Clinical and molecular consequences of disease-associated de novo mutations in SATB2.
Clinical and molecular consequences of disease-associated de novo mutations in SATB2.
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DOI：
10.1038/gim.2016.211
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发表时间：
2017-08
期刊：
影响因子：
--
通讯作者：
FitzPatrick DR
中科院分区：
文献类型：
--
作者：
Bengani H;Handley M;Alvi M;Ibitoye R;Lees M;Lynch SA;Lam W;Fannemel M;Nordgren A;Malmgren H;Kvarnung M;Mehta S;McKee S;Whiteford M;Stewart F;Connell F;Clayton-Smith J;Mansour S;Mohammed S;Fryer A;Morton J;UK10K Consortium;Grozeva D;Asam T;Moore D;Sifrim A;McRae J;Hurles ME;Firth HV;Raymond FL;Kini U;Nellåker C;Ddd Study;FitzPatrick DR
在智力残疾的基础上确定的个体中，表征与影响SATB 2功能的新生突变相关的特征。研究了20个先前未报道的具有19种不同SATB 2突变（11种功能丧失和8种错义变体）的个体。成纤维细胞用于测量突变蛋白质产生。使用荧光标记的蛋白质评估野生型和突变体SATB 2的亚细胞定位和移动性。复发的临床特征包括神经发育障碍（19/19）、言语缺失/近乎缺失（16/19）、正常躯体生长（17/19）、腭裂（9/19）、流口水（12/19）和牙齿异常（8/19）。八个错义变体中有六个聚集在第一个CUT结构域中。在一个家族中，由于性腺镶嵌而出现同胞复发。最后一个外显子中的无义突变导致产生保留所有三个DNA结合结构域的截短蛋白。SATB 2核迁移率是突变依赖性的; CUT 1中的p.Arg389Cys增加迁移率，CUT 2中的p.Gly515Ser和CUT 2和HOX之间的p.Gln566Lys降低迁移率。错义变异个体的临床特征与功能丧失个体的临床特征难以区分。SATB 2单倍不足是综合征性智力残疾的常见原因。当产生突变SATB 2蛋白时，该蛋白表现出功能失活，具有染色质或基质缔合的破坏模式。Genet Med advance online publication 2017年2月2日
To characterize features associated with de novo mutations affecting SATB2 function in individuals ascertained on the basis of intellectual disability. Twenty previously unreported individuals with 19 different SATB2 mutations (11 loss-of-function and 8 missense variants) were studied. Fibroblasts were used to measure mutant protein production. Subcellular localization and mobility of wild-type and mutant SATB2 were assessed using fluorescently tagged protein. Recurrent clinical features included neurodevelopmental impairment (19/19), absent/near absent speech (16/19), normal somatic growth (17/19), cleft palate (9/19), drooling (12/19), and dental anomalies (8/19). Six of eight missense variants clustered in the first CUT domain. Sibling recurrence due to gonadal mosaicism was seen in one family. A nonsense mutation in the last exon resulted in production of a truncated protein retaining all three DNA-binding domains. SATB2 nuclear mobility was mutation-dependent; p.Arg389Cys in CUT1 increased mobility and both p.Gly515Ser in CUT2 and p.Gln566Lys between CUT2 and HOX reduced mobility. The clinical features in individuals with missense variants were indistinguishable from those with loss of function. SATB2 haploinsufficiency is a common cause of syndromic intellectual disability. When mutant SATB2 protein is produced, the protein appears functionally inactive with a disrupted pattern of chromatin or matrix association. Genet Med advance online publication 02 February 2017
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影响因子：
3.7
作者：
Rosenfeld JA;Ballif BC;Lucas A;Spence EJ;Powell C;Aylsworth AS;Torchia BA;Shaffer LG
通讯作者：
Shaffer LG
影响因子：
4
作者：
Ansari M;Poke G;Ferry Q;Williamson K;Aldridge R;Meynert AM;Bengani H;Chan CY;Kayserili H;Avci S;Hennekam RC;Lampe AK;Redeker E;Homfray T;Ross A;Falkenberg Smeland M;Mansour S;Parker MJ;Cook JA;Splitt M;Fisher RB;Fryer A;Magee AC;Wilkie A;Barnicoat A;Brady AF;Cooper NS;Mercer C;Deshpande C;Bennett CP;Pilz DT;Ruddy D;Cilliers D;Johnson DS;Josifova D;Rosser E;Thompson EM;Wakeling E;Kinning E;Stewart F;Flinter F;Girisha KM;Cox H;Firth HV;Kingston H;Wee JS;Hurst JA;Clayton-Smith J;Tolmie J;Vogt J;Tatton-Brown K;Chandler K;Prescott K;Wilson L;Behnam M;McEntagart M;Davidson R;Lynch SA;Sisodiya S;Mehta SG;McKee SA;Mohammed S;Holden S;Park SM;Holder SE;Harrison V;McConnell V;Lam WK;Green AJ;Donnai D;Bitner-Glindzicz M;Donnelly DE;Nellåker C;Taylor MS;FitzPatrick DR
通讯作者：
FitzPatrick DR
影响因子：
5.2
作者：
Doecker, Dennis;Schubach, Max;Bartholdi, Deborah
通讯作者：
Bartholdi, Deborah
DOI：
10.1002/jez.b.21205
发表时间：
2008-06-15
影响因子：
2.2
作者：
Depew, Michael J.;Compagnucci, Claudia
通讯作者：
Compagnucci, Claudia
影响因子：
2
作者：
Lieden, Agne;Kvarnung, Malin;Lundberg, Elisabeth Syk
通讯作者：
Lundberg, Elisabeth Syk