講演情報
[O16-2]原因不明のSGA性低身長140名における (epi) geneticな要因の解明
○原 香織1, 中村 明枝1,2, 福家 智子1, 井上 毅信1, 川嶋 明香1, 松原 圭子1, 佐野 伸一朗1,3, 山澤 一樹1,4, 深見 真紀1, 緒方 勤1,5,6, 鏡 雅代1 (1.国立成育医療研究センター研究所 分子内分泌研究部, 2.北海道大学病院 小児科, 3.静岡県立こども病院 糖尿病代謝内科, 4.独立行政法人国立病院機構東京医療センター 臨床遺伝センター, 5.浜松医科大学 医化学講座, 6.浜松医療センター 小児科)
Backgrounds: Children born small-for-gestational-age with short stature (SGA-SS) is associated with (epi) genetic defects, including imprinting disorders (IDs), pathogenic copy number variants (PCNVs), and pathogenic sequence variants of genes involved in growth. However, comprehensive studies evaluating these three factors are very limited.
Objective: To clarify the contribution of IDs, PCNVs, and pathogenic sequence variants to SGA-SS.
Methods: We enrolled 140 patients of SGA-SS with unknown etiology. We conducted 1. clinical analysis using Netchine-Harbison clinical scoring system for detecting Silver-Russell syndrome (SRS), 2. methylation analysis for ten IDs-related differentially methylated regions, 3. copy number analysis using array comparative genomic hybridization, 4. multigene sequencing for 685 genes involved in growth.
Results: We identified 42 patients with SRS based on NH-CSS, four patients with IDs other than SRS, including Temple syndrome (n=2), Prader-Willi syndrome (n=1), and maternal uniparental disomy chromosome 6 (n=1), eight patients with PCNVs, and eleven patients with pathogenic sequence variants. We clarified the etiologies of 65 (46%) patients.
Discussion: This study is the largest comprehensive genetic analysis for SGA-SS and elucidated the etiology of about half of the patients. We demonstrated the clinical significance of comprehensive genetic analysis, including evaluation for IDs, in investigating the etiology of SGA-SS.
Conclusion: We clarified the etiology of about half of SGA-SS through the world’s largest comprehensive genetic analysis.
Objective: To clarify the contribution of IDs, PCNVs, and pathogenic sequence variants to SGA-SS.
Methods: We enrolled 140 patients of SGA-SS with unknown etiology. We conducted 1. clinical analysis using Netchine-Harbison clinical scoring system for detecting Silver-Russell syndrome (SRS), 2. methylation analysis for ten IDs-related differentially methylated regions, 3. copy number analysis using array comparative genomic hybridization, 4. multigene sequencing for 685 genes involved in growth.
Results: We identified 42 patients with SRS based on NH-CSS, four patients with IDs other than SRS, including Temple syndrome (n=2), Prader-Willi syndrome (n=1), and maternal uniparental disomy chromosome 6 (n=1), eight patients with PCNVs, and eleven patients with pathogenic sequence variants. We clarified the etiologies of 65 (46%) patients.
Discussion: This study is the largest comprehensive genetic analysis for SGA-SS and elucidated the etiology of about half of the patients. We demonstrated the clinical significance of comprehensive genetic analysis, including evaluation for IDs, in investigating the etiology of SGA-SS.
Conclusion: We clarified the etiology of about half of SGA-SS through the world’s largest comprehensive genetic analysis.