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Whole Exome Sequencing Identifies a Novel Pathogenic RET Variant in Hirschsprung Disease

By Wei Wu, Li Lu, Weijue Xu, Jiangbin Liu, Jun Sun, Lulu Zheng, Qingfeng Sheng and Zhibao Lv


Hirschsprung disease is a birth defect characterized by complete absence of neuronal ganglion cells from a portion of the intestinal tract. To uncover genetic variants contributing to HSCR, we performed whole exome sequencing on seven members of an HSCR family. With the minor allele frequency (MAF) calculated by gnomAD, we finally filtered a total of 1,059 rare variants in this family (MAF < 0.1%). With the mode of inheritance and pathogenicity scores by bioinformatics tools, we identified an in-frameshift variant p.Phe147del in RET as the disease-causing variant. Further analysis revealed that the in-frameshift variant may function by disrupting the glycosylation of RET protein. To our knowledge, this is the first study to report the in-frameshift variant p.Phe147del in RET responsible for heritable HSCR

Topics: whole exome sequencing, Hirschsprung disease, RET variant, minor allele frequencies, bioinformatics, Genetics, QH426-470
Publisher: Frontiers Media S.A.
Year: 2019
DOI identifier: 10.3389/fgene.2018.00752/full
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