Deletions and epimutations affecting the human 14q32.2 imprinted region in individuals with paternal and maternal upd(14)-like phenotypes

被引：245

作者：

Kagami, Masayo ^{[2
]}

Sekita, Yoichi ^{[1
]}

Nishimura, Gen ^{[3
]}

Irie, Masahito ^{[1
]}

Kato, Fumiko ^{[2
]}

Okada, Michiyo ^{[2
]}

Yamamori, Shunji ^{[4
]}

Kishimoto, Hiroshi ^{[5
]}

Nakayama, Masahiro ^{[6
]}

Tanaka, Yukichi ^{[7
]}

Matsuoka, Kentarou ^{[8
]}

Takahashi, Tsutomu ^{[9
]}

Noguchi, Mika ^{[10
]}

Tanaka, Yoko ^{[11
]}

Masumoto, Kouji

Utsunomiya, Takeshi ^{[12
,19
]}

Kouzan, Hiroko ^{[13
]}

Komatsu, Yumiko ^{[14
]}

Ohashi, Hirofumi ^{[15
]}

Kurosawa, Kenji ^{[16
]}

Kosaki, Kenjirou ^{[17
]}

Ferguson-Smith, Anne C. ^{[18
]}

Ishino, Fumitoshi ^{[1
]}

Ogata, Tsutomu ^{[2
]}

机构：

[1] Tokyo Med & Dent Univ, Med Res Inst, Dept Epigenet, Tokyo 1010062, Japan

[2] Nat Res Inst Child Hlth & Dev, Dept Endocrinol & Metab, Tokyo 1578535, Japan

[3] Tokyo Metropolitan Kiyose Childrens Hosp, Dept Radiol, Tokyo 2048567, Japan

[4] Mitsubishi Chem Medience Corp, Tokyo 1748555, Japan

[5] Saitama Childrens Med Ctr, Div Pathol, Kawagoe, Saitama 3398551, Japan

[6] Osaka Med Ctr & Res Inst Maternal & Child Hlth, Div Pathol, Osaka 5941101, Japan

[7] Kanagawa Childrens Med Ctr, Div Pathol, Yokohama, Kanagawa 2328555, Japan

[8] Natl Ctr Child Hlth & Dev, Div Pathol, Tokyo 1578535, Japan

[9] Akita Univ, Sch Med, Dept Pediat, Akita 0108543, Japan

[10] Chiba Kaihin Municipal Hosp, Dept Neonatol, Chiba 2610012, Japan

[11] Tokyo Dent Coll Ichikawa Gen Hosp, Dept Pediat, Ichikawa 2728513, Japan

[12] Kyushu Univ, Sch Med, Dept Pediat Surg, Fukuoka 8128582, Japan

[13] Takamatsu Red Cross Hosp, Dept Pediat, Takamatsu, Kagawa 7600017, Japan

[14] Numazu City Hosp, Dept Pediat, Numazu 4100302, Japan

[15] Saitama Childrens Med Ctr, Div Med Genet, Kawagoe, Saitama 3398551, Japan

[16] Kanagawa Childrens Med Ctr, Div Med Genet, Yokohama, Kanagawa 2328555, Japan

[17] Keio Univ, Sch Med, Dept Pediat, Tokyo 1608582, Japan

[18] Univ Cambridge, Dept Physiol Dev & Neurosci, Cambridge CB2 3EG, England

[19] Kagoshima City Hosp, Dept Neonatol, Kagoshima 8928580, Japan

来源：

NATURE GENETICS | 2008年 / 40卷 / 02期

基金：

英国医学研究理事会;

关键词：

D O I：

10.1038/ng.2007.56

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Human chromosome 14q32.2 carries a cluster of imprinted genes including paternally expressed genes (PEGs) such as DLK1 and RTL1 and maternally expressed genes (MEGs) such as MEG3 (also known as GTL2), RTL1as (RTL1 antisense) and MEG8 (refs. 1,2), together with the intergenic differentially methylated region (IG-DMR) and the MEG3-DMR3-5. Consistent with this, paternal and maternal uniparental disomy for chromosome 14 (upd(14) pat and upd(14) mat) cause distinct phenotypes(6,7). We studied eight individuals (cases 1-8) with a upd(14) pat-like phenotype and three individuals (cases 9-11) with a upd(14) mat-like phenotype in the absence of upd(14) and identified various deletions and epimutations affecting the imprinted region. The results, together with recent mouse data(4,8-10), imply that the IG-DMR has an important cis-acting regulatory function on the maternally inherited chromosome and that excessive RTL1 expression and decreased DLK1 and RTL1 expression are relevant to upd(14) pat-like and upd(14) mat-like phenotypes, respectively.

引用

页码：237 / 242

页数：6

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