Spectrum of HNF1A and GCK mutations in Canadian families with maturity-onset diabetes of the young (MODY).
OBJECTIVE
Maturity-onset diabetes of the young (MODY) is a subtype of type 2 diabetes characterized by autosomal-dominant inheritance and early onset. The pathophysiology of MODY is primarily defective insulin secretion resulting from mutations in at least 6 different genes. Most affected patients harbour mutations in either GCK (encoding glucokinase, also called MODY2) and HNF1A (encoding hepatic nuclear factor-1alpha, also called MODY3). We studied Canadian probands to determine if they had mutations in MODY2 or MODY3 genes.


METHODS
We used genomic DNA sequencing of probands from 9 previously unreported Canadian MODY families.


RESULTS
Five MODY probands had mutations in HNF1A, of which 4 were novel (namely IVS5-1delTAG, E275fsdelGAAG, F268S and L44fsdelC) and 4 had mutations in GCK, of which 2 were novel (E237K and L324P). These mutations expand the spectrum of MODY mutations and bring the total number of Canadian MODY families that have been molecularly defined in our laboratory to 15 (8 MODY3 and 7 MODY2).


CONCLUSIONS
Because of the growing evidence that molecular diagnosis may affect prognosis and treatment, this information may be important in future for Canadian MODY families and their physicians.
Robarts Research Institute, London, Ont.
James L
JL
McKinney
Henian
H
Cao
John F
JF
Robinson
Daniel L
DL
Metzger
Elizabeth
E
Cummings
D Christie
DC
Riddell
Susan R
SR
Sanderson
Daniele
D
Pacaud
Josephine
J
Ho
Robert A
RA
Hegele
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002170:Canada / Q000453:epidemiology; D002648:Child; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics*; D005192:Family Health; D005260:Female; D000081410:Germinal Center Kinases; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
D004268:DNA-Binding Proteins; D000081410:Germinal Center Kinases; C496487:HNF1A protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; D009687:Nuclear Proteins; D014157:Transcription Factors; D051537:Hepatocyte Nuclear Factor 1; D017346:Protein Serine-Threonine Kinases