Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Current Pediatric Reviews
  4. Volume 21, Issue 2
  5. Article
Volume 21, Issue 2
  • ISSN: 1573-3963
  • E-ISSN: 1875-6336

Abstract

Background

Cholestatic liver disease is an important cause of morbidity and mortality and a leading indication for liver transplantation in children. These include diseases, such as biliary atresia, Alagille syndrome, progressive familial intrahepatic cholestasis, sclerosing cholangitis, bile acid synthesis defects, and many others.

Case Presentation

NGS was used as a diagnostic tool to identify the genetic cause in the patient with cholestatic syndrome and to figure out and describe what mutation will be found. In the present observation, the cholestasis syndrome with low GGT activity and intense pruritus was the leading symptom of the patient. The examination also revealed other characteristic features of osteo-oto-hepato-enteric syndrome. The patient had facial features that mimicked Alagille syndrome, which complicated the diagnostic search. Moreover, the genetic test revealed two new pathogenic variants in the gene.

Conclusion

This clinical observation demonstrates the importance of a multidisciplinary approach in the diagnosis of rare genetic diseases and using WES, which can accelerate the diagnosis compared with outdated gene panels.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cpr/10.2174/0115733963264010231213103328
2024-02-16
2024-12-25

  • From This Site

    /content/journals/cpr/10.2174/0115733963264010231213103328
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. KarpenS.J. Pediatric cholestasis: Epidemiology, genetics, diagnosis, and current management.Clin. Liver Dis.202015311511910.1002/cld.89532685137
     [Google Scholar]
  2. SuchyF.J. SokolR.J. BalistreriW.F. Liver diseases in children.UKCambridge University Press202110.1017/9781108918978
     [Google Scholar]
  3. KriegermeierA. GreenR. Pediatric cholestatic liver disease: Review of bile acid metabolism and discussion of current and emerging therapies.Front. Med.2020714910.3389/fmed.2020.0014932432119
     [Google Scholar]
  4. AlmesM. SpraulA. RuizM. GirardM. RoquelaureB. LabordeN. GottrandF. TurquetA. LamireauT. DabadieA. BonnetonM. ThebautA. RohmerB. LacailleF. BrouéP. FabreA. Mention-MulliezK. BouligandJ. JacqueminE. GonzalesE. Targeted-capture next-generation sequencing in diagnosis approach of pediatric cholestasis.Diagnostics2022125116910.3390/diagnostics1205116935626323
     [Google Scholar]
  5. GoldbergA. MackC.L. Inherited cholestatic diseases in the era of personalized medicine.Clin. Liver Dis.202015310510910.1002/cld.87232257121
     [Google Scholar]
  6. LeeI.H. LinY. AlvarezW.J. Hernandez-FerrerC. MandlK.D. KongS.W. WEScover: Selection between clinical whole exome sequencing and gene panel testing.BMC Bioinformatics202122125926810.1186/s12859‑021‑04178‑534016036
     [Google Scholar]
  7. SoucheE. BeltranS. BrosensE. BelmontJ.W. FossumM. RiessO. GilissenC. ArdeshirdavaniA. HougeG. van GijnM. Clayton-SmithJ. SynofzikM. de LeeuwN. DeansZ.C. DincerY. EckS.H. van der CrabbenS. BalasubramanianM. GraessnerH. SturmM. FirthH. FerliniA. NabboutR. De BaereE. LiehrT. MacekM. MatthijsG. SchefferH. BauerP. YntemaH.G. WeissM.M. Recommendations for whole genome sequencing in diagnostics for rare diseases.Eur. J. Hum. Genet.20223091017102110.1038/s41431‑022‑01113‑x35577938
     [Google Scholar]
  8. ChenH-L. LiH-Y. WuJ-F. WuS-H. ChenH-L. YangY-H. HsuY-H. LiouB-Y. ChangM-H. NiY-H. Panel-based next-generation sequencing for the diagnosis of cholestatic genetic liver diseases: Clinical utility and challenges.J. Pediatr.2019205153159.e610.1016/j.jpeds.2018.09.028
     [Google Scholar]
  9. EsteveC. FrancescattoL. TanP.L. BourchanyA. De LeusseC. MarinierE. BlanchardA. BourgeoisP. Brochier-ArmanetC. BruelA.L. DelarueA. DuffourdY. Ecochard-DugelayE. HeryG. HuetF. GauchezP. GonzalesE. Guettier-BouttierC. KomutaM. LacosteC. MaudinasR. MazodierK. RimetY. RivièreJ.B. RoquelaureB. SigaudyS. StephenneX. Thauvin-RobinetC. ThevenonJ. SarlesJ. LevyN. BadensC. GouletO. HugotJ.P. KatsanisN. FaivreL. FabreA. Loss-of-function mutations in UNC45A cause a syndrome associating cholestasis, diarrhea, impaired hearing, and bone fragility.Am. J. Hum. Genet.2018102336437410.1016/j.ajhg.2018.01.00929429573
     [Google Scholar]
  10. GötzeT. BlessingH. GrillhöslC. GernerP. HoerningA. Neonatal cholestasis – differential diagnoses, current diagnostic procedures, and treatment.Front Pediatr.20153434826137452
     [Google Scholar]
  11. KawaharaS. ImagawaK. TakeuchiS. IwasakiT. OkadaY. NakamuraY. SaitoS. SasakiT. MasumotoK. TakadaH. Differential diagnosis of neonatal cholestasis by genetic testing: A case report.J. Pediatr. Surg. Case Rep.20239410265810.1016/j.epsc.2023.102658
     [Google Scholar]
  12. Duclaux-LorasR. LebretonC. BertheletJ. Charbit-HenrionF. NicolleO. Revenu de CourtilsC. WaichS. ValovkaT. KhiatA. RabantM. RacineC. GuerreraI.C. BaptistaJ. MaheM.M. HessM.W. DurelB. LefortN. BanalC. ParisotM. TalbotecC. LacailleF. Ecochard-DugelayE. DemirA.M. VogelG.F. FaivreL. RodriguesA. FowlerD. JaneckeA.R. MüllerT. HuberL.A. Rodrigues-LimaF. RuemmeleF.M. UhligH.H. Del BeneF. MichauxG. Cerf-BensussanN. ParlatoM. UNC45A deficiency causes microvillus inclusion disease–like phenotype by impairing myosin VB–dependent apical trafficking.J. Clin. Invest.202213210e15499710.1172/JCI15499735575086
     [Google Scholar]
  13. LeeC.F. MelkaniG.C. BernsteinS.I. The UNC-45 myosin chaperone: From worms to flies to vertebrates.Int. Rev. Cell Mol. Biol.201431310314410.1016/B978‑0‑12‑800177‑6.00004‑925376491
     [Google Scholar]
  14. GazdaL The myosin chaperone UNC-45 is organized in tandem modules to support myofilament formation in C. elegans. Cell20131521– 2183195
     [Google Scholar]
  15. WohlgemuthS.L. CrawfordB.D. PilgrimD.B. The myosin co-chaperone UNC-45 is required for skeletal and cardiac muscle function in zebrafish.Dev. Biol.2007303248349210.1016/j.ydbio.2006.11.02717189627
     [Google Scholar]
  16. ChenD. LiS. SinghR. SpinetteS. SedlmeierR. EpsteinH.F. Dual function of the UNC-45b Chaperone with myosin and GATA4 in cardiac development.J. Cell Sci.2012125Pt 16jcs.10643510.1242/jcs.10643522553207
     [Google Scholar]
/content/journals/cpr/10.2174/0115733963264010231213103328
Loading
Newly Described Mutations of the UNC45A Gene in Infants with Jaundice and Pruritus
Curr Pediatr Rev 21, 192 (2025); https://doi.org/10.2174/0115733963264010231213103328
/content/journals/cpr/10.2174/0115733963264010231213103328
/content/journals/cpr/10.2174/0115733963264010231213103328
Loading

Data & Media loading...


  • Article Type:     Case Report
Keyword(s): congenital diarrhea; diagnosis; jaundice; osteootohepatoenteric syndrome; UNC45A gene; Сholestasis

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test