AUTHOR=Iskandar Kristy , Simanjaya Susan , Indrawan Taufik , Kalim Alvin Santoso , Marcellus  , Heriyanto Didik Setyo , Gunadi  

TITLE=Is There Any Mosaicism in REarranged During Transfection Variant in Hirschsprung Disease’s Patients?

JOURNAL=Frontiers in Pediatrics

VOLUME=10

YEAR=2022

URL=https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2022.842820

DOI=10.3389/fped.2022.842820

ISSN=2296-2360

ABSTRACT=<sec><title>Background</title><p>Hirschsprung disease (HSCR) is a heterogeneous genetic disease characterized by the absence of ganglion cells in the intestinal tract. The <italic>REarranged during Transfection (RET)</italic> is the most responsible gene for its pathogenesis. RET’s somatic mosaicisms have been reported for HSCR; however, they are still under-recognized. Therefore, we determined the frequency of somatic mutation of <italic>RET</italic> rs2435357 in HSCR patients at our institution.</p></sec><sec><title>Methods</title><p>We performed <italic>RET</italic> rs2435357 genotyping from 73 HSCR formalin-fixed and paraffin-embedded (FFPE) rectal and 60 non-HSCR controls using the PCR-RFLP method. Subsequently, we compared those frequencies of genotypes for <italic>RET</italic> rs2435357 with our previous genotyping data from 93 HSCR blood specimens.</p></sec><sec><title>Results</title><p>The frequencies of genotypes for <italic>RET</italic> rs2435357 in HSCR paraffin-embedded rectal were CC 0, CT 11 (15%), and TT 62 (85%), whereas their frequencies in HSCR blood samples were CC 4 (4.3%), CT 22 (23.7%), and TT 67 (72%). Those frequencies differences almost reached a significant level (<italic>p</italic> = 0.06). Moreover, the frequency of <italic>RET</italic> rs2435357 risk allele (T) was significantly higher in HSCR patients (135/146, 92.5%) than controls (46/120, 38.3%) (<italic>p</italic> = 3.4 × 10<sup>–22</sup>), with an odds ratio of 19.74 (95% confidence interval = 9.65–40.41).</p></sec><sec><title>Conclusion</title><p>Our study suggests somatic mosaicism in HSCR patients. These findings further imply the complexity of the pathogenesis of HSCR. Moreover, our study confirms the <italic>RET</italic> rs2435357 as a significant genetic risk factor for HSCR patients.</p></sec>