Diagnostic Use
For the diagnosis of monogenic diabetes.
Important Note:
All genetic test requests for MODY require a referral from an endocrinologist. All MODY referrals also require completed Monogenic Diabetes Referral form.
Failure to provide the forms required above may delay testing.
Predictive testing only through Endocrinology or Genetic Services.
See link for MODY referral form below.
Reference Intervals
TARGET GENES AND COVERAGE: The coding regions and flanking +/-20bp (encompassing the splice sites) of the following listed genes are sequenced in this test. 100% coverage of bases within these regions is achieved by NGS (to a depth of ?50x).
|
Gene
|
Reference Sequences
|
| ABCC8* |
NM_000352.6, NP_000343.2 |
| AKT2 |
NM_001626.6, NP_001617.1 |
| APPL1 |
NM_012096.3, NP_036228.1 |
| CEL |
NM_001807.6, NP_001798.3 |
| CIDEC |
NM_001321142.2, NP_001308071.1 |
| CISD2 |
NM_001008388.5, NP_001008389.1 |
| DCAF17 |
NM_025000.4, NP_079276.2 |
| DNAJC3 |
NM_006260.5, NP_006251.1 |
| DUT |
NM_001025248.2, NP_001020419.1 |
| DYRK1B |
NM_004714.3, NP_004705.1 |
| GATA4* |
NM_001308093.3, NP_001295022.1 |
| GATA6 |
NM_005257.6, NP_005248.2 |
| GCK* |
NM_000162.5, NP_000153.1 |
| GLUD1 |
NM_005271.5, NP_005262.1 |
| HNF1A* |
NM_000545.8, NP_000536.6 |
| HNF1B |
NM_000458.4, NP_000449.1 |
| HNF4A* |
NM_175914.5, NP_787110.2 |
| INS* |
NM_000207.3, NP_000198.1 |
| INSR |
NM_000208.4, NP_000199.2 |
| KCNJ11* |
NM_000525.4, NP_000516.3 |
| LIPE |
NM_005357.4, NP_005348.2 |
| LMNA* |
NM_170707.4, NP_733821.1 |
| MAFA |
NM_201589.4, NP_963883.2 |
| MANF |
NM_006010.6, NP_006001.5 |
| NEUROD1* |
NM_002500.5, NP_002491.3 |
| PAX6* |
NM_001368894.2, NP_001355823.1 |
| PCBD1 |
NM_000281.4, NP_000272.1 |
| PDX1 |
NM_000209.4, NP_000200.1 |
| PIK3R1 |
NM_181523.3, NP_852664.1 |
| PLIN1 |
NM_002666.5, NP_002657.3 |
| POLD1 |
NM_002691.4, NP_002682.2 |
| PPARG |
NM_138711.6, NP_619725.3 |
| PPP1R15B |
NM_032833.5, NP_116222.4 |
| RFX6 |
NM_173560.4, NP_775831.2 |
| SLC29A3 |
NM_018344.6, NP_060814.4 |
| TRMT10A |
NM_001134665.3, NP_001128137.1 |
| WFS1 |
NM_006005.3, NP_005996.2 |
| ZBTB20 |
NM_001348800.3, NP_001335729.1 |
| ZFP57 |
NM_001109809.5, NP_001103279.2 |
| ZMPSTE24 |
NM_005857.5, NP_005848.2 |
|
Mitochondrial variants
|
m.12258C>A, m.12271T>C, m.14684C>T, m.14709T>C, m.3243A>G, m.8344A>G |
* Genes marked with an asterisk have additional non-coding regions analysed
Test Method
Capture-based target enrichment is performed using the Twist Bioscience Enzymatic Fragmentation Library Preparation v1.0 and custom panel. Next-generation sequencing (NGS) is performed on an Illumina MiSeq platform. Variant calls are identified using the Illumina DRAGEN analysis platform v4.0.3. Variant triage and curation is performed using Agilent Alissa Interpret. The Multiplex Ligation-dependent Probe Amplification (MLPA) kit P241-E1 MODY Mix1 from MRC-Holland was used to detect copy number variations in HNF4A, GCK, HNF1A, and HNF1B.
Uncertainty of Measurement
Please contact the Diagnostic Genetics Pathologist at dgen@adhb.govt.nz to discuss sources of test uncertainty, which include, but are not limited to, measurement uncertainty (MU) and biological variation.