1136-P: Utility of Mining a Genetic Diagnostic Laboratory for Atypical Diabetes Cases

Abstract

The emerging heterogeneity of “T1D” and “T2D” has revealed a spectrum of atypical diabetes (AD), comprising genetically and phenotypically heterogeneous forms of DM that do not fit the usual pattern of T1D or T2D. We aimed to develop a strategy to find AD cases for the Rare and Atypical Diabetes Network (RADIANT) Study and elucidate the genetic contribution to AD phenotypes, based on potential for genetic locus discovery and phenotypic expansion of established DM or non-DM loci. In collaboration with the Baylor Genetics Laboratory, we reviewed two datasets of patients with a range of abnormal phenotypes referred for nuclear exome sequencing (nES) and mitochondrial DNA sequencing (mtDNA). Factors considered for candidacy were: age at testing (early-onset or later-onset with features atypical of T2D), strong family history, syndromic features, existing variant interpretations and gene-phenotype associations, and expert review by clinical diabetologists. Suspicion for AD was raised in 31/287 nES referrals and 87/115 mtDNA referrals that listed diabetes as a part of the phenotype (Figure 1). Some interesting cases of unexplained DM included: siblings with consanguineous parents suggesting recessive disease and early-onset syndromic DM. As genetic testing is often ordered for suspected rare disease or atypical presentation of common disease, genetic diagnostic laboratory data are a rich source for discovery of AD patients.View largeDownload slideView largeDownload slide DisclosureM. E. Fang: None. J. A. Rosenfeld: Employee; Self; Baylor Genetics. M. J. Redondo: Advisory Panel; Self; Provention Bio, Inc. M. Tosur: Advisory Panel; Self; Provention Bio, Inc. P. Liu: Other Relationship; Self; Baylor Genetics. A. Balasubramanyam: None. J. Posey: None. Radiant study group: n/a.