Mutation in SLC6A9 encoding a glycine transporter causes a novel form of non-ketotic hyperglycinemia in humans.
Mutation in SLC6A9 encoding a glycine transporter causes a novel form of non-ketotic hyperglycinemia in humans.
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DOI：
10.1007/s00439-016-1719-x
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发表时间：
2016-11
期刊：
影响因子：
5.3
通讯作者：
Abu Ali, Qais
中科院分区：
文献类型：
--
作者：
Alfadhel, Majid;Nashabat, Marwan;Al Qahtani, Hanan;Alfares, Ahmed;Al Mutairi, Fuad;Al Shaalan, Hesham;Douglas, Ganka V.;Wierenga, Klaas;Juusola, Jane;Alrifai, Muhammad Talal;Arold, Stefan T.;Alkuraya, Fowzan;Abu Ali, Qais
甘氨酸裂解系统（GCS）催化甘氨酸的降解和由GLDC编码的甘氨酸组分的破坏，AMT和GCSH是甘氨酸脑病（也称为非酮症性高甘氨酸血症（NKH））的唯一已知原因。在本报告中，我们描述了一个近亲家庭，有一个孩子患有NKH，但在与这种情况相关的三个基因中没有任何致病变异。全外显子组测序发现SLC6A9 NM_201649.3: c.1219外显子9有一个新的纯合错义变异与家族内的疾病分离的一种>G （p.s 407gly）。这种变异取代了甘氨酸转运蛋白离子结合位点高度保守的S407，预计会破坏其功能。在小鼠模型中，Slc6a9基因敲除与NKH的等效表型相关，即呼吸窘迫和低张力。这是首次证明甘氨酸转运体的突变可能与人类NKH有关。
Glycine cleavage system (GCS) catalyzes the degradation of glycine and disruption of its components encoded by GLDC, AMT and GCSH are the only known causes of glycine encephalopathy, also known as non-ketotic hyperglycinemia (NKH). In this report, we describe a consanguineous family with one child who presented with NKH, but harbored no pathogenic variants in any of the three genes linked to this condition. Whole-exome sequencing revealed a novel homozygous missense variant in exon 9 of SLC6A9 NM_201649.3: c.1219 A>G (p.Ser407Gly) that segregates with the disease within the family. This variant replaces the highly conserved S407 in the ion-binding site of this glycine transporter and is predicted to disrupt its function. In murine model, knockout of Slc6a9 is associated with equivalent phenotype of NKH, namely respiratory distress and hypotonia. This is the first demonstration that mutation of the glycine transporter can be associated with NKH in humans.
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影响因子：
7.3
作者：
Alexander SP;Kelly E;Marrion N;Peters JA;Benson HE;Faccenda E;Pawson AJ;Sharman JL;Southan C;Davies JA;CGTP Collaborators
通讯作者：
CGTP Collaborators
影响因子：
4.8
作者：
Arribas-Gonzalez, Esther;de Juan-Sanz, Jaime;Lopez-Corcuera, Beatriz
通讯作者：
Lopez-Corcuera, Beatriz
DOI：
10.1097/00075197-200303000-00013
发表时间：
2003-03-01
影响因子：
3.1
作者：
Zhong, Z;Wheeler, MD;Lemasters, JJ
通讯作者：
Lemasters, JJ
影响因子：
9.8
作者：
Tanaka, Akemi J.;Cho, Megan T.;Chung, Wendy K.
通讯作者：
Chung, Wendy K.
DOI：
10.1055/s-0028-1085326
发表时间：
1979-01-01
期刊：
NEUROPADIATRIE
影响因子：
--
作者：
DALLABERNARDINA, B;AICARDI, J;PLOUIN, P
通讯作者：
PLOUIN, P