Cholestasis Due to USP53 Deficiency.
Journal
Journal of pediatric gastroenterology and nutrition
ISSN: 1536-4801
Titre abrégé: J Pediatr Gastroenterol Nutr
Pays: United States
ID NLM: 8211545
Informations de publication
Date de publication:
01 05 2021
01 05 2021
Historique:
pubmed:
20
10
2020
medline:
10
7
2021
entrez:
19
10
2020
Statut:
ppublish
Résumé
Although a number of genetic forms of cholestasis have been identified, the genetic etiology of disease remains unidentified in a subset of cholestasis patients. Whole exome sequencing (WES) was performed in DNA from patients diagnosed with cholestasis, at different points on the continuum from progressive familial intrahepatic cholestasis to benign recurrent intrahepatic cholestasis, in whom no disease mutations in known cholestasis genes had been identified. Candidate genes were then assessed in a larger patient sample, by targeted next-generation sequencing (NGS). Disease features at presentation and follow-up were collected from available medical records. By WES, we identified 3 patients with homozygous mutations in USP53. Screening of USP53 in a larger set of patients identified 4 additional patients with homozygous mutations in USP53. Six of the 7 patients had deletion mutations, and 1 had a missense mutation; 3 of the patients were siblings, all bearing a deletion that also disrupted neighboring MYOZ2. Age of onset ranged from early infancy to adolescence. Cholestasis tended to be biochemically mild and intermittent, and responsive to medication. Liver fibrosis was, however, present in all 4 patients who were biopsied, and splenomegaly was apparent in 5 of 7 at last ultrasound. Two groups recently identified patients with liver disease and mutation in USP53. We have now identified biallelic mutation in USP53 in 7 further patients with cholestasis, from 5 families. Most individuals had evidence of chronic liver disease, and long-term follow-up is recommended.
Identifiants
pubmed: 33075013
pii: 00005176-202105000-00007
doi: 10.1097/MPG.0000000000002926
pmc: PMC8549450
doi:
Substances chimiques
Carrier Proteins
0
MYOZ2 protein, human
0
Muscle Proteins
0
USP53 protein, human
EC 3.4.19.12
Ubiquitin-Specific Proteases
EC 3.4.19.12
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
667-673Subventions
Organisme : NIDDK NIH HHS
ID : U01 DK062453
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002535
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK094828
Pays : United States
Organisme : NHGRI NIH HHS
ID : UM1 HG006493
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK062456
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK062500
Pays : United States
Organisme : NHGRI NIH HHS
ID : U24 HG008956
Pays : United States
Organisme : NIDDK NIH HHS
ID : U24 DK062456
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.
Déclaration de conflit d'intérêts
R.J.T. consults for Albireo, Mirum, GenerationBio, Alnylam, Qing Bile, Horizon, Sana, and Retrophin and has share options in Qing Bile and GenerationBio. Other authors report no conflicts of interest. M.S. is now an employee of Illumina Inc.
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