VPS33B mutation with ichthyosis, cholestasis, and renal dysfunction but without arthrogryposis: incomplete ARC syndrome phenotype.
Arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome is a rare multisystem disorder first described in 1979 and recently ascribed to mutation in VPS33B, whose product acts in intracellular trafficking. Arthrogryposis, spillage of various substances in the urine, and conjugated hyperbilirubinemia define an ARC core phenotype, in some patients associated with ichthyosis, central nervous system malformation, deafness, and platelet abnormalities. We describe a patient with cholestasis, aminoaciduria, ichthyosis, partial callosal agenesis, and sensorineural deafness who, although homozygous for the novel VPS33B mutation 971delA/K324fs, predicted to abolish VPS33B function, did not exhibit arthrogryposis. The phenotypes associated with VPS33B mutation may include incomplete ARC.
Bull
Laura N
LN
University of California San Francisco Liver Center Laboratory and Department of Medicine, San Francisco General Hospital, San Francisco, CA, USA.
Mahmoodi
Venus
V
Baker
Alastair J
AJ
Jones
Rosamond
R
Strautnieks
Sandra S
SS
Thompson
Richard J
RJ
Knisely
A S
AS
D061085:Agenesis of Corpus Callosum; D001176:Arthrogryposis / Q000235:genetics; D002779:Cholestasis / Q000175:diagnosis* / Q000235:genetics; D017809:Fatal Outcome; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000175:diagnosis / Q000235:genetics; D006801:Humans; D006932:Hyperbilirubinemia / Q000209:etiology; D007057:Ichthyosis / Q000175:diagnosis* / Q000235:genetics; D007223:Infant; D007674:Kidney Diseases / Q000175:diagnosis* / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D009154:Mutation; D010641:Phenotype; D000608:Renal Aminoacidurias / Q000175:diagnosis / Q000235:genetics; D013577:Syndrome; D033921:Vesicular Transport Proteins
D008565:Membrane Proteins; C411584:VPS33B protein, human; D033921:Vesicular Transport Proteins