This poster (#0380) will be presented at the ACMG Annual Clinical Genetics Meeting by Daniela del Gaudio, our associate lab director, Thursday March 21: 10:30am-11:30am.  Stop by and learn more

Monogenic diabetes is a group of less common forms of diabetes that account for 1-2% of all diabetes cases.  Monogenic diabetes patients are most often not recognized as being distinct from those with type 1 or type 2 diabetes, even though some forms can frequently be treated very differently.  Thus, if a proper genetic diagnosis is uncovered, it could dramatically improve patient care.  The genetic risk of future offspring or asymptomatic family members could also be established, as well as better prediction of the disease course and possible associated problems.  The most striking example is seen for patients with mutations in the KATP channel genes, who can be effectively treated with oral sulfonylurea drugs rather than insulin, resulting in dramatically improved quality of life and control of diabetes.

We developed a panel for selective enrichment of a set of 56 genes known to play a role in monogenic diabetes followed by next generation sequencing (NGS) using the Illumina MiSeq platform.  To amplify the regions of interest we used the HaloPlex PCR target enrichment system (Agilent Technologies).  The total amount of sequence encompassed by the 56 genes is 144 kb and includes the coding region and 20 bp of flanking intronic sequence. In an initial study, five genomic DNA samples with available exome sequencing data were used to evaluate the validity of this system.  The data obtained from the HaloPlex enrichment system and from the exome sequence of the same samples was analyzed using a custom-developed bioinformatic pipeline and 100% concordance in variant calls was observed between the two platforms within the regions of interest of the genes included in the panel. Validation of this platform for clinical use is in progress and will involve the analysis of 50 anonymized samples with known sequence variations previously identified on a research basis by Sanger sequencing.

The availability of this panel will be ben­eficial as 1) it will allow for more rapid and cost-effective diagnosis of patients with monogenic forms of diabetes by analyzing multiple diabetes genes simultaneously and 2) it will provide a significant diagnostic advantage in a substantial fraction of patients where Sanger-based sequencing often is inefficient, such as in cases with atypical clinical presentation or where clinical information is limited.  The overall goal will be an improvement in the diagnosis and treatment of patients with monogenic diabetes. Aside from its valuable diagnostic utility, this panel will also represent an excellent tool for studying a substantial number of patients where previous analyses have failed to identify a genetic defect and will allow for better genotype-phenotype correlation studies.