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- Title
Combined genetic analyses can achieve efficient diagnostic yields for subjects with Alagille syndrome and incomplete Alagille syndrome.
- Authors
Ohashi, Kei; Togawa, Takao; Sugiura, Tokio; Ito, Koichi; Endo, Takeshi; Aoyama, Kohei; Negishi, Yutaka; Kudo, Toyoichiro; Ito, Reiko; Saitoh, Shinji
- Abstract
<bold>Aim: </bold>We evaluated combined genetic analyses with targeted next-generation sequencing (NGS), multiplex ligation probe amplification (MLPA) of Jagged1 (JAG1) genes and microarray comparative genomic hybridisation (CGH) in subjects with Alagille syndrome, incomplete clinical features of Alagille syndrome and biliary atresia.<bold>Methods: </bold>Subjects recruited from April 2013 to December 2015 underwent a targeted NGS analysis, including JAG1 and Notch homolog 2 (NOTCH2). If no mutations were detected in JAG1 or NOTCH2, or if copy number variations were suggested by the NGS analysis, we performed an MLPA analysis of JAG1. We also performed a microarray CGH analysis with whole-exon deletion detected by the MLPA analysis.<bold>Results: </bold>We analysed 30 subjects with Alagille syndrome, nine with incomplete Alagille syndrome and 17 with biliary atresia and detected pathogenic mutations in JAG1 or NOTCH2 in 24/30 subjects with Alagille syndrome and in 4/9 subjects with incomplete Alagille syndrome. No pathogenic mutations were detected in subjects with biliary atresia. The frequency of JAG1 mutations was as follows: single nucleotide variants (51.9%), small insertion or deletion (29.6%) and gross deletion (18.5%).<bold>Conclusion: </bold>Combined genetic analyses achieved efficient diagnostic yields for subjects with Alagille syndrome and incomplete Alagille syndrome.
- Subjects
ALAGILLE syndrome; NUCLEOTIDE sequencing; BILIARY atresia; NOTCH genes; GENETIC mutation; DNA microarrays; DIAGNOSIS
- Publication
Acta Paediatrica, 2017, Vol 106, Issue 11, p1817
- ISSN
0803-5253
- Publication type
journal article
- DOI
10.1111/apa.13981