Impaired riboflavin transport due to missense mutations in SLC52A2 causes Brown-Vialetto-Van Laere syndrome.
Impaired riboflavin transport due to missense mutations in SLC52A2 causes Brown-Vialetto-Van Laere syndrome.
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DOI：
10.1007/s10545-012-9513-y
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发表时间：
2012-11
影响因子：
4.2
通讯作者：
Prokisch, Holger
中科院分区：
文献类型：
--
作者：
Haack, Tobias B.;Makowski, Christine;Yao, Yoshiaki;Graf, Elisabeth;Hempel, Maja;Wieland, Thomas;Tauer, Ulrike;Ahting, Uwe;Mayr, Johannes A.;Freisinger, Peter;Yoshimatsu, Hiroki;Inui, Ken;Strom, Tim M.;Meitinger, Thomas;Yonezawa, Atsushi;Prokisch, Holger
布朗 - 维亚莱托 - 范拉尔综合征（BVVLS [MIM 211530]）是一种罕见的神经系统疾病，其特征为婴儿期起病的感音神经性耳聋和脑桥 - 延髓麻痹。编码核黄素转运蛋白2（hRFT2）的SLC52A3（以前称为C20orf54）基因的突变已在数例BVVLS患者中被确定为相关的分子遗传学因素。仅对一个病例进行外显子组测序显示，编码核黄素转运蛋白3（hRFT3，核黄素转运蛋白家族的另一个成员）的SLC52A2基因的两个致病突变的复合杂合性也与BVVLS相关。过表达研究证实，两个突变等位基因的基因产物都具有降低的核黄素转运活性。虽然SLC52A3的突变导致血浆核黄素水平降低，这与SLC52A3在从食物中摄取核黄素的作用相符，但SLC52A2突变的个体血浆核黄素浓度正常，这一发现与推测的SLC52A2在核黄素从血液摄取进入靶细胞的功能相符。我们的研究结果有助于理解人类核黄素代谢，并强调了其在BVVLS发病机制中的作用，从而为高剂量核黄素治疗提供了合理依据。
Brown-Vialetto-Van Laere syndrome (BVVLS [MIM 211530]) is a rare neurological disorder characterized by infancy onset sensorineural deafness and ponto-bulbar palsy. Mutations in SLC52A3 (formerly C20orf54), coding for riboflavin transporter 2 (hRFT2), have been identified as the molecular genetic correlate in several individuals with BVVLS. Exome sequencing of just one single case revealed that compound heterozygosity for two pathogenic mutations in the SLC52A2 gene coding for riboflavin transporter 3 (hRFT3), another member of the riboflavin transporter family, is also associated with BVVLS. Overexpression studies confirmed that the gene products of both mutant alleles have reduced riboflavin transport activities. While mutations in SLC52A3 cause decreased plasma riboflavin levels, concordant with a role of SLC52A3 in riboflavin uptake from food, the SLC52A2-mutant individual had normal plasma riboflavin concentrations, a finding in line with a postulated function of SLC52A2 in riboflavin uptake from blood into target cells. Our results contribute to the understanding of human riboflavin metabolism and underscore its role in the pathogenesis of BVVLS, thereby providing a rational basis for a high-dose riboflavin treatment.
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影响因子：
4.2
作者：
Bosch, Annet M.;Abeling, Nico G. G. M.;Waterham, Hans R.
通讯作者：
Waterham, Hans R.
影响因子：
3.9
作者：
Ho, Gladys;Yonezawa, Atsushi;Christodoulou, John
通讯作者：
Christodoulou, John
影响因子：
3.7
作者：
Sathasivam, Sivakumar
通讯作者：
Sathasivam, Sivakumar
影响因子：
5.5
作者：
Yonezawa, Atsushi;Masuda, Satohiro;Inui, Ken-ichi
通讯作者：
Inui, Ken-ichi
影响因子：
7.1
作者：
GOODMAN, SI
通讯作者：
GOODMAN, SI