Background: Among the currently known variants of maturity-onset diabetes of the young (MODY) subtypes 13 are the most prevalent, while their relative frequencies vary in different populations. Other types of MODY are more rare, although the studies addressing their prevalences are limited. Recent implementation of next-generation sequencing (NGS) enables simultaneos analysis of multiple candidate genes making it an attracive approach in various monogenic disorders, including MODY.
Objective and hypotheses: To evaluate the frequency of different subtypes of MODY in the Russian population using a targeted NGS.
Method: *224 subjects (age range, 0.325 years; females, n=106 males, n=118) were included in the study. The patients fulfilled the following MODY criteria: diabetes or intermediate hyperglycemia, absence of β-cell autoimmunity (ICA, GAD, IA2, and IAA antibodies), preserved C-peptide secretion. Diabetes panel genes were sequenced using a custom Ion Ampliseq gene panel and PGM semiconductor sequencer (Ion Torrent). Non-synonymous sequence variants were rated as probably pathogenic if they had allele frequency <1% and pathogenic ljb database scores (ANNOVAR).
Results: *129 pathogenic or probably pathogenic mutations were found in 65.6% of the patients (n=147). Mutations in GCK were found in 107 cases (47.8%); HNF1A, in 16 cases (7.1%); HNF4A, in four cases; (1.8%); HNF1B, in six cases (2.7%); KLF11, in two cases (0.9%); CEL, in four cases (1.8%); PAX4, in two cases (0.9%); INS, in one cases (0.4%); BLK, in three cases (1.3%); and ABCC8, in four cases (1.8%). Five patients had digenic mutations.
Conclusion: MODY2 was shown to be the most prevalent in the studied population. The panel sequencing was useful in identifying rare subtypes of MODY as well as mutations in other genes with potentilally modifying effect on the phenotype.
Funding: This work was supported by the Alfa-Endo Program of Charities Aid Foundation (CAF) Russia.
01 - 03 Oct 2015
European Society for Paediatric Endocrinology