Congenital Adrenal Hyperplasia 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: EN0801

The Blueprint Genetics Congenital Adrenal Hyperplasia Panel is a seven gene test for genetic diagnostics of patients with clinical suspicion of congenital adrenal hyperplasia or congenital adrenogenital disorders associated with enzyme deficiency.

The panel covers genes associated with autosomal recessive (CYP21A2) and autosomal dominant forms of the disease.

About Congenital Adrenal Hyperplasia

Congenital adrenal hyperplasia (CAH) is an inherited disorder of steroidogenesis characterized by adrenal insufficiency and variable degrees of hyper or hypo androgeny manifestations, depending of the type and the severity of the disease. A classic form presents with prenatal onset of virilization caused by severe enzyme deficiency and is distinguished from a non-classic form with mild enzyme deficiency and postnatal onset. The most frequent form of classical CAH is 21-hydroxylase deficiency (21-OHD), which can further be divided into simple virilizing form (~25% of affected individuals) and the salt-wasting form, in which aldosterone production is inadequate (≥75% of individuals). Newborns with salt-wasting 21-OHD CAH are at risk for life-threatening salt-wasting crises. Individuals with the non-classic form of 21-OHD CAH present postnatally with signs of hyperandrogenism; females with the non-classic form are not virilized at birth. In 90-95% of cases, CAH is caused by a mutation in the CYP21A2 gene. Mutations in the CYP11B1 gene is the second most common cause of CAH. The estimated prevalence of classic CAH is 1:10,000 and annual incidence ranges from 1:5,000 to 1:15,000. The prevalence of non-classic 21-OHD CAH in the general heterogeneous population of New York City was estimated as high as 1:100. The highest ethnic-specific non-classic disease prevalence (1:27) is found among Ashkenazi Jews. Other ethnic groups exhibiting high non-classic disease prevalence are: Hispanics (1:40), Slavs (1:50) and Italians (1:300).

Availability

Results in 3-4 weeks.

Genes in the Congenital Adrenal Hyperplasia Panel and their clinical significance
GeneAssociated phenotypesInheritanceClinVarHGMD
CYP11B1*Adrenal hyperplasia, congenital, due to 11-beta-hydroxylase deficiency, Glucocorticoid-remediable aldosteronismAD/AR23142
CYP17A1Adrenal hyperplasia, congenital, due to 17-alpha-hydroxylase deficiencyAR32123
CYP21A2*Adrenal hyperplasia, congenital, due to 21-hydroxylase deficiencyAR41288
HSD3B23-beta-hydroxysteroid dehydrogenase, II deficiencyAR1057
PORDisordered steroidogenesis due to cytochrome p450 oxidoreductase deficiencyAR1284
PRKAR1AMyxoma, intracardiac, Acrodysostosis, Pigmented nodular adrenocortical disease, Carney complexAD50173
STARLipoid adrenal hyperplasiaAR1577
  • * Some regions of the gene are duplicated in the genome leading to limited sensitivity within the regions. Thus, low-quality variants are filtered out from the duplicated regions and only high-quality variants confirmed by other methods are reported out. Read more.

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 congenital adrenal hyperplasia panel that covers classical genes associated with congenital adrenal hyperplasia and congenital adrenogenital disorders associated with enzyme deficiency. 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 Congenital Adrenal Hyperplasia Panel

ICD-10Disease
E25.0Congenital adrenal hyperplasia
E25.0Congenital adrenogenital disorders associated with enzyme deficiency

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.