Maturity onset diabetes of the young (MODY) refers to any of several hereditary forms of diabetes caused by mutations in an autosomal dominant gene disrupting insulin production. MODY is often referred to as monogenic diabetes to distinguish it from the more common types of diabetes which involve more complex combinations of causes involving multiple genes and environmental factors. MODY is inherited in an autosomal dominant fashion, and most patients therefore have other members of the family with diabetes; penetrance differs between the types (from 40% to 90%). We provide sequencing analysis for MODY 1-6. We provide testing for the mutations listed below known to be associated with MODY.
||hepatocyte nuclear factor 4α
||Due to a loss-of-function mutation in the HNF4α gene. 5%–10% cases
||Due to any of several mutations in the GCK gene. 30%–70% cases. Mild fasting hyperglycaemia throughout life. Small rise on glucose loading.
||hepatocyte nuclear factor 1α
||Mutations of the HNF1α gene (a homeobox gene). 30%–70% cases. Tend to be responsive to sulfonylureas. Low renal threshold for glucose.
||insulin promoter factor-1
||Mutations of the IPF1 homeobox (Pdx1) gene. < 1% cases. Associated with pancreatic agensis in homozygotes and occasionally in heterozygotes.
||hepatocyte nuclear factor 1β
||One of the less common forms of MODY, with some distinctive clinical features, including atrophy of the pancreas and several forms of renal disease. Defect in HNF-1 beta gene. 5%–10% cases.
||neurogenic differentiation 1
||Mutations of the gene for the transcription factor referred to as neurogenic differentiation 1. Very rare: 5 families reported
Methodology: Sequencing of entire coding region of each gene
Purpose: Confirmation of Clinical Diagnosis
Test Requisition: Sequencing Requisition
MODY 1 HNF4A CPT Code: 81406 Cost: $550.00
MODY 2 GCK CPT Code: 81406 Cost: $550.00
MODY 3 HNF1A CPT Code: 81405 Cost: $550.00
MODY 4 PDX1 CPT Code: 81406 Cost: $550.00
MODY 5 HNF1B CPT Code: 81405 Cost: $550.00
MODY 6 NEUROD1 CPT Code: 81479 Cost: $550.00
Panel CPT Code: 81407 Panel Price: $3300.00
Turn-around-time: 5-6 weeks each test
Del/Dup testing also available for each gene, except HNF1A, at a cost of $600.00 per gene
1. What is maturity-onset diabetes of the young (MODY)?". National Diabetes Information Clearinghouse (NDIC) (National Institute of Diabetes and Digestive and Kidney Diseases, NIH). Retrieved 2008-07-29.
2. Barry J. Goldstein; Dirk Müller-Wieland (2008). Type 2 diabetes: principles and practice. CRC Press. pp. 529–.
3. Yorifuji, T; Kurokawa, K; Mamada, M; Imai, T; Kawai, M; Nishi, Y; Shishido, S; Hasegawa, Y; Nakahata, T (2004 Jun). "Neonatal diabetes mellitus and neonatal polycystic, dysplastic kidneys: Phenotypically discordant recurrence of a mutation in the hepatocyte nuclear factor-1beta gene due to germline mosaicism.". The Journal of clinical endocrinology and metabolism 89 (6): 2905–8
4. Edghill, EL; Bingham, C; Slingerland, AS; Minton, JA; Noordam, C; Ellard, S; Hattersley, AT (2006 Dec). "Hepatocyte nuclear factor-1 beta mutations cause neonatal diabetes and intrauterine growth retardation: support for a critical role of HNF-1beta in human pancreatic development.". Diabetic medicine : a journal of the British Diabetic Association 23 (12): 1301–6.
5. Poretsky, L (December 2008). Principles of Diabetes Mellitus. Springer. pp. 221–.
6. Naylor R, Philipson LH (2011). "Who should have genetic testing for maturity-onset diabetes of the young?" Clin Endocrinol(Oxf) 75(4):422-6. doi: 10.1111/j.1365-2265.2011.04049.x.