Novel founder intronic variant in SLC39A14 in two families causing Manganism and potential treatment strategies.
Novel founder intronic variant in SLC39A14 in two families causing Manganism and potential treatment strategies.
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DOI：
10.1016/j.ymgme.2018.04.002
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发表时间：
2018-06
影响因子：
3.8
通讯作者：
Agrawal PB
中科院分区：
文献类型：
--
作者：
Rodan LH;Hauptman M;D'Gama AM;Qualls AE;Cao S;Tuschl K;Al-Jasmi F;Hertecant J;Hayflick SJ;Wessling-Resnick M;Yang ET;Berry GT;Gropman A;Woolf AD;Agrawal PB
先天性锰代谢障碍在儿童中很少见，这些疾病的医疗管理是复杂和具有挑战性的。最近，锰转运蛋白SLC39A14的纯合子外显子突变与一种儿童起病的神经退行性疾病有关，该疾病的特征是脑内锰的蓄积和临床上的锰神经毒性症状，包括帕金森氏症-肌张力障碍。我们对来自阿联酋的两名患有进行性运动障碍和脑矿化的无关女性儿童的DNA样本进行了全外显子测序，在这两名儿童中发现了SLC39A14新的纯合子内含子突变，并证明该突变导致了异常剪接。两名儿童的血清锰水平均持续升高，并被诊断为SLC39A14相关性锰中毒。在四年的时间里，我们对患者1采用了一种多学科的治疗方法，将减少锰的饮食摄入和螯合治疗与对肌张力障碍的症状治疗相结合。我们的治疗策略似乎减缓了疾病的进展，但并没有治愈或逆转已经存在的缺陷。临床医生应该考虑在诊断先天性锰代谢障碍时检测非编码突变，并在这些疾病的治疗中利用多学科方法。
Congenital disorders of manganese metabolism are rare occurrences in children, and medical management of these disorders is complex and challenging. Homozygous exonic mutations in the manganese transporter SLC39A14 have recently been associated with a pediatric-onset neurodegenerative disorder characterized by brain manganese accumulation and clinical signs of manganese neurotoxicity, including parkinsonism-dystonia. We performed whole exome sequencing on DNA samples from two unrelated female children from the United Arab Emirates with progressive movement disorder and brain mineralization, identified a novel homozygous intronic mutation in SLC39A14 in both children, and demonstrated that the mutation leads to aberrant splicing. Both children had consistently elevated serum manganese levels and were diagnosed with SLC39A14-associated manganism. Over a four-year period, we utilized a multidisciplinary management approach for Patient 1 combining decreased manganese dietary intake and chelation with symptomatic management of dystonia. Our treatment strategy appeared to slow disease progression, but did not lead to a cure or reversal of already established deficits. Clinicians should consider testing for noncoding mutations in the diagnosis of congenital disorders of manganese metabolism and utilizing multidisciplinary approaches in the management of these disorders.
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影响因子：
9.8
作者：
Quadri, Marialuisa;Federico, Antonio;Bonifati, Vincenzo
通讯作者：
Bonifati, Vincenzo
影响因子：
9.8
作者：
Park, Julien H.;Hogrebe, Max;Marquardt, Thorsten
通讯作者：
Marquardt, Thorsten
影响因子：
3.4
作者：
Zheng W;Jiang YM;Zhang Y;Jiang W;Wang X;Cowan DM
通讯作者：
Cowan DM
肝肝硬化，肌张力障碍，多性性心血症和高镁血症的综合征是由人类中的锰转运蛋白突变引起的。
影响因子：
9.8
作者：
Tuschl K;Clayton PT;Gospe SM Jr;Gulab S;Ibrahim S;Singhi P;Aulakh R;Ribeiro RT;Barsottini OG;Zaki MS;Del Rosario ML;Dyack S;Price V;Rideout A;Gordon K;Wevers RA;Chong WK;Mills PB
通讯作者：
Mills PB
影响因子：
3.5
作者：
Juneja, Monica;Shamim, Uzma;Faruq, Mohammed
通讯作者：
Faruq, Mohammed