Antibody-Positive Type 1 Diabetes in a Family With a Pathogenic HNF1A-MODY Variant and Variable Age of Onset

携带致病性HNF1A-MODY变异基因且发病年龄不一的家族性抗体阳性1型糖尿病

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Abstract

Monogenic diabetes (MD) is a relatively rare and heterogeneous group of disorders caused by pathogenic single-gene variants or abnormalities resulting in hyperglycemia. MD represents approximately 3.5% of all diabetes cases diagnosed before age 35 years, though it is possible for MD to develop at later ages. MD diagnoses have implications for precision therapy and cascade genetic testing. A hallmark characteristic suggesting MD is a multigenerational family history of nonobese diabetes diagnosed before age 35 with an autosomal dominant inheritance. However, even with a known family history of genetically confirmed MD, it is possible for an individual within that family to have a different form of diabetes. Here, we present a case from the University of Chicago Monogenic Diabetes Registry of an individual with antibody-positive type 1 diabetes in a family with a history of a genetically confirmed known pathogenic HNF1A variant causing maturity-onset diabetes of the young (MODY) with variable age of onset in affected individuals. This family pedigree showcases that HNF1A-MODY can develop at any age and illustrates the importance of every individual receiving a thorough work-up for accurate diabetes classification, including obtaining antibody testing and genetic testing, when indicated, to provide optimal treatment and management.

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