Abstract：
Verheij syndrome (VRJS) is a rare microdeletion syndrome of chromosome 8q24.3 that is characterized by severe growth retardation, microcephaly, vertebral anomalies, joint laxity/dislocation, psychomotor retardation, cardiac and renal defects, and dysmorphic facial features. Pathogenic variants of PUF60 (Poly-U Binding Splicing Factor 60 kDa) have been found to cause VRJS. Here we present a Turkish patient with Verheij syndrome who has typical facial dysmorphic features and renal and cardiac abnormalities, scoliosis, tethered cord, and mild intellectual disability.
This is a case report of a 11-year-old female child who presented with Verheij syndrome. Blood samples were collected from the patient and the family. We performed whole exome sequencing was used to identify potential genetic mutations. We also used 3-dimensional protein structure analysis to identify the effect of the mutation.
A de-novo in-frame variant (c.449_457delCAAAGGGGG; p.Ala150_Phe152del) of the PUF60 gene was identified by whole exome sequencing. According to ACMG guidelines in 2015, the mutation is classified as pathogenic and it has been reported in the clinvar database. Results of in-silico prediction software tools predicted the mutation was pathogenic. Protein structure analysis showed that the three residues affected by the in-frame deletion form could lead to impaired stability and function of the PUF60 protein.
To date, 25 patients have been reported with PUF60 mutations in the medical literature. In this article, we report a patient with VRJS who had the unusual findings of tethered cord syndrome and renal abnormalities. As far as we know, this is the first patient from Turkey who has been diagnosed with Verheij syndrome.
This is a case report of a 11-year-old female child who presented with Verheij syndrome. Blood samples were collected from the patient and the family. We performed whole exome sequencing was used to identify potential genetic mutations. We also used 3-dimensional protein structure analysis to identify the effect of the mutation.
A de-novo in-frame variant (c.449_457delCAAAGGGGG; p.Ala150_Phe152del) of the PUF60 gene was identified by whole exome sequencing. According to ACMG guidelines in 2015, the mutation is classified as pathogenic and it has been reported in the clinvar database. Results of in-silico prediction software tools predicted the mutation was pathogenic. Protein structure analysis showed that the three residues affected by the in-frame deletion form could lead to impaired stability and function of the PUF60 protein.
To date, 25 patients have been reported with PUF60 mutations in the medical literature. In this article, we report a patient with VRJS who had the unusual findings of tethered cord syndrome and renal abnormalities. As far as we know, this is the first patient from Turkey who has been diagnosed with Verheij syndrome.
摘要：
未经证实：Verheij综合征（VRJS）是一种罕见的染色体8q24.3微缺失综合征，其特征是严重的生长迟缓，小头畸形,椎骨异常,关节松弛/脱位,精神运动性迟钝,心脏和肾脏缺陷，和畸形的面部特征。已经发现PUF60(聚-U结合剪接因子60kDa)的致病变体引起VRJS。在这里，我们介绍了一名患有Verheij综合征的土耳其患者，他具有典型的面部畸形特征以及肾脏和心脏异常，脊柱侧弯,系绳,轻度智力残疾。
未经证实：这是一例11岁女性儿童出现Verheij综合征的病例报告。从患者和家属收集血样。我们使用全外显子组测序来鉴定潜在的基因突变。我们还使用3维蛋白质结构分析来鉴定突变的影响。
UNASSIGNED：通过全外显子测序鉴定了PUF60基因的从头框内变体（c.449_457delCAAAGGGGG；p.Ala150_Phe152del）。根据2015年ACMG指南，该突变被归类为致病性突变，并已在clinvar数据库中报告。计算机预测软件工具的结果预测该突变是致病性的。蛋白质结构分析表明，受框内缺失形式影响的三个残基可能导致PUF60蛋白的稳定性和功能受损。
未经批准：迄今为止，在医学文献中已经报道了25例具有PUF60突变的患者。在这篇文章中,我们报告了1例VRJS患者,发现脊髓栓系综合征和肾脏异常.据我们所知,这是土耳其首例确诊为Verheij综合征的患者.
未经证实：这是一例11岁女性儿童出现Verheij综合征的病例报告。从患者和家属收集血样。我们使用全外显子组测序来鉴定潜在的基因突变。我们还使用3维蛋白质结构分析来鉴定突变的影响。
UNASSIGNED：通过全外显子测序鉴定了PUF60基因的从头框内变体（c.449_457delCAAAGGGGG；p.Ala150_Phe152del）。根据2015年ACMG指南，该突变被归类为致病性突变，并已在clinvar数据库中报告。计算机预测软件工具的结果预测该突变是致病性的。蛋白质结构分析表明，受框内缺失形式影响的三个残基可能导致PUF60蛋白的稳定性和功能受损。
未经批准：迄今为止，在医学文献中已经报道了25例具有PUF60突变的患者。在这篇文章中,我们报告了1例VRJS患者,发现脊髓栓系综合征和肾脏异常.据我们所知,这是土耳其首例确诊为Verheij综合征的患者.
