title: Mutations in VPS33B, encoding a regulator of SNARE-dependent membrane fusion, cause arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome.
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.
authors.affiliation: Section of Medical and Molecular Genetics, University of Birmingham, and Liver Unit, Birmingham Children's Hospital, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Gissen
authors.forename: Colin A
authors.initials: CA
authors.lastname: Johnson
authors.forename: Neil V
authors.initials: NV
authors.lastname: Morgan
authors.forename: Janneke M
authors.initials: JM
authors.lastname: Stapelbroek
authors.forename: Tim
authors.initials: T
authors.lastname: Forshew
authors.forename: Wendy N
authors.initials: WN
authors.lastname: Cooper
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: McKiernan
authors.forename: Leo W J
authors.initials: LW
authors.lastname: Klomp
authors.forename: Andrew A M
authors.initials: AA
authors.lastname: Morris
authors.forename: James E
authors.initials: JE
authors.lastname: Wraith
authors.forename: Patricia
authors.initials: P
authors.lastname: McClean
authors.forename: Sally A
authors.initials: SA
authors.lastname: Lynch
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Thompson
authors.forename: Bryan
authors.initials: B
authors.lastname: Lo
authors.forename: Oliver W
authors.initials: OW
authors.lastname: Quarrell
authors.forename: Maja
authors.initials: M
authors.lastname: Di Rocco
authors.forename: Richard C
authors.initials: RC
authors.lastname: Trembath
authors.forename: Hanna
authors.initials: H
authors.lastname: Mandel
authors.forename: S
authors.initials: S
authors.lastname: Wali
authors.forename: Fiona E
authors.initials: FE
authors.lastname: Karet
authors.forename: A S
authors.initials: AS
authors.lastname: Knisely
authors.forename: Roderick H J
authors.initials: RH
authors.lastname: Houwen
authors.forename: Deirdre A
authors.initials: DA
authors.lastname: Kelly
authors.forename: Eamonn R
authors.initials: ER
authors.lastname: Maher
mesh_terms: D001176:Arthrogryposis / Q000235:genetics*; D015153:Blotting, Western; D002460:Cell Line; D002779:Cholestasis / Q000235:genetics*; D002884:Chromosomes, Human, Pair 15; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000235:genetics*; D008297:Male; D008561:Membrane Fusion / Q000235:genetics / Q000502:physiology*; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D009154:Mutation; D010957:Plasmids; D011506:Proteins / Q000737:chemistry / Q000235:genetics*; D050600:SNARE Proteins; D013577:Syndrome; D033921:Vesicular Transport Proteins
chemical_list: D008565:Membrane Proteins; D011506:Proteins; D050600:SNARE Proteins; C411584:VPS33B protein, human; D033921:Vesicular Transport Proteins