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J Pediatr Genet 2021; 10(04): 323-325
DOI: 10.1055/s-0040-1714361
Case Report

Novel UGT1A1 Gene Mutations in a Boy with Crigler–Najjar Syndrome Type II

David Pérez-Solís 
1   Department of Pediatrics, San Agustín University Hospital, Avilés, Spain
,
Bárbara Montes-Zapico
1   Department of Pediatrics, San Agustín University Hospital, Avilés, Spain
,
Ana-Cristina Rodríguez-Dehli
1   Department of Pediatrics, San Agustín University Hospital, Avilés, Spain
,
María García-Hoyos
2   Department of Medical Genetics, The National Institute of Genomic Medicine, S.L. Paterna, Spain
,
Mireia Arroyo-Hernández
1   Department of Pediatrics, San Agustín University Hospital, Avilés, Spain
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Abstract

In this article, we reported a patient with Crigler–Najjar syndrome type II with high-unconjugated bilirubin levels that decreased after phenobarbital treatment. The patient had two novel missense mutations in the UGT1A1 gene and a promoter variant in one allele. One mutation was c.1001T > C, that predicted leucine to proline substitution at position 334 (p.Leu334Pro). The other, c.1139A > G, predicted glutamic acid to glycine replacement at position 380 (p.Glu380Gly). In silico analysis indicated that both mutations are likely pathogenic.

Keywords

Crigler–Najjar syndrome - hyperbilirubinemia - hereditary - genetic variation

Note

Written informed parental consent was obtained for both print and online publication of this case.




Publication History

Received: 09 May 2020

Accepted: 07 June 2020

Article published online:
29 July 2020

© 2020. Thieme. All rights reserved.

Georg Thieme Verlag KG
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  • References

  • 1 Arias IM, Gartner LM, Cohen M, Ezzer JB, Levi AJ. Chronic nonhemolytic unconjugated hyperbilirubinemia with glucuronyl transferase deficiency. Clinical, biochemical, pharmacologic and genetic evidence for heterogeneity. Am J Med 1969; 47 (03) 395-409
    CrossrefPubMedSearch in Google Scholar
  • 2 Erlinger S, Arias IM, Dhumeaux D. Inherited disorders of bilirubin transport and conjugation: new insights into molecular mechanisms and consequences. Gastroenterology 2014; 146 (07) 1625-1638
    CrossrefPubMedSearch in Google Scholar
  • 3 Abuduxikuer K, Fang L-J, Li L-T, Gong J-Y, Wang J-S. UGT1A1 genotypes and unconjugated hyperbilirubinemia phenotypes in post-neonatal Chinese children: a retrospective analysis and quantitative correlation. Medicine (Baltimore) 2018; 97 (49) e13576
    CrossrefPubMedSearch in Google Scholar
  • 4 Kadakol A, Sappal BS, Ghosh SS. et al. Interaction of coding region mutations and the Gilbert-type promoter abnormality of the UGT1A1 gene causes moderate degrees of unconjugated hyperbilirubinaemia and may lead to neonatal kernicterus. J Med Genet 2001; 38 (04) 244-249
    CrossrefPubMedSearch in Google Scholar
  • 5 Servedio V, d'Apolito M, Maiorano N. et al. Spectrum of UGT1A1 mutations in Crigler-Najjar (CN) syndrome patients: identification of twelve novel alleles and genotype-phenotype correlation. Hum Mutat 2005; 25 (03) 325
    CrossrefPubMedSearch in Google Scholar
  • 6 Romagnoli C, Tiberi E, Barone G. et al. Validation of transcutaneous bilirubin nomogram in identifying neonates not at risk of hyperbilirubinaemia: a prospective, observational, multicenter study. Early Hum Dev 2012; 88 (01) 51-55
    CrossrefPubMedSearch in Google Scholar
  • 7 Harbrecht BG, Rosengart MR, Bukauskas K, Zenati MS, Marsh Jr JW, Geller DA. Assessment of transcutaneous bilirubinometry in hospitalized adults. J Am Coll Surg 2008; 206 (06) 1129-1136
    CrossrefPubMedSearch in Google Scholar