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Newly Described Mutations of the UNC45A Gene in Infants with Jaundice and Pruritus

Anna Degtyareva1, Alina Dokshukina1, Elena Filippova1

  • 1Department of Pediatrics and Clinical Genetics, National Medical, Research Center for Obstetrics, Gynecology, and Perinatology Named after Academician V.I. Kulakov, Moscow, Russia.

Current Pediatric Reviews
|February 20, 2024
PubMed

Insights

Diagnosing rare cholestatic liver diseases in children is challenging. Whole-exome sequencing identified novel UNC45A gene variants, aiding diagnosis in a complex pediatric case.

Area of Science:

  • Genetics
  • Pediatric Gastroenterology
  • Rare Diseases

Background:

  • Cholestatic liver diseases are a significant cause of childhood morbidity and mortality.
  • These conditions necessitate liver transplantation in pediatric patients.
  • Examples include biliary atresia, Alagille syndrome, and progressive familial intrahepatic cholestasis.

Observation:

  • A pediatric patient presented with cholestasis, low gamma-glutamyl transferase (GGT) activity, and intense pruritus.
  • The patient exhibited features suggestive of osteo-oto-hepato-enteric syndrome and facial characteristics mimicking Alagille syndrome.
  • Diagnostic challenges were compounded by the overlapping clinical features.

Findings:

  • Next-generation sequencing (NGS) was employed as a diagnostic tool.
  • Two novel pathogenic variants in the UNC45A gene were identified.
  • These variants are associated with the patient's cholestatic syndrome.

Implications:

  • This case highlights the importance of a multidisciplinary approach for diagnosing rare genetic disorders.
  • Whole-exome sequencing (WES) accelerates diagnosis compared to traditional gene panels.
  • Accurate genetic diagnosis is crucial for effective management of pediatric cholestatic liver diseases.
Abstract

Keywords:
UNC45A genecongenital diarrheadiagnosis.jaundiceosteootohepatoenteric syndromeСholestasis

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