MODY Panel

SEQmethod-seq-icon Our Sequence Analysis is based on a proprietary targeted sequencing method OS-Seq™ and offers panels targeted for genes associated with certain phenotypes. A standard way to analyze NGS data for finding the genetic cause for Mendelian disorders. Results in 21 days. DEL/DUPmethod-dup-icon Targeted Del/Dup (CNV) analysis is used to detect bigger disease causing deletions or duplications from the disease-associated genes. Results in 21 days. PLUSmethod-plus-icon Plus Analysis combines Sequence + Del/Dup (CNV) Analysis providing increased diagnostic yield in certain clinical conditions, where the underlying genetic defect may be detectable by either of the analysis methods. Results in 21 days.

Test code: EN0601

The Blueprint Genetics MODY Panel is a 12 gene test for genetic diagnostics of patients with clinical suspicion of maturity-onset diabetes of the young.

The panel covers genes associated with autosomal dominant forms of the disease.

About MODY

Maturity-onset diabetes of the young (MODY) is an autosomal dominant inherited form of diabetes, which accounts for 1–2% of of individuals with diabetes. MODY is a rare clinically and genetically heterogeneous form of diabetes characterized by young age of onset (generally 10-45 years of age), with development of non-insulin dependent diabetes prior to 25 years of age. Additionally, blood vessel abnormalities of the retinas (retinopathy) and kidneys, and congenital abnormalities due to diabetes complications have also been noted. Individuals with MODY typically have no reported history of obesity or metabolic syndrome accompanying hyperglycemia. Many people with MODY are misdiagnosed with type 1 or type 2 diabetes. It is the most common form of monogenic diabetes with estimated prevalence at 1:10,000 in adults and 1:23,000 in children. Around 80% of cases are misdiagnosed as type 1 or type 2 diabetes, complicating prevalence and incidence estimations. Genetic testing is generally pursued only in those with classic features of MODY. However, only 50% of subjects with genetically diagnosed MODY meet classic criteria. Establishing a diagnosis of MODY significantly impacts clinical management. Heterozygous mutations in three genes, HNF1A, HNF4A, and GCK, together account for >90% of all MODY with a known genetic cause. Patients with HNF1A and HNF4A mutations have slowly progressing beta-cell dysfunction, and treatment with low-dose sulfonylurea results in stable or improved glycemic control and improved quality of life related to diabetes care compared with insulin or metformin therapy. GCK-MODY has a unique phenotype of mild, nonprogressive hyperglycemia, with HbA1c typically <7% (53 mmol/mol). It is not associated with increased risk of microvascular and macrovascular complications seen in other forms of diabetes. Generally, treatment does not change HbA1c. Molecular diagnosis of GCK-MODY allows pharmacologic therapy to be discontinued and decreases the needed frequency of medical surveillance. (PMID: 24026547).

Availability

Results in 3-4 weeks.

Genes in the MODY Panel and their clinical significance
GeneAssociated phenotypesInheritanceClinVarHGMD
ABCC8Hyperinsulinemic hypoglycemia, Diabetes, permanent neonatal, Hypoglycemia, leucine-induced, Diabetes mellitus, transient neonatalAD/AR78601
BLKMaturity onset diabetes of the youngAD415
GCKHyperinsulinemic hypoglycemia, familial, Diabetes mellitus, permanent neonatalAD/AR118774
HNF1AMaturity onset diabetes of the young, Renal cell carcinoma, nonpapillary clear cell, Liver adenomatosisAD47505
HNF1BRenal cell carcinoma, nonpapillary chromophobe, Renal cysts and diabetes syndromeAD27194
HNF4ACongenital hyperinsulinism, diazoxide-responsive, Maturity onset diabetes of the young, Fanconi renotubular syndrome 4 with maturity-onset diabetes of the youngAD19145
INSDiabetes mellitus, permanent neonatalAD3274
KCNJ11Hyperinsulinemic hypoglycemia, Diabetes, permanent neonatal, Diabetes mellitus, transient neonatalAD/AR49171
KLF11Maturity onset diabetes of the youngAD15
NEUROD1Maturity onset diabetes of the youngAD315
PAX4Diabetes mellitusAD312
PDX1Pancreatic agenesis, Neonatal diabetes mellitusAR1029

Gene, refers to HGNC approved gene symbol; Inheritance to inheritance patterns such as autosomal dominant (AD), autosomal recessive (AR) and X-linked (XL); ClinVar, refers to a number of variants in the gene classified as pathogenic or likely pathogenic in ClinVar (http://www.ncbi.nlm.nih.gov/clinvar/); HGMD, refers to a number of variants with possible disease association in the gene listed in Human Gene Mutation Database (HGMD, http://www.hgmd.cf.ac.uk/ac/). The list of associated (gene specific) phenotypes are generated from CDG (http://research.nhgri.nih.gov/CGD/) or Orphanet (http://www.orpha.net/) databases.

Blueprint Genetics offers a comprehensive MODY panel that covers classical genes associated with maturity-onset diabetes of the young and renal cysts and diabetes syndrome. The genes are carefully selected based on the existing scientific evidence, our experience and most current mutation databases. Candidate genes are excluded from this first-line diagnostic test. The test does not recognise balanced translocations or complex inversions, and it may not detect low-level mosaicism. The test should not be used for analysis of sequence repeats or for diagnosis of disorders caused by mutations in the mitochondrial DNA.

Please see our latest validation report showing sensitivity and specificity for SNPs and indels, sequencing depth, % of the nucleotides reached at least 15x coverage etc. If the Panel is not present in the report, data will be published when the Panel becomes available for ordering. Analytical validation is a continuous process at Blueprint Genetics. Our mission is to improve the quality of the sequencing process and each modification is followed by our standardized validation process. All the Panels available for ordering have sensitivity and specificity higher than > 0.99 to detect single nucleotide polymorphisms and a high sensitivity for indels ranging 1-19 bp. The diagnostic yield varies substantially depending on the used assay, referring healthcare professional, hospital and country. Blueprint Genetics’ Plus Analysis (Seq+Del/Dup) maximizes the chance to find molecular genetic diagnosis for your patient although Sequence Analysis or Del/Dup Analysis may be cost-effective first line test if your patient’s phenotype is suggestive for a specific mutation profile. Detection limit for Del/Dup analysis varies through the genome from one to six exon Del/Dups depending on exon size, sequencing coverage and sequence content.

The sequencing data generated in our laboratory is analyzed with our proprietary data analysis and annotation pipeline, integrating state-of-the art algorithms and industry-standard software solutions. Incorporation of rigorous quality control steps throughout the workflow of the pipeline ensures the consistency, validity and accuracy of results. The highest relevance in the reported variants is achieved through elimination of false positive findings based on variability data for thousands of publicly available human reference sequences and validation against our in-house curated mutation database as well as the most current and relevant human mutation databases. Reference databases currently used are the 1000 Genomes Project (http://www.1000genomes.org), the NHLBI GO Exome Sequencing Project (ESP; http://evs.gs.washington.edu/EVS), the Exome Aggregation Consortium (ExAC; http://exac.broadinstitute.org), ClinVar database of genotype-phenotype associations (http://www.ncbi.nlm.nih.gov/clinvar) and the Human Gene Mutation Database (http://www.hgmd.cf.ac.uk). The consequence of variants in coding and splice regions are estimated using the following in silico variant prediction tools: SIFT (http://sift.jcvi.org), Polyphen (http://genetics.bwh.harvard.edu/pph2/), and Mutation Taster (http://www.mutationtaster.org).

Through our online ordering and statement reporting system, Nucleus, the customer can access specific details of the analysis of the patient. This includes coverage and quality specifications and other relevant information on the analysis. This represents our mission to build fully transparent diagnostics where the customer gains easy access to crucial details of the analysis process.

In addition to our cutting-edge patented sequencing technology and proprietary bioinformatics pipeline, we also provide the customers with the best-informed clinical report on the market. Clinical interpretation requires fundamental clinical and genetic understanding. At Blueprint Genetics our geneticists and clinicians, who together evaluate the results from the sequence analysis pipeline in the context of phenotype information provided in the requisition form, prepare the clinical statement. Our goal is to provide clinically meaningful statements that are understandable for all medical professionals, even without training in genetics.

Variants reported in the statement are always classified using the Blueprint Genetics Variant Classification Scheme modified from the ACMG guidelines (Richards et al. 2015), which has been developed by evaluating existing literature, databases and with thousands of clinical cases analyzed in our laboratory. Variant classification forms the corner stone of clinical interpretation and following patient management decisions. Our statement also includes allele frequencies in reference populations and in silico predictions. We also provide PubMed IDs to the articles or submission numbers to public databases that have been used in the interpretation of the detected variants. In our conclusion, we summarize all the existing information and provide our rationale for the classification of the variant.

A final component of the analysis is the Sanger confirmation of the variants classified as likely pathogenic or pathogenic. This does not only bring confidence to the results obtained by our NGS solution but establishes the mutation specific test for family members. Sanger sequencing is also used occasionally with other variants reported in the statement. In the case of variant of uncertain significance (VUS) we do not recommend risk stratification based on the genetic finding. Furthermore, in the case VUS we do not recommend use of genetic information in patient management or genetic counseling. For some cases Blueprint Genetics offers a special free of charge service to investigate the role of identified VUS.

We constantly follow genetic literature adapting new relevant information and findings to our diagnostics. Relevant novel discoveries can be rapidly translated and adopted into our diagnostics without delay. These processes ensure that our diagnostic panels and clinical statements remain the most up-to-date on the market.

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ICD & CPT codes

CPT codes

SEQ81479
DEL/DUP81479


ICD codes

Commonly used ICD-10 codes when ordering the MODY Panel

ICD-10Disease
E11.9Maturity-onset diabetes of the young

Accepted sample types

  • EDTA blood, min. 1 ml
  • Purified DNA, min. 5μg
  • Saliva (Oragene DNA OG-500 kit)

Label the sample tube with your patient’s name, date of birth and the date of sample collection.

Note that we do not accept DNA samples isolated from formalin-fixed paraffin-embedded (FFPE) tissue.