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

P Gissen, C A Johnson, N V Morgan, J M Stapelbroek, T Forshew, W N Cooper, P J McKiernan, L W J Klomp, A A M Morris, J E Wraith, P McClean, S A Lynch, R J Thompson, B Lo, O W Quarrell, M Di Rocco, R C Trembath, H Mandel, S Wali, F E KaretA S Knisely, R H J Houwen, D A Kelly, E R Maher

Research output: Contribution to journalArticlepeer-review

287 Citations (Scopus)

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(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).
Original languageEnglish
Pages (from-to)400 - 404
Number of pages5
JournalNature Genetics
Volume36
Issue number4
DOIs
Publication statusPublished - Apr 2004

Fingerprint

Dive into the research topics of 'Mutations in VPS33B, encoding a regulator of SNARE-dependent membrane fusion, cause arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome'. Together they form a unique fingerprint.

Cite this