Knowledge Transfer in thePost-Genome World:

keeping up is not good enoughTimothy D. Smith

Rebholz-Schuhmann et al. 2005

Jensen et al. 2006

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

SPECIES human

GENE NAME TGM2

ACCESSION NM_198951

VARIANT c.989T>G

BASE CHANGE TYPE Substitution

PROTEIN EFFECT -

PHENOTYPE Impaired enzyme activity; glucose metabolism disorder

CDC28

Cyclin-dependant kinase 1

Cdk1

hairy

white

T98G

L23A

The mutation in exon 7 c.989T>G (p.M330R), was

found in a Danish patient (D79) with early onset type

2 diabetes. Porzio et al. 2007

c.989T>G

TGM2:c.989T>G

...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).

Solutions

Knowledge Transfer in thePost-Genome World:

keeping up is not good enoughTimothy D. Smith