Molecular diagnosis of pediatric patients with citrin deficiency in China: SLC25A13 mutation spectrum and the geographic distribution.
Molecular diagnosis of pediatric patients with citrin deficiency in China: SLC25A13 mutation spectrum and the geographic distribution.
复制标题
中国柑橘缺乏症儿科患者的分子诊断：SLC25A13 突变谱和地理分布
DOI：
10.1038/srep29732
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发表时间：
2016-07-11
影响因子：
4.6
通讯作者：
Song YZ
中科院分区：
文献类型：
--
作者：
Lin WX;Zeng HS;Zhang ZH;Mao M;Zheng QQ;Zhao ST;Cheng Y;Chen FP;Wen WR;Song YZ
柠檬酸缺乏症（Citrin deficiency，CD）是一种由SLC 25 A13基因双等位基因突变引起的孟德尔遗传病。Citrin缺乏引起的新生儿肝内胆汁淤积症（NICCD）是儿童CD的主要表型，其确诊依赖于SLC 25 A13基因分析。我国幅员辽阔，人口众多，但我国CD患者的SLC 25 A13基因型特征还远未明确。通过复杂的分子分析，该研究在中国大陆诊断了154例新发CD患者，并鉴定了9个新的有害SLC 25 A13突变，即c.103A G，[c.329 − 154_c.468 + 2352 del 2646; c.468 + 2392_c.468 + 2393ins23]、c.493CT、c.755 − 1G C、c.845_c.848 + 1delG、c.933_c.933 + 1insGCAG、c.1381G T、c.1452 + 1G A和c.1706_1707delTA。在本组确诊的274例CD患者中，共检测到41例SLC 25 A13突变/变异。c.775CT、c.851_854del4、c.1078CT、IVS 11 + 1G A、c.1364G T、c.1399CT和IVS 16 ins 3 kb 7个突变的地理分布差异显著。在所鉴定的53种基因型中，只有c.851_854del4/c.851_854del4和c.851_854del4/c.1399C T两种基因型在地理分布上存在差异。北方群体的SLC 25 A13等位基因异质性高于南方群体。这些发现丰富了SLC 25 A13突变谱，为NICCD的确诊和不同地区相关分子靶点的确定提供了可靠依据。
Citrin deficiency (CD) is a Mendelian disease due to biallelic mutations of SLC25A13 gene. Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is the major pediatric CD phenotype, and its definite diagnosis relies on SLC25A13 genetic analysis. China is a vast country with a huge population, but the SLC25A13 genotypic features of CD patients in our country remains far from being well clarified. Via sophisticated molecular analysis, this study diagnosed 154 new CD patients in mainland China and identified 9 novel deleterious SLC25A13 mutations, i.e. c.103A G, [c.329 − 154_c.468 + 2352del2646; c.468 + 2392_c.468 + 2393ins23], c.493C T, c.755 − 1G C, c.845_c.848 + 1delG, c.933_c.933 + 1insGCAG, c.1381G T, c.1452 + 1G A and c.1706_1707delTA. Among the 274 CD patients diagnosed by our group thus far, 41 SLC25A13 mutations/variations were detected. The 7 mutations c.775C T, c.851_854del4, c.1078C T, IVS11 + 1G A, c.1364G T, c.1399C T and IVS16ins3kb demonstrated significantly different geographic distribution. Among the total 53 identified genotypes, only c.851_854del4/c.851_854del4 and c.851_854del4/c.1399C T presented different geographic distribution. The northern population had a higher level of SLC25A13 allelic heterogeneity than those in the south. These findings enriched the SLC25A13 mutation spectrum and brought new insights into the geographic distribution of the variations and genotypes, providing reliable evidences for NICCD definite diagnosis and for the determination of relevant molecular targets in different Chinese areas.