DETECTION OF HNF1A GENE MUTATION RELATED TO MATURITY-ONSET DIABETES OF THE YOUNG (MODY) IN A DIABETES MELLITUS PATIENT USING SEQUENCING

Abstrak

Maturity-Onset Diabetes of the Young (MODY) is a monogenic form of diabetes caused by genetic mutations, including those in the HNF1A gene, and is often misdiagnosed as type 1 or type 2 diabetes. This study aims to detect HNF1A gene mutations in patients suspected of having MODY using Sanger sequencing to support a more specific diagnosis. The research methods include DNA isolation from two patient samples, followed by amplification of ten exons of the HNF1A gene using conventional PCR, analysis of amplification results using agarose gel electrophoresis, and and sequence analysis of Sanger sequencing results. Sequencing results were analyzed using BioEdit and ClustalW software to identify mutations relative to the HNF1A gene reference sequence (NM_001306179.2). Six point mutations were identified in the HNF1A gene, distributed across exons 7, 9, and 10, consisting of one silent mutation (p.Leu459Leu), four missense mutations (p. Gln460His, p.Ser486Asn, p.Ser581Gly, and p.Val705Leu). The identified mutations have the potential to affect the structure and function of the HNF1A protein, including the transcription activation domain, which is crucial in regulating the expression of target genes. This study demonstrates that the detection of genetic mutations, especially in HNF1A, is important in accurately diagnosing MODY as well as determining appropriate theraphy approaches, such as the use of sulfonylureas as an alternative to insulin.