Epigenotype-phenotype analysis of Silver-Russell syndrome pathogenesis mechanism

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K21051
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics; Embryonic/Neonatal medicine
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: Kato Fumiko 浜松医科大学, 医学部, 特任研究員 (10462798)
• Research Collaborator: OGATA Tsutomu 浜松医科大学, 医学部, 教授 (40169173) ; FUKAMI Maki 国立成育医療研究センター研究所, 分子内分泌研究部, 部長 (40265872) ; KAGAMI Masayo 国立成育医療研究センター研究所, 分子内分泌研究部, 室長 (70399484) ; SAWAKI Hamako 浜松医科大学, 医学部, 秘書 ; TAKEDA Yuriko 浜松医科大学, 医学部, 秘書
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: シルバーラッセル症候群(SRS) / 胎盤低形成 / 成長障害 / インプリンティング疾患 / エピ変異 / 第11番染色体 / ICR1(H19DMR) / ICR2(KvDMR)

Outline of Final Research Achievements

Silver-Russell syndrome (SRS) is a congenital developmental disorder characterized by pre- and postnatal growth failure, relative macrocephaly, triangular face, hemihypotrophy, and fifth finger clinodactly. SRS have a two major pathogenic factors. Previous studies have shown that epimutation(hypomethylation) of the paternally derived differentially methylated region(DMR) in the upstem of imprinting control region 1 (ICR1) located on the chr.11p15.5 and maternal uniparental disomy chr.7(upd(7)mat) account for around 45% and 5-10% of SRS patients, respectively. We performed methylation analysis for the of the 11p15 loci by pyrosequencing. As a result the SRS patients hypomethylations of ICR1 and was able to the definitive diagnosis. It is a study intended to elucidation of the disease establishment mechanism, the application to a clinical evaluation, improvement of the genetic counseling from the analysis of the SRS patient.

Free Research Field

分子遺伝学