Molecular and clinical analyses of two patients with UPD(16)mat detected by screening 94 patients with Silver-Russell syndrome phenotype of unknown aetiology.
Molecular and clinical analyses of two patients with UPD(16)mat detected by screening 94 patients with Silver-Russell syndrome phenotype of unknown aetiology.
复制标题
DOI：
10.1136/jmedgenet-2018-105463
复制
发表时间：
2019-06
影响因子：
4
通讯作者：
Kagami M
中科院分区：
文献类型：
--
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
最近报道了1例16号染色体母系单亲二体(UPD(16)MAT)患者，表现为Silver-Russell综合征(SRS)表型。SRS的特点是生长失败和畸形特征。目的：阐明UPD(16)MAT在病因不明的SRS表型患者中的患病率，以及UPD(16)MAT与SRS的表型差异。我们对94例病因不明的SRS患者进行了研究。63例患者符合Netchine-Harbison临床评分系统(NH-CS)标准，其中25例同时存在额部突出和相对巨头畸形(临床SRS)。其余31名患者仅符合三项NH-CS标准，但临床怀疑为SRS。为了检测UPD(16)MAT，我们对16号染色体上的ZNF597：TSS-差异甲基化区域(DMR)进行了甲基化分析，随后对低甲基化的ZNF597：TSS-DMR患者进行了微卫星、SNP阵列和外显子组分析。在94例病因学未知的SRS表型患者中，我们确定了两名(2.1%)患有母体16号染色体等体和异体的患者。两名患者均表现为早产以及出生前和出生后发育不良。男患者合并室间隔缺损和尿路下裂。全外显子组测序未检测到与其表型相关的基因突变。我们建议在没有已知病因的SRS表型患者中考虑对UPD(16)MAT进行基因检测。
Recently, a patient with maternal uniparental disomy of chromosome 16 (UPD(16)mat) presenting with Silver-Russell syndrome (SRS) phenotype was reported. SRS is characterised by growth failure and dysmorphic features. To clarify the prevalence of UPD(16)mat in aetiology-unknown patients with SRS phenotype and phenotypic differences between UPD(16)mat and SRS. We studied 94 patients with SRS phenotype of unknown aetiology. Sixty-three satisfied the Netchine-Harbison clinical scoring system (NH-CSS) criteria, and 25 out of 63 patients showed both protruding forehead and relative macrocephaly (clinical SRS). The remaining 31 patients met only three NH-CSS criteria, but were clinically suspected as having SRS. To detect UPD(16)mat, we performed methylation analysis for the ZNF597:TSS-differentially methylated region (DMR) on chromosome 16 and subsequently performed microsatellite, SNP array and exome analyses in the patients with hypomethylated ZNF597:TSS-DMR. We identified two patients (2.1%) with a mixture of maternal isodisomy and heterodisomy of chromosome 16 in 94 aetiology-unknown patients with SRS phenotype. Both patients exhibited preterm birth and prenatal and postnatal growth failure. The male patient had ventricular septal defect and hypospadias. Whole-exome sequencing detected no gene mutations related to their phenotypes. We suggest considering genetic testing for UPD(16)mat in SRS phenotypic patients without known aetiology.
登录
查看更多内容
影响因子：
4.5
作者：
Helm BM;Willer JR;Sadeghpour A;Golzio C;Crouch E;Vergano SS;Katsanis N;Davis EE
通讯作者：
Davis EE
影响因子：
3.7
作者：
Fuke T;Mizuno S;Nagai T;Hasegawa T;Horikawa R;Miyoshi Y;Muroya K;Kondoh T;Numakura C;Sato S;Nakabayashi K;Tayama C;Hata K;Sano S;Matsubara K;Kagami M;Yamazawa K;Ogata T
通讯作者：
Ogata T
影响因子：
--
作者：
Sachwitz, Jana;Strobl-Wildemann, Getrud;Eggermann, Thomas
通讯作者：
Eggermann, Thomas
DOI：
10.1038/ejhg.2014.234
发表时间：
2015-08
期刊：
European journal of human genetics : EJHG
影响因子：
--
作者：
Kagami M;Mizuno S;Matsubara K;Nakabayashi K;Sano S;Fuke T;Fukami M;Ogata T
通讯作者：
Ogata T
影响因子：
2
作者：
Ghanim, Mustafa;Rossignol, Sylvie;Vincent-Delorme, Catherine
通讯作者：
Vincent-Delorme, Catherine