We analysed the TGM2 gene in 205 patients with clinically defined Maturity Onset Diabetes of the Young (MODY) or early-onset type 2 diabetes. We found two novel heterozygous mutations (c.989T>G, p.M330R; c.992T>A, p.I331N), which were not detected in 300 normoglycemic controls. All mutations were in residues which are located close to the catalytic site and impaired transamidating activity in vitro. Gene expression of TGM family genes and localization of TG2 in normal human pancreas indicated that TG2 is the only transglutaminase significantly expressed in human pancreatic islet cells. We conclude that reduced TG2 activity can contribute to disorders of glucose metabolism possibly via an impairment of insulin secretion. Porzio et al. 2007
SPECIEShuman GENE NAMETGM2 ACCESSIONNM_198951 VARIANTc.989T>G BASE CHANGE TYPESubstitution PROTEIN EFFECT- PHENOTYPEImpaired enzyme activity; glucose metabolism disorder
...the substitution of a nucelotide at position 989 to guanine...
A second heterozygous mutation in exon 7 c.992T>A (p.I331N) was identified in a French family (F193, Fig. 1B). The mutation was detected in the index case (Fig. 1B, II-2), who presented with diabetes at the age of 39 (therapy: diet) and in two diabetic siblings (II-4, II-6, treated with diet and OHA, respectively).