Loss of imprinting of the human-specific imprinted gene ZNF597 causes prenatal growth retardation and dysmorphic features: implications for phenotypic overlap with Silver-Russell syndrome.
Loss of imprinting of the human-specific imprinted gene ZNF597 causes prenatal growth retardation and dysmorphic features: implications for phenotypic overlap with Silver-Russell syndrome.
复制标题
人类特异性印记基因ZNF597的印记丢失会导致产前发育迟缓和畸形特征：与Silver-Russell综合征表型重叠的含义。
DOI：
10.1136/jmedgenet-2020-107019
复制
发表时间：
2021-06
影响因子：
4
通讯作者：
Kagami M
中科院分区：
文献类型：
--
作者：
Yamazawa K;Inoue T;Sakemi Y;Nakashima T;Yamashita H;Khono K;Fujita H;Enomoto K;Nakabayashi K;Hata K;Nakashima M;Matsunaga T;Nakamura A;Matsubara K;Ogata T;Kagami M
ZNF597 编码锌指蛋白，是人类特异性母体表达的印记基因，位于 16p13.3。 ZNF597的亲本表达受ZNF597:TSS-DMR调节，其中只有父本等位基因在植入后时期获得甲基化。 ZNF597 的过度表达可能导致一些与母体单亲二倍体 16 号染色体 (UPD(16)mat) 相关的表型，最近报道了一些 UPD(16)mat 患者出现 Silver-Russell 综合征 (SRS) 表型。一名 6 岁男孩出现产前生长受限、出生时巨头畸形、婴儿期前额突出和无名指弯曲。进行甲基化、表达、微卫星标记、单核苷酸多态性阵列和三重外显子组测序分析。在患者中证实了 ZNF597:TSS-DMR 的孤立性低甲基化以及随后的 ZNF597 印记丢失和过度表达。表观遗传改变，例如 UPD，包括 UPD(16)mat 和其他甲基化缺陷，被排除在外。尚未鉴定出影响其表型的致病序列或拷贝数变异，表明初次表突变发生在合子后。我们报告了第一例孤立的 ZNF597 印记缺陷，尽管不满足临床 SRS 标准，但显示出与 SRS 的表型重叠。可以推测涉及 ZNF597 印迹结构域的新型印记障碍实体。
ZNF597, encoding a zinc-finger protein, is the human-specific maternally expressed imprinted gene located on 16p13.3. The parent-of-origin expression of ZNF597 is regulated by the ZNF597:TSS-DMR, of which only the paternal allele acquires methylation during postimplantation period. Overexpression of ZNF597 may contribute to some of the phenotypes associated with maternal uniparental disomy of chromosome 16 (UPD(16)mat), and some patients with UPD(16)mat presenting with Silver-Russell syndrome (SRS) phenotype have recently been reported. A 6-year-old boy presented with prenatal growth restriction, macrocephaly at birth, forehead protrusion in infancy and clinodactyly of the fifth finger. Methylation, expression, microsatellite marker, single nucleotide polymorphism array and trio whole-exome sequencing analyses were conducted. Isolated hypomethylation of the ZNF597:TSS-DMR and subsequent loss of imprinting and overexpression of ZNF597 were confirmed in the patient. Epigenetic alterations, such as UPD including UPD(16)mat and other methylation defects, were excluded. Pathogenic sequence or copy number variants affecting his phenotypes were not identified, indicating that primary epimutation occurred postzygotically. We report the first case of isolated ZNF597 imprinting defect, showing phenotypic overlap with SRS despite not satisfying the clinical SRS criteria. A novel imprinting disorder entity involving the ZNF597 imprinted domain can be speculated.
登录
查看更多内容
影响因子：
4.5
作者：
Van Damme P;Hole K;Pimenta-Marques A;Helsens K;Vandekerckhove J;Martinho RG;Gevaert K;Arnesen T
通讯作者：
Arnesen T
影响因子：
4
作者：
Inoue T;Yagasaki H;Nishioka J;Nakamura A;Matsubara K;Narumi S;Nakabayashi K;Yamazawa K;Fuke T;Oka A;Ogata T;Fukami M;Kagami M
通讯作者：
Kagami M
早期人类发育过程中DNA甲基化动力学的全基因组分析。
影响因子：
4.5
作者：
Okae H;Chiba H;Hiura H;Hamada H;Sato A;Utsunomiya T;Kikuchi H;Yoshida H;Tanaka A;Suyama M;Arima T
通讯作者：
Arima T
影响因子：
7
作者：
Baran Y;Subramaniam M;Biton A;Tukiainen T;Tsang EK;Rivas MA;Pirinen M;Gutierrez-Arcelus M;Smith KS;Kukurba KR;Zhang R;Eng C;Torgerson DG;Urbanek C;GTEx Consortium;Li JB;Rodriguez-Santana JR;Burchard EG;Seibold MA;MacArthur DG;Montgomery SB;Zaitlen NA;Lappalainen T
通讯作者：
Lappalainen T
影响因子：
7
作者：
Court F;Tayama C;Romanelli V;Martin-Trujillo A;Iglesias-Platas I;Okamura K;Sugahara N;Simón C;Moore H;Harness JV;Keirstead H;Sanchez-Mut JV;Kaneki E;Lapunzina P;Soejima H;Wake N;Esteller M;Ogata T;Hata K;Nakabayashi K;Monk D
通讯作者：
Monk D