Abstract
While the most common causes for maturity-onset diabetes of the young (MODY) are heterozygous mutations in the genes HNF1A, GCK, HNF4A, HNF1B, NEUROD1, and INS, also other genes have been confirmed to give rise to MODY in isolated cases. One of such genes is the PAX4, encoding transcription factor essential for development of insulin-producing cells.
Its mutation has been reported to cause MODY in two Thai probands, and it was investigated in small MODY groups of European ancestry with negative results. Methods.
By direct sequencing of the PAX4 gene, we tested Czech 53 MODYX probands who fulfill the criteria for MODY, and were negative for mutations in the genes HNF1A, HNF4A, GCK, NEUROD, INS, and structural variants in HNF1A, HNF4A, GCK, and HNF1B. Results.
No disease-causing mutations in the PAX4 gene were detected. The probands carried several polymorphisms (e.g. p.His321Pro in 60% of probands and IVS3+79C>T in 90% probands).
Conclusions. Our carefully selected group of MODYX patients represents - to our best knowledge - the largest cohort of European MODY patients tested for mutations within the PAX4 gene.
Our data indicate that the PAX4 gene has no, or very limited role in etiology of MODY diabetes, among patients of Central European ancestry.