Clinical Domain Working Groups

The Monogenic Diabetes Expert Panel will develop a sustainable process for systematic consensus review for pathogenicity and submission to ClinVar of MODY, neonatal diabetes genes, Wolfram syndrome, mitochondrial diabetes and other syndromic genes agreed upon by consensus.

We will develop gene-specific rules, curate at an expert panel level, and deposit curations into ClinVar variants in genes implicated in monogenic autoimmune diabetes: AIRE (Type 1 autoimmune polyendocrinopathy syndrome and autoimmune diabetes), FOXP3 (immunodysregulation, polyendocrinopathy, and enteropathy, X-linked syndrome; IPEX), LRBA (immunodysregulation and autoimmune diabetes), IL2RA (immunodeficiency 41 with lymphoproliferation and autoimmunity), STAT3 (neonatal diabetes and polyautoimmune disease), and SLC29A3 (histocytosis with non-autoimmune diabetes). We will also focus on genes implicated in monogenic insulin resistance and/or lipodystrophy: INSR (syndromes of extreme insulin resistance); PIK3R1 (SHORT syndrome); AGPAT2, BSCL2, and CAVIN1 (congenital generalized lipodystrophy); LMNA, PPARG, and PLIN1 (familial partial lipodystrophy), and POLD1 and MFN2 (genes implicated in colorectal cancer susceptibility and Charcot-Marie-Tooth disease respectively but with certain variants implicated in partial lipodystrophy).