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Combined genetic analyses can achieve efficient diagnostic yields for subjects with Alagille syndrome and incomplete Alagille syndrome
Author(s) -
Ohashi Kei,
Togawa Takao,
Sugiura Tokio,
Ito Koichi,
Endo Takeshi,
Aoyama Kohei,
Negishi Yutaka,
Kudo Toyoichiro,
Ito Reiko,
Saitoh Shinji
Publication year - 2017
Publication title -
acta paediatrica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.772
H-Index - 115
eISSN - 1651-2227
pISSN - 0803-5253
DOI - 10.1111/apa.13981
Subject(s) - alagille syndrome , jag1 , multiplex ligation dependent probe amplification , biliary atresia , medicine , microarray , genetics , pathology , gastroenterology , cholestasis , biology , exon , notch signaling pathway , gene , gene expression , transplantation , liver transplantation
Aim 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. Methods 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. Results 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%). Conclusion Combined genetic analyses achieved efficient diagnostic yields for subjects with Alagille syndrome and incomplete Alagille syndrome.