Mutations in VPS33B, encoding a regulator of SNARE-dependent membrane fusion, cause arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome
Mutations in VPS33B, encoding a regulator of SNARE-dependent membrane fusion, cause arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome
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DOI：
10.1038/ng1325
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发表时间：
2004-04-01
期刊：
影响因子：
30.8
通讯作者：
Maher, ER
中科院分区：
文献类型：
--
作者：
Gissen, P;Johnson, CA;Maher, ER
ARC综合征（在线人类孟德尔遗传数据库编号208085）是一种常染色体隐性多系统疾病，其特征为先天性神经源性多发性关节挛缩、肾小管功能障碍以及伴有胆管发育不全和低γ-谷氨酰转肽酶（gGT）活性的新生儿胆汁淤积。血小板功能障碍较为常见。患病婴儿发育不良，通常在出生后第一年内死亡（1 - 5）。为了阐明ARC的分子基础，我们将该疾病定位在15q26.1上一个7厘摩的区间，然后在14个患有ARC的家系中鉴定出VPS33B基因的种系突变。VPS33B编码C类酵母液泡蛋白分选基因Vps33的一个同源物，该同源物包含一个Sec1样结构域，在调节囊泡与靶标SNARE复合物形成以及随后的膜融合过程中起重要作用（6 - 9）
ARC syndrome ( OMIM 208085) is an autosomal recessive multisystem disorder characterized by neurogenic arthrogryposis multiplex congenita, renal tubular dysfunction and neonatal cholestasis with bile duct hypoplasia and low gamma glutamyl transpeptidase (gGT) activity. Platelet dysfunction is common. Affected infants do not thrive and usually die in the first year of life(1-5). To elucidate the molecular basis of ARC, we mapped the disease to a 7-cM interval on 15q26.1 and then identified germline mutations in the gene VPS33B in 14 kindreds with ARC. VPS33B encodes a homolog of the class C yeast vacuolar protein sorting gene, Vps33, that contains a Sec1-like domain important in the regulation of vesicle-to-target SNARE complex formation and subsequent membrane fusion(6-9).