Molecular background and clinical characteristics of HNF1A MODY in a Polish population.
OBJECTIVE
Knowing the molecular background of monogenic diabetes in affected individuals influences the clinical practice. Mutations in the HNF1A gene are the most frequent cause of MODY. The aim of the present study was to identify the genetic and clinical characteristics of HNF1A MODY in a Polish population, and the prevalence of diabetic complications and renal malformations.


METHODS
We identified 47 families with the early-onset, autosomal-dominant form of diabetes that met the criteria of MODY. Mutation screening involved direct sequencing of the HNF1A gene. Patients' characteristics included clinical data, anthropometric measurements and biochemical parameters. The search for renal malformations involved ultrasound examination of all HNF1A mutation carriers.


RESULTS
We identified 13 HNF1A MODY families and examined 56 mutation carriers, including 46 diabetic patients. The average HbA(1c) level among the diabetics was 7.5%. We identified diabetic retinopathy in 47.7% of the MODY patients, while diabetic nephropathy was present in 25%. In five HNF1A mutation carriers from three families, renal developmental malformations were identified, including one functioning kidney in two (3.6%) of them.


CONCLUSIONS
This first systematic search for HNF1A mutations in a Polish population revealed that they are a frequent cause of MODY. In this population, HNF1A mutation carriers were characterized by a high prevalence of diabetic complications. In addition, renal developmental abnormalities were found in some mutation carriers.
Skupien
J
J
Department of Metabolic Diseases, Jagiellonian University, Medical College, 15, Kopernika Street, 31-501 Krakow, Poland.
Gorczynska-Kosiorz
S
S
Klupa
T
T
Cyganek
K
K
Wanic
K
K
Borowiec
M
M
Sieradzki
J
J
Malecki
M-T
MT
D000005:Abdomen / Q000000981:diagnostic imaging; D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D002096:C-Peptide / Q000097:blood; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000235:genetics*; D006801:Humans; D007668:Kidney / Q000002:abnormalities; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011044:Poland / Q000453:epidemiology; D040641:Quantitative Trait Loci; D012016:Reference Values; D014280:Triglycerides; D014463:Ultrasonography
D001786:Blood Glucose; D002096:C-Peptide; D002784:Cholesterol; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D006442:Glycated Hemoglobin; D051538:Hepatocyte Nuclear Factor 1-alpha; D014280:Triglycerides; C496487:HNF1A protein, human