ESPE Abstracts (2014) 82 P-D-1-2-71

Identification of Novel Candidate Gene Variants for Mody by Whole Exome Sequencing in Korean Mody Families

Un Mi Cho, Yae Ji Shim, Byung Ho Choi & Cheol Woo Ko

Kyungpook National University Hospital, Daegu, Republic of Korea

Background: Maturity-onset diabetes of the young (MODY) is one of monogenic diabetes caused by a single gene defect. To date, 13 MODY genes have been identified. However, there is big discrepancy in genetic locus between the Asian MODY patients and Caucasian’s one.

Objective and hypotheses: We conducted the whole exome sequencing in Korean clinical MODY families to identify novel variants for MODY and compare the result with Caucasian’s one.

Method: The six clinical MODY probands and their family members were included for exome sequencing. To identify the disease causing mutations, the variants in dbSNP135 and TIARA database for Korean and the variants with minor allele frequencies >0.5% of the 1000 g were excluded. We selected only the functional variants (gain of stop codon, frameshifts, and nonsynonymous SNV resulting in disruption of canonical splice cites) and conduct a case–control comparison in the family members. The selected variants were scanned for the interested gene list for MODY.

Results: All exonic regions were 18 981–20 178 in six probands. After filtering, the functional variants were 224–250. After case–control method, variants with possibility of causing the disease were 31–63 in each one side pedigree. After scanning for the interested gene list for MODY, three novel variants, c.620C>T; p.Thr207Ile in PTPRD, c.559C>G; p.Gln187Glu in SYT9, and c.1526T>G; p.Val509Gly in WFS1 were identified in three families respectively.

Conclusion: We could not find any disease causative alleles among known MODY 1–13 genes. We confirmed again that there is huge discrepancy between Asian and Caucasian races in the case of generic variants of MODY. Further evaluation is necessary about the role of PTPRD, SYT9, and WFS1 in glucose metabolism and normal insulin release from pancreatic beta cell in the future.

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