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Maturity onset diabetes of the young - MODY 1, 2, 3 and 5
Short Description : MODY 1, 2, 3 & 5 genetic testing


DNA/RNA
Test performed by: LabPLUS - Dept. Diagnostic Genetics - Molecular Genetics


Referral Requirements

Important Note:

All genetic test requests for MODY require a referral from an endocrinologist. All MODY referrals also require completed NZSSD forms A and B (as well as forms C through to F if appropriate).

Referrals requiring the 34 gene panel at Exeter Lab in the UK will also need a completed Exeter MODY referral form.

Failure to provide the forms required above may delay testing.

Predictive testing only through Endocrinology or Genetic Services.


Contacts:

Endocrinology can be contacted on (09) 307 4949 ext. 26850.

Genetic Health Service NZ can be contacted on 0800 476 123.

 

Download: MODY referral information and forms - Monogenic_diabetes_card_with_forms_May 18.pdf

Download: Referral form for sendaway MODY testing to Exeter lab in the UK - Exeter MODY referral form.pdf


Specimen Collection
EDTA4 mL Paediatric EDTA Blood (Preferred)

Note:

For paediatric samples a minimum of 0.5ml blood EDTA can be processed. (Microcollect)

Transport all bloods at room temperature within 24-48 hours. If necessary specimens can be refrigerated overnight for transport at room temperature the following day.

For testing of other sample types please contact the laboratory prior to sending.


EDTA8 mL Adult EDTA Blood
Turnaround Time: Within 13 weeks
Contact Information

Contact Molecular Genetics via:

Lablink                                                     ext 22000

Mark Greenslade (Technical Head)   ext 22010

Pippa Grainger (Section leader)              ext 22014

Email: DGen@adhb.govt.nz




Background Information

Maturity-onset diabetes of the young (MODY) describes the dominantly inherited disorder of non-insulin-dependent diabetes typically diagnosed before 25 years that was first recognised by Tattersall. MODY is the most common form of monogenic diabetes, accounting for an estimated 1-2% of diabetes in Europe, but is often misdiagnosed as type 1 or type 2 diabetes. MODY accounts for up to 5% of noninsulin-dependent (type 2) diabetes.


The term MODY is used to describe a group of clinically heterogeneous, often non-insulin-dependent forms of diabetes that are defined at the molecular genetics level by mutations in at least six genes: hepatic nuclear factor 4 a (MODY1), glucokinase (MODY2), hepatic nuclear factor 1a (MODY3), insulin promoter factor 1 (MODY4), hepatic nuclear factor 1b (MODY5), and neurogenic differentiation factor-1 (MODY 6). All show dominant inheritance and are disorders of beta cell dysfunction, but variable features include the age at onset, severity of the hyperglycaemia (and hence risk of complications) and associated clinical features.

Mutations in the GCK and HNF1a genes are the most frequent cause of MODY in all populations studied. They account for approximately 70% of cases. The ratio of GCK to HNF1a mutations varies between countries because of different recruitment strategies for genetic testing; blood glucose screening in young, asymptomatic individuals will identify a higher proportion of GCK mutations.

Mutations identified in the GCK , HNF1a and HNF4a genes include missense, nonsense, splicing, small deletions/ insertions/duplications, and splice site and promoter region mutations. The location of mutations within the HNF1a gene influences the age at diagnosis; the average age at diagnosis for patients with exon 1-6 mutations that affect all three HNF1A isoforms is younger than for those with mutations in exons 8-10 that affect only isoform HNF1A(A).

A molecular genetic diagnosis of a GCK , HNF1a or HNF4a mutation is important because it confirms a diagnosis of MODY, classifies the subtype, predicts the likely clinical course and may change the patient's treatment.

The 'renal cysts and diabetes syndrome' (MODY5) is an autosomal dominant disorder caused by mutations in HNF1b . This comprises(1) nondiabetic renal disease resulting from abnormal renal development, and (2) diabetes, which in some cases occurs earlier than age 25 years and is thus consistent with a diagnosis of maturity-onset diabetes of the young (MODY). The renal disease is highly variable and includes renal cysts, glomerular tufts, aberrant nephrogenesis, primitive tubules, irregular collecting systems, oligomeganephronia, enlarged renal pelves, abnormal calyces, small kidney, single kidney, horseshoe kidney, and hyperuricemic nephropathy. Affected individuals may also have abnormalities of the genital tract, including vaginal aplasia, rudimentary uterus, bicornuate uterus, epididymal cysts, and atresia of the vas deferens.

Molecular genetic testing for HNF4a , GCK , HNF1a and HNF1b is available.

For more information about the Molecular Genetics service:

Molecular Genetics information page


Last updated at 15:49:04 22/03/2021