A novel homozygous p.R1105X mutation of the AP4E1 gene in twins with hereditary spastic paraplegia and mycobacterial disease.
A novel homozygous p.R1105X mutation of the AP4E1 gene in twins with hereditary spastic paraplegia and mycobacterial disease.
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DOI：
10.1371/journal.pone.0058286
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Boisson-Dupuis S
中科院分区：
文献类型：
--
作者：
Kong XF;Bousfiha A;Rouissi A;Itan Y;Abhyankar A;Bryant V;Okada S;Ailal F;Bustamante J;Casanova JL;Hirst J;Boisson-Dupuis S
我们报告了近亲家庭出生的同卵双胞胎患有智力障碍、进行性痉挛性截瘫和身材矮小。有趣的是，这两个孩子都出现了由卡介苗 (BCG) 活疫苗引起的淋巴结炎。两种综合征——遗传性痉挛性截瘫（HSP）和分枝杆菌病——因此同时发生。全外显子组测序 (WES) 揭示了 AP4E1 基因的纯合无义突变 (p.R1105X)，并经桑格测序证实。 p.R1105X 突变对 AP4E1 mRNA 水平没有影响，但导致 AP-4ε 蛋白和 AP-4 复合物其他成分的水平降低，如蛋白质印迹、免疫沉淀和免疫荧光所示。因此，AP-4ε亚基的C端部分在维持AP-4复合物的完整性方面发挥着重要作用。未发现 IL-12/IFN-γ 轴或氧化爆发途径异常。总之，我们鉴定出患有与 HSP 和分枝杆菌疾病相关的常染色体隐性 AP-4 缺陷的双胞胎，这表明 AP-4 可能在神经和免疫系统中发挥重要作用。
We report identical twins with intellectual disability, progressive spastic paraplegia and short stature, born to a consanguineous family. Intriguingly, both children presented with lymphadenitis caused by the live Bacillus Calmette-Guérin (BCG) vaccine. Two syndromes – hereditary spastic paraplegia (HSP) and mycobacterial disease – thus occurred simultaneously. Whole-exome sequencing (WES) revealed a homozygous nonsense mutation (p.R1105X) of the AP4E1 gene, which was confirmed by Sanger sequencing. The p.R1105X mutation has no effect on AP4E1 mRNA levels, but results in lower levels of AP-4ε protein and of the other components of the AP-4 complex, as shown by western blotting, immunoprecipitation and immunofluorescence. Thus, the C-terminal part of the AP-4ε subunit plays an important role in maintaining the integrity of the AP-4 complex. No abnormalities of the IL-12/IFN-γ axis or oxidative burst pathways were identified. In conclusion, we identified twins with autosomal recessive AP-4 deficiency associated with HSP and mycobacterial disease, suggesting that AP-4 may play important role in the neurological and immunological systems.
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影响因子：
13.9
作者：
Blackstone C
通讯作者：
Blackstone C
DOI：
10.1084/jem.20101597
发表时间：
2010-10-25
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Byun M;Abhyankar A;Lelarge V;Plancoulaine S;Palanduz A;Telhan L;Boisson B;Picard C;Dewell S;Zhao C;Jouanguy E;Feske S;Abel L;Casanova JL
通讯作者：
Casanova JL
DOI：
10.1038/nrn2946
发表时间：
2011-01
期刊：
Nature reviews. Neuroscience
影响因子：
--
作者：
Blackstone C;O'Kane CJ;Reid E
通讯作者：
Reid E
影响因子：
11.8
作者：
Burgos, Patricia V.;Mardones, Gonzalo A.;Rojas, Adriana L.;daSilva, Luis L. P.;Prabhu, Yogikala;Hurley, James H.;Bonifacino, Juan S.
通讯作者：
Bonifacino, Juan S.
DOI：
10.1111/j.1749-6632.2010.05834.x
发表时间：
2010-01-01
期刊：
YEAR IN HUMAN AND MEDICAL GENETICS: NEW TRENDS IN MENDELIAN GENETICS
影响因子：
--
作者：
Alcais, Alexandre;Quintana-Murci, Lluis;Casanova, Jean-Laurent
通讯作者：
Casanova, Jean-Laurent