Bardet-Biedl Syndrome Panel

PLUSbpg-method 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 3–4 weeks. SEQbpg-method 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 3–4 weeks. DEL/DUPbpg-method Targeted Del/Dup (CNV) analysis is used to detect bigger disease causing deletions or duplications from the disease-associated genes. Results in 3–4 weeks.

Test code: KI0201

The Blueprint Genetics Bardet-Biedl Syndrome Panel is an 18 gene test for genetic diagnostics of patients with clinical suspicion of Alström syndrome or Bardet-Biedl syndrome.

The panel covers genes associated with autosomal recessive Bardet-Biedl Syndrome, Alström Syndrome and related disorders. This panel is part of the comprehensive Ciliopathy Panel and Retinal Dystrophy Panel.

About Bardet-Biedl Syndrome

Bardet-Biedl syndrome (BBS) is an important genetic cause of chronic kidney disease with end-stage renal disease (ESRD). It is a multi-system disorder, which consists of obesity, retinal degeneration, cognitive impairment, genitor-urinary tract malformations and polydactyly. Polycystic kidneys are the most likely cause of premature death from the syndrome, combined with complications caused by overweight, including type II diabetes, hypertension and hypercholesterolaemia. Although BBS is considered to be a developmental disorder, the only clues in utero may be hexadactyly and hyperechoic kidneys. The diagnosis is often only established once the vision begins to degrade. Estimated prevalence of BBS is 1-9:1,000,000 and in Europe between 1:125,000 and 1:175,000. Genes associated with BBS code for proteins involved in the development and function of primary cilia and absence or dysfunction of BBS proteins results in ciliary anomalies. Recognition of the clinical picture is important as the diagnosis can be confirmed by molecular analysis, allowing appropriate genetic counseling for family members and possible prenatal diagnosis. Patients with BBS will need multidisciplinary medical care. The renal abnormalities are the main life-threatening manifestations because they can lead to ESRD, requiring renal transplantation. Progressive vision loss, together with moderate intellectual deficit (when present), behavioral anomalies, hypomimia and obesity may affect patient’s social life. Alström syndrome is an autosomal recessive disorder, which shares substantial overlap with Bardet-Biedl syndrome. It is characterised by cone-rod dystrophy, obesity, progressive sensorineural hearing impairment, dilated cardiomyopathy, the insulin resistance syndrome and developmental delay. Over 60% of individuals with Alström syndrome develop cardiac failure as a result of dilated cardiomyopathy at some stage of their lives. Males may have hypogonadotrophic hypogonadism. Renal disease may present as polyuria and polydipsia resulting from a urinary concentrating defect. ESRD can occur as early as the late teens. In contrast to BBS, Alström syndrome is characterised by relative preservation of cognitive function and the absence of polydactyly. Alström syndrome is caused by mutations in the gene ALMS1.

Availability

Results in 3-4 weeks. We do not offer a maternal cell contamination (MCC) test at the moment. We offer prenatal testing only for cases where the maternal cell contamination studies (MCC) are done by a local genetic laboratory. Read more: http://blueprintgenetics.com/faqs/#prenatal

Genes in the Bardet-Biedl Syndrome Panel and their clinical significance
Gene Associated phenotypes Inheritance ClinVar HGMD
ALMS1* Alström syndrome AR 31 281
ARL6 Bardet-Biedl syndrome, Retinitis pigmentosa AR 9 21
BBS1 Bardet-Biedl syndrome AR 19 92
BBS2 Bardet-Biedl syndrome, Retinitis pigmentosa AR 30 84
BBS4 Bardet-Biedl syndrome AR 13 45
BBS5 Bardet-Biedl syndrome AR 10 27
BBS7 Bardet-Biedl syndrome AR 12 36
BBS9 Bardet-Biedl syndrome AR 21 42
BBS10 Bardet-Biedl syndrome AR 23 96
BBS12 Bardet-Biedl syndrome AR 8 59
CEP290* Bardet-Biedl syndrome, Leber congenital amaurosis, Joubert syndrome, Senior-Loken syndrome, Meckel syndrome AR 79 252
IFT172 Retinitis pigmentosa, Short -rib thoracic dysplasia with or without polydactyly, Asphyxiating thoracic dysplasia (ATD; Jeune) AR 18 21
MKKS Bardet-Biedl syndrome, McKusick-Kaufman syndrome AR 13 57
MKS1 Bardet-Biedl syndrome, Meckel syndrome AR 39 47
SDCCAG8 Bardet-Biedl syndrome, Senior-Loken syndrome AR 12 18
TMEM67 Nephronophthisis, COACH syndrome, Joubert syndrome, Meckel syndrome AR 78 138
TRIM32 Bardet-Biedl syndrome, Muscular dystrophy, limb-girdle AR 7 15
TTC8 Bardet-Biedl syndrome, Retinitis pigmentosa AR 5 16

*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 Bardet-Biedl Syndrome Panel that covers classical genes associated with Alström syndrome and Bardet-Biedl 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.

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. Average sensitivity and specificity in Blueprint NGS Panels is 99.3% and 99.9% for detecting SNPs. Sensitivity to for indels vary depending on the size of the alteration: 1-10bps (96.0%), 11-20 bps (88.4%) and 21-30 bps (66.7%). The longest detected indel was 46 bps by sequence analysis. Detection limit for Del/Dup (CNV) analysis varies through the genome depending on exon size, sequencing coverage and sequence content. The sensitivity is 71.5% for single exon deletions and duplications and 99% for three exons’ deletions and duplications. We have validated the assays for different starting materials including EDTA-blood, isolated DNA (no FFPE) and saliva that all provide high-quality results. 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.

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 Bardet-Biedl Syndrome Panel

ICD-10 Disease
Q87.89 Bardet-Biedl syndrome

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.

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