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.
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
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.
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 form - Monogenic Diabetes Molecular Genetics Test Form.pdf
Transport all bloods between 8 and 24 degrees Celsius within 24-48 hours. If necessary specimens can be refrigerated overnight for transport at the temperatures stated above the following day.
For testing of other sample types please contact the laboratory prior to sending.