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KMID : 1038820190220060581
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Pediatric Gastroenterology, Hepatology & Nutrition
2019 Volume.22 No. 6 p.581 ~ p.587
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A Novel VPS33B Variant Identified by Exome Sequencing in a Patient with Arthrogryposis-Renal Dysfunction-Cholestasis Syndrome
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Lee Min-Ju
Suh Chae-Ri
Shin Jeong-Hee
Lee Jee-Hyun
Lee Yoon
Eun Baik-Lin
Yoo Kee-Hwan
Shim Jung-Ok
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Abstract
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Arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome is a rare autosomal recessive multisystemic disease that is associated with the liver, kidney, skin, and central nervous and musculoskeletal systems. ARC occurs as a result of mutations in the VPS33B (Vacuolar protein sorting 33 homolog B) or VIPAR (VPS33B interacting protein, apical-basolateral polarity regulator) genes. A female infant presented with neonatal cholestasis with a severe clinical outcome. She was diagnosed with ARC syndrome using targeted exome sequencing (TES). Exome sequencing revealed compound heterozygous mutations, c.707A>T and c.239+5G>A, in VPS33B, where c.707A>T was a novel variant; the resultant functional protein defects were predicted via in silico analysis. c.239+5G>A, a pathogenic mutation that affects splicing, is found in less than 0.1% of the general population. Invasive techniques, such as liver biopsies, did not contribute to a differential diagnosis of ARC syndrome; thus, early TES together with clinical presentations constituted an apparently accurate diagnostic procedure.
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KEYWORD
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Neonatal cholestasis, VIPAR, VPS33B, Mutation
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