The phenotypic spectrum of X-linked, infantile onset ALG13-related developmental and epileptic encephalopathy.
The phenotypic spectrum of X-linked, infantile onset ALG13-related developmental and epileptic encephalopathy.
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作者：
Datta AN;Bahi-Buisson N;Bienvenu T;Buerki SE;Gardiner F;Cross JH;Heron B;Kaminska A;Korff CM;Lepine A;Lesca G;McTague A;Mefford HC;Mignot C;Milh M;Piton A;Pressler RM;Ruf S;Sadleir LG;de Saint Martin A;Van Gassen K;Verbeek NE;Ville D;Villeneuve N;Zacher P;Scheffer IE;Lemke JR
天冬酰胺连接糖基化13（ALG 13）缺陷在文献中反复描述为发育性和癫痫性脑病（DEE）的临床表型。大多数病例是携带复发性ALG 13从头变异的女性，p。（Asn 107 Ser），转铁蛋白电泳正常。我们描述了38个个体的表型谱，37个女孩和1个男孩，其中16个是新的，22个是已发表的，最常见的致病性ALG 13变异p。（Asn 107 Ser），并另外报告了携带其他可能致病性ALG 13变体的三个个体的表型。表型谱通常包括药物耐药性癫痫伴癫痫痉挛，大多数在出生后前6个月内发作，一半病例伴痉挛持续性。强直性发作是最常见的额外发作类型。脑电图显示高度心律失常，并且在所有病例的三分之一中，在疾病的后期出现快速活动发作伴电减量。ALG 13相关的DEE通常与严重至严重的发育迟缓相关;三分之一的病例获得了截肢，而有目的的手部使用很少或完全不存在。手刻板和运动障碍，包括肌张力障碍或舞蹈手足徐动症相对频繁。语言沟通能力缺乏或很差，眼神交流和追求往往受到损害。X连锁ALG 13相关的DEE通常表现为West综合征，伴有严重至严重的发育迟缓。它主要是由复发性从头错义变体p引起的。（Asn107Ser）。全面的功能研究将能够证明或反驳与先天性糖基化障碍的关联。
Asparagine‐linked glycosylation 13 (ALG13) deficiencies have been repeatedly described in the literature with the clinical phenotype of a developmental and epileptic encephalopathy (DEE). Most cases were females carrying the recurrent ALG13 de novo variant, p.(Asn107Ser), with normal transferrin electrophoresis. We delineate the phenotypic spectrum of 38 individuals, 37 girls and one boy, 16 of them novel and 22 published, with the most common pathogenic ALG13 variant p.(Asn107Ser) and additionally report the phenotype of three individuals carrying other likely pathogenic ALG13 variants. The phenotypic spectrum often comprised pharmacoresistant epilepsy with epileptic spasms, mostly with onset within the first 6 months of life and with spasm persistence in one‐half of the cases. Tonic seizures were the most prevalent additional seizure type. Electroencephalography showed hypsarrhythmia and at a later stage of the disease in one‐third of all cases paroxysms of fast activity with electrodecrement. ALG13‐related DEE was usually associated with severe to profound developmental delay; ambulation was acquired by one‐third of the cases, whereas purposeful hand use was sparse or completely absent. Hand stereotypies and dyskinetic movements including dystonia or choreoathetosis were relatively frequent. Verbal communication skills were absent or poor, and eye contact and pursuit were often impaired. X‐linked ALG13‐related DEE usually manifests as West syndrome with severe to profound developmental delay. It is predominantly caused by the recurrent de novo missense variant p.(Asn107Ser). Comprehensive functional studies will be able to prove or disprove an association with congenital disorder of glycosylation.
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错义突变热点识别神经发育障碍基因和功能域
影响因子：
25
作者：
Geisheker MR;Heymann G;Wang T;Coe BP;Turner TN;Stessman HAF;Hoekzema K;Kvarnung M;Shaw M;Friend K;Liebelt J;Barnett C;Thompson EM;Haan E;Guo H;Anderlid BM;Nordgren A;Lindstrand A;Vandeweyer G;Alberti A;Avola E;Vinci M;Giusto S;Pramparo T;Pierce K;Nalabolu S;Michaelson JJ;Sedlacek Z;Santen GWE;Peeters H;Hakonarson H;Courchesne E;Romano C;Kooy RF;Bernier RA;Nordenskjöld M;Gecz J;Xia K;Zweifel LS;Eichler EE
通讯作者：
Eichler EE
DOI：
10.1007/8904_2017_53
发表时间：
2018-01-01
期刊：
JIMD REPORTS, VOL 40
影响因子：
--
作者：
Galama, Wienke H.;Verhaagen-van den Akker, Sandra L. J.;Verrips, Aad
通讯作者：
Verrips, Aad
影响因子：
5
作者：
Bolfoni, M. R.;Pappen, F. G.;Jacinto, R. C.
通讯作者：
Jacinto, R. C.
影响因子：
5.6
作者：
Berg, Anne T.;Berkovic, Samuel F.;Scheffer, Ingrid E.
通讯作者：
Scheffer, Ingrid E.
影响因子：
64.8
作者：
通讯作者：
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