编码SNARE依赖性膜融合调节因子的VPS33B发生突变，会导致关节弯曲-肾功能不全-胆汁淤积（ARC）综合征。

Mutations in VPS33B, encoding a regulator of SNARE-dependent membrane fusion, cause arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome.

作者信息

Gissen Paul, Johnson Colin A, Morgan Neil V, Stapelbroek Janneke M, Forshew Tim, Cooper Wendy N, McKiernan Patrick J, Klomp Leo W J, Morris Andrew A M, Wraith James E, McClean Patricia, Lynch Sally A, Thompson Richard J, Lo Bryan, Quarrell Oliver W, Di Rocco Maja, Trembath Richard C, Mandel Hanna, Wali S, Karet Fiona E, Knisely A S, Houwen Roderick H J, Kelly Deirdre A, Maher Eamonn R

机构信息

Section of Medical and Molecular Genetics, University of Birmingham, and Liver Unit, Birmingham Children's Hospital, UK.

出版信息

Nat Genet. 2004 Apr;36(4):400-4. doi: 10.1038/ng1325. Epub 2004 Mar 28.

DOI:10.1038/ng1325

PMID:15052268

Abstract

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. 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.

摘要

ARC综合征（OMIM 208085）是一种常染色体隐性多系统疾病，其特征为先天性多发性神经源性关节挛缩、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。血小板功能障碍很常见。受影响的婴儿生长发育不良，通常在出生后第一年内死亡。为了阐明ARC的分子基础，我们将该疾病定位到15q26.1上一个7厘摩的区间，然后在14个患有ARC的家族中鉴定出基因VPS33B中的种系突变。VPS33B编码C类酵母液泡蛋白分选基因Vps33的一个同源物，该基因包含一个Sec1样结构域，对调节囊泡与靶标SNARE复合体的形成以及随后的膜融合很重要。