3SD) and 29.1 kg in weight. Growth hormone stimulation test showed partial growth hormone deficiency (peak value 8.93 ug/ml), insulin-like growth factor 1 (IGF-1) 188 ug/L, chromosome 46, XX; bone age was equivalent to 9.5 years; pituitary CT plain scan showed no obvious enlargement of sella, and the structure of sella was unclear. Anteroposterior radiograph of the spine showed a slight right convex curve centered on chest 12. High-throughput sequencing of the whole exon revealed that there was a heterozygous mutation of PUF60 gene (c.407_410DELTCTA) in the child, which could lead to frame-coding mutation, and no relevant frequency was reported in the normal reference population gene database. As verified by the parents’ samples, there was no mutation at this site in both parents, which was a new mutation. According to the American Society of Medical Genetics and Genomics Variation Classification Guidelines, this variant is pathogenic and has been reported before. Conclusion: The clinical manifestations of Verheij syndrome include psychomotor retardation, special facial features, and multi-system deformities of heart, kidney, eye tissue, spine, and hand and foot. The mutation of PUF60 gene c.407_410DELTCTA was the pathogenic cause of this child. Genetic testing can help diagnose the disease early.