Novel NBAS mutations and fever-related recurrent acute liver failure in Chinese children: a retrospective study
| Autor: | Mei-Hong Zhang, Yi Lu, Jian-She Wang, A S Knisely, Jing-Yu Gong, Yi-Ling Qiu, Li-Min Dou, Jia-Qi Li, Weisha Luan |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Candidate gene medicine.medical_specialty Pathology China Fever Nonsense mutation medicine.disease_cause Gastroenterology Frameshift mutation 03 medical and health sciences 0302 clinical medicine Asian People Recurrence Internal medicine Recurrent acute liver failure Medicine Missense mutation Humans NBAS lcsh:RC799-869 Child Exome sequencing Retrospective Studies Mutation medicine.diagnostic_test business.industry Whole exome sequencing Infant General Medicine Jaundice Liver Failure Acute Neoplasm Proteins 030104 developmental biology Liver biopsy Child Preschool lcsh:Diseases of the digestive system. Gastroenterology medicine.symptom business 030217 neurology & neurosurgery Acute liver failure Research Article |
| Zdroj: | BMC Gastroenterology BMC Gastroenterology, Vol 17, Iss 1, Pp 1-7 (2017) |
| ISSN: | 1471-230X |
| Popis: | Background Underlying causes in Chinese children with recurrent acute liver failure (RALF), including liver crises less than full acute liver failure, are incompletely understood. We sought to address this by searching for genes mutated in such children. Methods Five unrelated Chinese boys presenting between 2012 and 2015 with RALF of unexplained etiology were studied. Results of whole exome sequencing were screened for mutations in candidate genes. Mutations were verified in patients and their family members by Sanger sequencing. All 5 boys underwent liver biopsy. Results NBAS was the only candidate gene mutated in more than one patient (biallelic mutations, 3 of 5 patients; 5 separate mutations). All NBAS mutations were novel and predictedly pathogenic (frameshift insertion mutation c.6611_6612insCA, missense mutations c.2407G > A and c.3596G > A, nonsense mutation c.586C > T, and splicing-site mutation c.5389 + 1G > T). Of these mutations, 3 lay in distal (C-terminal) regions of NBAS, a novel distribution. Unlike the 2 patients without NBAS mutations, the 3 patients with confirmed NBAS mutations all suffered from a febrile illness before each episode of liver crisis (fever-related RALF), with markedly elevated alanine aminotransferase and aspartate aminotransferase activities 24-72 h after elevation of body temperature, succeeded by severe coagulopathy and mild to moderate jaundice. Conclusions As in other countries, so too in China; NBAS disease is a major cause of fever-related RALF in children. The mutation spectrum of NBAS in Chinese children seems different from that described in other populations. Electronic supplementary material The online version of this article (doi:10.1186/s12876-017-0636-3) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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