In this issue of Diabetes, Colclough et al. (1) report interesting data suggesting that the current genetic testing strategy for monogenic diabetes should be modified, extending it by default to genes known to cause syndromic forms of the disease.Section 1.01 Monogenic diabetes presents with a broad and heterogeneous clinical spectrum due to mutations in a single gene (2,3) and affects 1-5% of patients with diabetes (2,4). To date, several distinct subtypes of monogenic diabetes have been identified (2), including neonatal diabetes (diagnosed within the first 6 months of life), syndromic diabetes (very rare forms of hyperglycemia occurring in combination with extrapancreatic abnormalities, which include but are not limited to urogenital morphological abnormalities, hearing, and vision loss), and maturity-onset diabetes of the young (MODY), which is, by far, the most frequent. MODY follows an autosomal dominant inheritance pattern (5) and has been related to mutations in 14 different genes (OMIM [Online Mendelian Inheritance in Man] project no. 606391). Accordingly, outside of very early infancy, the current genetic testing procedure for monogenic diabetes only targets the 14 MODY genes, while the genes responsible for syndromic diabetes, hitherto considered distinct from MODY, are tested solely in the presence of suggestive clinical features (6).
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