MARS variant associated with both recessive interstitial lung and liver disease and dominant Charcot-Marie-Tooth disease.
MARS variant associated with both recessive interstitial lung and liver disease and dominant Charcot-Marie-Tooth disease.
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DOI：
10.1016/j.ejmg.2018.04.005
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发表时间：
2018-10
影响因子：
1.9
通讯作者：
Harel T
中科院分区：
文献类型：
--
作者：
Rips J;Meyer-Schuman R;Breuer O;Tsabari R;Shaag A;Revel-Vilk S;Reif S;Elpeleg O;Antonellis A;Harel T
氨酰-tRNA合成酶（ARSs）是广泛表达的酶，负责在蛋白质翻译期间将tRNA与同源氨基酸装载。非经典功能越来越多地被认识到，包括转录和翻译控制以及细胞外信号传导。编码几种ARS的基因中的单等位基因突变已在轴突Charcot-Marie-Tooth（CMT 2）疾病中被鉴定，而ARS基因座中的双等位基因突变与多组织综合征相关，包括中枢神经系统、肺和肝。我们报告一个非血缘关系的男婴，表现为输血依赖性贫血、甲状腺功能减退、胆汁淤积、间质性肺病和发育迟缓。全外显子组测序（WES）显示MARS基因编码甲硫氨酰-tRNA合成酶的两个变体（p.Tyr307Cys和p.Arg618Cys）具有复合杂合性。双等位基因MARS突变与间质性肺病和肝病（ILLD）相关。有趣的是，p.Arg618Cys变异，从一个未受影响的父亲继承，以前在一个常染色体显性迟发型CMT 2家族中报道。酵母互补试验证实了p.Arg618Cys的致病性，但建议保留p.Tyr307Cys的功能。我们的研究结果强调了与ARS突变相关的表型变异性，并表明单等位基因MARS相关CMT 2发病中的遗传或环境修饰因素。
Aminoacyl-tRNA synthetases (ARSs) are ubiquitously expressed enzymes responsible for charging tRNA with cognate amino acids during protein translation. Non-canonical functions are increasingly recognized, and include transcription and translation control and extracellular signaling. Monoallelic mutations in genes encoding several ARSs have been identified in axonal Charcot-Marie-Tooth (CMT2) disease, whereas biallelic mutations in ARS loci have been associated with multi-tissue syndromes, variably involving the central nervous system, lung, and liver. We report a male infant of non-consanguineous origin, presenting with successive onset of transfusion-dependent anemia, hypothyroidism, cholestasis, interstitial lung disease, and developmental delay. Whole-exome sequencing (WES) revealed compound heterozygosity for two variants (p.Tyr307Cys and p.Arg618Cys) in MARS, encoding methionyl-tRNA synthetase. Biallelic MARS mutations are associated with interstitial lung and liver disease (ILLD). Interestingly, the p.Arg618Cys variant, inherited from an unaffected father, was previously reported in a family with autosomal dominant late-onset CMT2. Yeast complementation assays confirmed pathogenicity of p.Arg618Cys, yet suggested retained function of p.Tyr307Cys. Our findings underscore the phenotypic variability associated with ARS mutations, and suggest genetic or environmental modifying factors in the onset of monoallelic MARS-associated CMT2.
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DOI：
10.1161/atvbaha.115.307087
发表时间：
2016-04
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Castranova D;Davis AE;Lo BD;Miller MF;Paukstelis PJ;Swift MR;Pham VN;Torres-Vázquez J;Bell K;Shaw KM;Kamei M;Weinstein BM
通讯作者：
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影响因子：
9.8
作者：
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通讯作者：
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DOI：
10.1111/j.1749-6632.1999.tb08617.x
发表时间：
1999-01-01
期刊：
CHARCOT-MARIE-TOOTH DISORDERS
影响因子：
--
作者：
Seeman, P;Mazanec, R;Rautenstrauss, B
通讯作者：
Rautenstrauss, B
DOI：
10.1136/jnnp-2013-305049
发表时间：
2013-11
期刊：
Journal of neurology, neurosurgery, and psychiatry
影响因子：
--
作者：
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通讯作者：
Inherited Neuropathy Consortium
影响因子：
9.8
作者：
Antonellis, A;Ellsworth, RE;Green, ED
通讯作者：
Green, ED