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- Title
IGF2 Mutations.
- Authors
Masunaga, Yohei; Inoue, Takanobu; Yamoto, Kaori; Fujisawa, Yasuko; Sato, Yasuhiro; Kawashima-Sonoyama, Yuki; Morisada, Naoya; Iijima, Kazumoto; Ohata, Yasuhisa; Namba, Noriyuki; Suzumura, Hiroshi; Kuribayashi, Ryota; Yamaguchi, Yu; Yoshihashi, Hiroshi; Fukami, Maki; Saitsu, Hirotomo; Kagami, Masayo; Ogata, Tsutomu
- Abstract
<bold>Objective: </bold>IGF2 is a paternally expressed growth-promoting gene. Here, we report five cases with IGF2 mutations and review IGF2 mutation-positive patients described in the literature. We also compare clinical features between patients with IGF2 mutations and those with H19/IGF2:IG-DMR epimutations.<bold>Results: </bold>We recruited five cases with IGF2 mutations: case 1 with a splice site mutation (c.-6-1G>C) leading to skipping of exon 2 and cases 2-5 with different missense mutations (p.(Cys70Tyr), p.(Cys71Arg), p.(Cys33Ser), and p.(Cys45Ser)) affecting cysteine residues involved in the S-S bindings. All the mutations resided on the paternally inherited allele, and the mutation of case 5 was present in a mosaic condition. Clinical assessment revealed Silver-Russell syndrome (SRS) phenotype with Netchine-Harbison scores of ≥5/6 in all the apparently nonmosaic 14 patients with IGF2 mutations (cases 1-4 described in this study and 10 patients reported in the literature). Furthermore, compared with H19/IGF2:IG-DMR epimutations, IGF2 mutations were associated with low frequency of hemihypoplasia, high frequency of feeding difficulty and/or reduced body mass index, and mild degree of relative macrocephaly, together with occasional development of severe limb malformations, high frequency of cardiovascular anomalies and developmental delay, and low serum IGF-II values.<bold>Conclusions: </bold>This study indicates that IGF2 mutations constitute a rare but important cause of SRS. Furthermore, while both IGF2 mutations and H19/IGF2:IG-DMR epimutations lead to SRS, a certain degree of phenotypic difference is observed between the two groups, probably due to the different IGF2 expression pattern in target tissues.
- Subjects
BODY mass index; MISSENSE mutation; CARDIOVASCULAR diseases risk factors; DEVELOPMENTAL delay; CARDIOVASCULAR development
- Publication
Journal of Clinical Endocrinology & Metabolism, 2019, pN.PAG
- ISSN
0021-972X
- Publication type
journal article
- DOI
10.1210/clinem/dgz034