Frequency and clinical characteristics of distinct etiologies in patients with Silver-Russell syndrome diagnosed based on the Netchine-Harbison clinical scoring system
Frequency and clinical characteristics of distinct etiologies in patients with Silver-Russell syndrome diagnosed based on the Netchine-Harbison clinical scoring system
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DOI：
10.1038/s10038-022-01048-7
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发表时间：
2022-05-24
影响因子：
3.5
通讯作者：
Kagami, Masayo
中科院分区：
文献类型：
--
作者：
Fuke, Tomoko;Nakamura, Akie;Kagami, Masayo
Silver-Russel综合征（SRS）是一种典型的以生长障碍为特征的印迹障碍（ID），其临床特征可作为诊断依据。最近，国际共识建议使用Netchine-Harbison临床评分系统（NH-CSS）作为临床诊断标准。H19/IGF 2甲基化缺失：基因间差异甲基化区域（H19 LOM）和母体单亲二体性7号染色体（UPD（7）mat）是SRS的常见病因;然而，在符合NH-CSS的患者中报告了其他ID、致病性基因变异（PV）和致病性拷贝数变异（PCNV）。为了阐明每种病因的频率和临床特征，我们对173例符合NH-CSS的患者进行了（epi）遗传分析。H19 L0 M和UPD（7）的检出率为34.1%。PCNV、其他ID和PV占15.0%。所有6项NH-CSS的患者最常观察到H19 LOM和UPD（7）mat。本研究证实了NH-CSS作为临床诊断标准的适用性，SRS的（epi）遗传异质性，并表明有必要进一步讨论“SRS谱”。
Silver-Russel syndrome (SRS) is a representative imprinting disorder (ID) characterized by growth failure and diagnosed by clinical features. Recently, international consensus has recommended using the Netchine-Harbison clinical scoring system (NH-CSS) as clinical diagnostic criteria. Loss of methylation of H19/IGF2:intergenic differentially methylated region (H19LOM) and maternal uniparental disomy chromosome 7 (UPD(7)mat) are common etiologies of SRS; however, other IDs, pathogenic variants (PVs) of genes, and pathogenic copy number variants (PCNVs) have been reported in patients meeting NH-CSS. To clarify the frequency and clinical characteristics of each etiology, we conducted (epi)genetic analysis in 173 patients satisfying NH-CSS. H19LOM and UPD(7)mat were identified in 34.1%. PCNVs, other IDs, and PVs were in 15.0%. Patients with all six NH-CSS items were most frequently observed with H19LOM and UPD(7)mat. This study confirmed the suitability of NH-CSS as clinical diagnostic criteria, the (epi)genetic heterogeneity of SRS, and showed the necessity of further discussion regarding the "SRS spectrum".