액솜 염기서열 분석을 이용한 한국인 조기 발현 당뇨병 유전자에 관한 연구
Identification of novel candidate variants for MODY by whole exome sequencing in Korean MODY families
Abstract
Background: Maturity-onset diabetes of the young (MODY) is one of monogenic diabetes mellitus (DM) that is caused by a single gene defect. To date, thirteen MODY genes have been identified worldwide. However, there is big discrepancy in genetic locus between the Asian MODY patients and Caucasian\'s one. We conducted the whole exome sequencing in Korean MODY families to identify novel MODY genes and compare the result with Caucasian\'s one. Methods: The six MODY probands and their possible family members (parents and siblings) were included for whole exome sequencing. We conduct a case-control comparison in the family members and selected the variants which were commonly found in both MODY proband and DM family member and were not found in non-DM family member in one family. The selected variants were scanned for the candidate genes for MODY. Results: All exonic regions were 19,935~20,314 in 6 MODY probands. After filtering, functional variants were 224~250. After case-control method, variants with possibility of causing the disease were 31~63. After scanning for DM associated genes, two novel variants were identified in family 5 and 6 - c.C559G:p.Gln187Glu in SYT9 and c.C620T:p.Thr207Ile in PTPRD. We placed emphasis on the functional variants, but one synonymous exonic mutation, c.G294A/p.Gln98Gln in exone 2 chromosome 7 position 127254976 of PAX4 (MODY9), was identified in both proband and her mother in family 1. In Family 2 to 4, we could not find the disease causing variant for MODY. Conclusions: We could not find any disease causative alleles among known MODY 1-13 genes except one synonymous SNV in PAX4. We confirmed again that there is huge discrepancy between Asian and Caucasian races in the case of generic variants of MODY. To establish the function of two novel variants of SYT9 and PTPRD, more study is necessary.