PURA syndrome: clinical delineation and genotype-phenotype study in 32 individuals with review of published literature.
PURA syndrome: clinical delineation and genotype-phenotype study in 32 individuals with review of published literature.
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DOI：
10.1136/jmedgenet-2017-104946
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发表时间：
2018-03
影响因子：
4
通讯作者：
Baralle D
中科院分区：
文献类型：
--
作者：
Reijnders MRF;Janowski R;Alvi M;Self JE;van Essen TJ;Vreeburg M;Rouhl RPW;Stevens SJC;Stegmann APA;Schieving J;Pfundt R;van Dijk K;Smeets E;Stumpel CTRM;Bok LA;Cobben JM;Engelen M;Mansour S;Whiteford M;Chandler KE;Douzgou S;Cooper NS;Tan EC;Foo R;Lai AHM;Rankin J;Green A;Lönnqvist T;Isohanni P;Williams S;Ruhoy I;Carvalho KS;Dowling JJ;Lev DL;Sterbova K;Lassuthova P;Neupauerová J;Waugh JL;Keros S;Clayton-Smith J;Smithson SF;Brunner HG;van Hoeckel C;Anderson M;Clowes VE;Siu VM;Ddd Study T;Selber P;Leventer RJ;Nellaker C;Niessing D;Hunt D;Baralle D
PURA 的从头突变最近被描述为导致 PURA 综合征，这是一种神经发育障碍，其特征是严重智力障碍 (ID)、癫痫、喂养困难和新生儿肌张力低下。描述 PURA 综合征的临床谱并研究基因型-表型相关性。对患有 ID 的个体进行了基于诊断或基于研究的外显子组或桑格测序。我们系统地收集了新确定的 PURA 综合征个体的临床和突变数据，评估了先前报告的个体的数据并对照片进行了计算分析。我们使用果蝇衍生的 Pur-alpha 同源物晶体结构的 3D 计算机模型根据预测效果对突变进行分类。最后，我们通过分析复发突变和突变类别来探索基因型-表型相关性。我们报告了 32 名个体的 PURA（富含嘌呤元素结合蛋白 A）突变，这是迄今为止描述的最大的群体。对包括之前发表的 22 例病例在内的临床数据进行评估后发现，所有病例均具有中度至重度智力障碍和新生儿发病症状，包括肌张力减退（96%）、呼吸问题（57%）、喂养困难（77%）、惊吓反应过度（44%）、嗜睡（66%）和体温过低（35%）。经常观察到癫痫（54%）、胃肠道（69%）、眼科（51%）和内分泌问题（42%）。面部照片的计算分析显示出微妙的面部畸形。通过将突变分组为功能类别，没有发现强的基因型-表型相关性。我们通过另外 32 名个体的鉴定描述了 PURA 综合征的临床谱。通过有针对性的桑格测序对一个人的识别表明了该综合征的临床可识别性。基因型-表型分析显示突变类别和疾病严重程度之间没有显着相关性。
De novo mutations in PURA have recently been described to cause PURA syndrome, a neurodevelopmental disorder characterised by severe intellectual disability (ID), epilepsy, feeding difficulties and neonatal hypotonia. To delineate the clinical spectrum of PURA syndrome and study genotype-phenotype correlations. Diagnostic or research-based exome or Sanger sequencing was performed in individuals with ID. We systematically collected clinical and mutation data on newly ascertained PURA syndrome individuals, evaluated data of previously reported individuals and performed a computational analysis of photographs. We classified mutations based on predicted effect using 3D in silico models of crystal structures of Drosophila-derived Pur-alpha homologues. Finally, we explored genotype-phenotype correlations by analysis of both recurrent mutations as well as mutation classes. We report mutations in PURA (purine-rich element binding protein A) in 32 individuals, the largest cohort described so far. Evaluation of clinical data, including 22 previously published cases, revealed that all have moderate to severe ID and neonatal-onset symptoms, including hypotonia (96%), respiratory problems (57%), feeding difficulties (77%), exaggerated startle response (44%), hypersomnolence (66%) and hypothermia (35%). Epilepsy (54%) and gastrointestinal (69%), ophthalmological (51%) and endocrine problems (42%) were observed frequently. Computational analysis of facial photographs showed subtle facial dysmorphism. No strong genotype-phenotype correlation was identified by subgrouping mutations into functional classes. We delineate the clinical spectrum of PURA syndrome with the identification of 32 additional individuals. The identification of one individual through targeted Sanger sequencing points towards the clinical recognisability of the syndrome. Genotype-phenotype analysis showed no significant correlation between mutation classes and disease severity.
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影响因子：
1.3
作者：
Bonaglia, Maria Clara;Zanotta, Nicoletta;Zucca, Claudio
通讯作者：
Zucca, Claudio
影响因子：
14.8
作者：
Kelley LA;Mezulis S;Yates CM;Wass MN;Sternberg MJ
通讯作者：
Sternberg MJ
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：
2
作者：
Brown, Natasha;Burgess, Trent;Stark, Zornitza
通讯作者：
Stark, Zornitza
影响因子：
7.2
作者：
Rezkalla, Joshua;Von Wald, Tiffany;Hansen, Keith A.
通讯作者：
Hansen, Keith A.