PDF(Pubmed)
Abstract：
BACKGROUND: Silver-Russel syndrome (SRS) is a congenital disorder which is mainly characterized by intrauterine and postnatal growth retardation, relative macrocephaly, and characteristic (facial) dysmorphisms. The majority of patients shows a hypomethylation of the imprinting center region 1 (IC1) in 11p15 and maternal uniparental disomy of chromosome 7 (upd(7)mat), but in addition a broad spectrum of copy number variations (CNVs) and monogenetic variants (SNVs) has been reported in this cohort. These heterogeneous findings reflect the clinical overlap of SRS with other congenital disorders, but some of the CNVs are recurrent and have therefore been suggested as SRS-associated loci. However, this molecular heterogeneity makes the decision on the diagnostic workup of patients with SRS features challenging.
METHODS: A girl with clinical features of SRS but negatively tested for the IC1 hypomethylation and upd(7)mat was analyzed by whole genome sequencing in order to address both CNVs and SNVs in the same run. We identified a 11p13 microduplication affecting a region overlapping with a variant reported in a previously published patient with clinical features of Silver-Russel syndrome.
CONCLUSIONS: The identification of a 11p13 microduplication in a patient with SRS features confirms the considerable contribution of CNVs to SRS-related phenotypes, and it strengthens the evidence for a 11p13 microduplication syndrome as a differential diagnosis SRS. Furthermore, we could confirm that WGS is a valuable diagnostic tool in patients with SRS and related disorders, as it allows CNVs and SNV detection in the same run, thereby avoiding a time-consuming diagnostic testing process.
METHODS: A girl with clinical features of SRS but negatively tested for the IC1 hypomethylation and upd(7)mat was analyzed by whole genome sequencing in order to address both CNVs and SNVs in the same run. We identified a 11p13 microduplication affecting a region overlapping with a variant reported in a previously published patient with clinical features of Silver-Russel syndrome.
CONCLUSIONS: The identification of a 11p13 microduplication in a patient with SRS features confirms the considerable contribution of CNVs to SRS-related phenotypes, and it strengthens the evidence for a 11p13 microduplication syndrome as a differential diagnosis SRS. Furthermore, we could confirm that WGS is a valuable diagnostic tool in patients with SRS and related disorders, as it allows CNVs and SNV detection in the same run, thereby avoiding a time-consuming diagnostic testing process.
摘要：
背景：Silver-Russel综合征（SRS）是一种先天性疾病，主要表现为宫内和出生后发育迟缓，相对大头畸形，和特征性(面部)畸形。大多数患者在11p15中显示印记中心区域1（IC1）的低甲基化和7号染色体的母体单亲二体性（upd（7）mat），但此外,该队列中还报道了广泛的拷贝数变异(CNVs)和单基因变异(SNVs).这些异质性发现反映了SRS与其他先天性疾病的临床重叠，但一些CNVs是复发性的,因此被认为是SRS相关位点.然而,这种分子异质性使得对具有SRS特征的患者进行诊断检查的决策具有挑战性.
方法：通过全基因组测序分析了具有SRS临床特征但对IC1低甲基化和upd（7）mat进行阴性测试的女孩，以解决相同运行中的CNV和SNV。我们确定了11p13微重复，该重复影响了先前发表的具有Silver-Russel综合征临床特征的患者中报道的与变体重叠的区域。
结论：在具有SRS特征的患者中发现11p13微重复证实了CNVs对SRS相关表型的重要贡献，它加强了11p13微重复综合征作为鉴别诊断SRS的证据。此外，我们可以确认WGS是SRS和相关疾病患者的有价值的诊断工具，因为它允许在同一运行中检测CNV和SNV，从而避免了耗时的诊断测试过程。
方法：通过全基因组测序分析了具有SRS临床特征但对IC1低甲基化和upd（7）mat进行阴性测试的女孩，以解决相同运行中的CNV和SNV。我们确定了11p13微重复，该重复影响了先前发表的具有Silver-Russel综合征临床特征的患者中报道的与变体重叠的区域。
结论：在具有SRS特征的患者中发现11p13微重复证实了CNVs对SRS相关表型的重要贡献，它加强了11p13微重复综合征作为鉴别诊断SRS的证据。此外，我们可以确认WGS是SRS和相关疾病患者的有价值的诊断工具，因为它允许在同一运行中检测CNV和SNV，从而避免了耗时的诊断测试过程。
