A biallelic SNIP1 Amish founder variant causes a recognizable neurodevelopmental disorder.
A biallelic SNIP1 Amish founder variant causes a recognizable neurodevelopmental disorder.
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阿米什人的双等位基因SNIP1创始人变异会导致一种可识别的神经发育障碍。
DOI：
10.1371/journal.pgen.1009803
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发表时间：
2021-09
期刊：
影响因子：
4.5
通讯作者：
Crosby AH
中科院分区：
文献类型：
--
作者：
Ammous Z;Rawlins LE;Jones H;Leslie JS;Wenger O;Scott E;Deline J;Herr T;Evans R;Scheid A;Kennedy J;Chioza BA;Ames RM;Cross HE;Puffenberger EG;Harries L;Baple EL;Crosby AH
SNIP1 （Smad核相互作用蛋白1）是广泛表达的TGF-β信号转导通路的转录抑制因子，在人剪接体功能中起关键作用。在这里，我们描述了35例与SNIP1 NM_024700.4:c相关的复杂遗传性神经发育障碍的广泛遗传研究和临床发现。1097A >g, p.（Glu366Gly）变异，在阿米什社区中出现频率很高。这种疾病的主要临床特征包括张力低下、整体发育迟缓、智力残疾、癫痫发作和特征性颅面外观。我们在受影响个体中的基因转录研究定义了许多具有明确神经发育和神经病理作用的分子的基因表达谱改变，可能解释临床结果。总之，这些数据证实了SNIP1基因变异是常染色体隐性复杂神经发育障碍的一个原因，并为SNIP1的分子作用提供了重要的见解，这可能解释了受影响个体的主要临床结果，为未来的研究确定了潜在的治疗途径。神经发育障碍是一组可能在家庭中遗传的疾病，其特征是大脑的生长、发育和功能受损。这可能导致神经精神问题、运动功能受损、学习、语言和/或非语言交流受损。这些情况可能与癫痫有关，其特征是大脑中反复出现异常电活动。在这里，我们确认创始人SNIP1基因变异是阿米什人常染色体隐性复杂神经发育障碍的原因。我们提供临床特征的详细描述，以及临床管理建议。我们的遗传研究确定了与SNIP1基因改变相关的受影响儿童基因表达模式的改变。这项研究发现了在大脑发育和功能中起重要作用的几种蛋白质的异常，可能解释了这种疾病的临床特征。
SNIP1 (Smad nuclear interacting protein 1) is a widely expressed transcriptional suppressor of the TGF-β signal-transduction pathway which plays a key role in human spliceosome function. Here, we describe extensive genetic studies and clinical findings of a complex inherited neurodevelopmental disorder in 35 individuals associated with a SNIP1 NM_024700.4:c.1097A>G, p.(Glu366Gly) variant, present at high frequency in the Amish community. The cardinal clinical features of the condition include hypotonia, global developmental delay, intellectual disability, seizures, and a characteristic craniofacial appearance. Our gene transcript studies in affected individuals define altered gene expression profiles of a number of molecules with well-defined neurodevelopmental and neuropathological roles, potentially explaining clinical outcomes. Together these data confirm this SNIP1 gene variant as a cause of an autosomal recessive complex neurodevelopmental disorder and provide important insight into the molecular roles of SNIP1, which likely explain the cardinal clinical outcomes in affected individuals, defining potential therapeutic avenues for future research. Neurodevelopmental disorders are a group of conditions that may be inherited in families, characterized by impairments of the growth, development and function of the brain. This may result in neuropsychiatric problems, impaired motor function, impaired learning, language and/or non-verbal communication. These conditions may be associated with epilepsy, characterised by recurrent abnormal electrical activity in the brain. Here we confirm a founder SNIP1 gene variant as a cause of an autosomal recessive complex neurodevelopmental disorder in the Amish. We provide a detailed description of the clinical features of the condition alongside clinical management recommendations. Our genetic studies identify altered gene expression patterns in affected children associated with the SNIP1 genetic alteration. This identified abnormalities in several proteins with important roles in brain development and function, potentially explaining the clinical features of the condition.
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影响因子：
14.9
作者：
Mistry J;Chuguransky S;Williams L;Qureshi M;Salazar GA;Sonnhammer ELL;Tosatto SCE;Paladin L;Raj S;Richardson LJ;Finn RD;Bateman A
通讯作者：
Bateman A
影响因子：
5.3
作者：
Monies D;Abouelhoda M;AlSayed M;Alhassnan Z;Alotaibi M;Kayyali H;Al-Owain M;Shah A;Rahbeeni Z;Al-Muhaizea MA;Alzaidan HI;Cupler E;Bohlega S;Faqeih E;Faden M;Alyounes B;Jaroudi D;Goljan E;Elbardisy H;Akilan A;Albar R;Aldhalaan H;Gulab S;Chedrawi A;Al Saud BK;Kurdi W;Makhseed N;Alqasim T;El Khashab HY;Al-Mousa H;Alhashem A;Kanaan I;Algoufi T;Alsaleem K;Basha TA;Al-Murshedi F;Khan S;Al-Kindy A;Alnemer M;Al-Hajjar S;Alyamani S;Aldhekri H;Al-Mehaidib A;Arnaout R;Dabbagh O;Shagrani M;Broering D;Tulbah M;Alqassmi A;Almugbel M;AlQuaiz M;Alsaman A;Al-Thihli K;Sulaiman RA;Al-Dekhail W;Alsaegh A;Bashiri FA;Qari A;Alhomadi S;Alkuraya H;Alsebayel M;Hamad MH;Szonyi L;Abaalkhail F;Al-Mayouf SM;Almojalli H;Alqadi KS;Elsiesy H;Shuaib TM;Seidahmed MZ;Abosoudah I;Akleh H;AlGhonaium A;Alkharfy TM;Al Mutairi F;Eyaid W;Alshanbary A;Sheikh FR;Alsohaibani FI;Alsonbul A;Al Tala S;Balkhy S;Bassiouni R;Alenizi AS;Hussein MH;Hassan S;Khalil M;Tabarki B;Alshahwan S;Oshi A;Sabr Y;Alsaadoun S;Salih MA;Mohamed S;Sultana H;Tamim A;El-Haj M;Alshahrani S;Bubshait DK;Alfadhel M;Faquih T;El-Kalioby M;Subhani S;Shah Z;Moghrabi N;Meyer BF;Alkuraya FS
通讯作者：
Alkuraya FS
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
影响因子：
4.3
作者：
Li, Qiang;An, Jian;Yu, Long
通讯作者：
Yu, Long