Congenital Hepatic Fibrosis 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: GA0101

The Blueprint Genetics Congenital Hepatic Fibrosis Panel is a 29 gene test for genetic diagnostics of patients with clinical suspicion of autosomal recessive polycystic kidney and liver disease, Bardet-Biedl syndrome or Joubert syndrome.

Congenital Hepatic Fibrosis Panel cover genes that are mostly causing autosomal recessive disease but X-linked dominant inheritance is observed in association OFD1 mutations, and autosomal dominant inheritance is probably related to PKD2 and digenic inheritance has been observed rarely in BBS1 related disease.

About Congenital Hepatic Fibrosis

Congenital hepatic fibrosis (CHF) is a rare, mostly autosomal recessive condition that presents at birth and affects the liver. CHF rarely occurs as an isolated problem, and is usually associated with ciliopathy syndromes that affect the kidneys. In many cases gross malformations are phenotypically pathognomonic such such as anencephaly in Meckel syndrome and the liver fibrosis is only minor feature along the main findings. The ciliopathy syndromes with hepatic fibrosis include Bardet-Biedl syndrome and Joubert syndrome. In contrast to ciliopathies, polycystic kidney disease is relatively isolated disease with liver cysts and hepatic fibrosis present regularly. Typical liver abnormalities include an enlarged liver, portal hypertension and hepatic fibrosis. Gastrointestinal bleeding, splenomegaly and hypersplenism along low platelet count may be present already at an early phase of the disease. Prevalence of Bardet-Biedl syndrome is 1:13,500-140,000, Joubert syndrome 1:80,000-100,000 and autosomal recessive polycystic kidney and liver disease 1:10,000-40,000.

Availability

Results in 3-4 weeks.

Genes in the Congenital Hepatic Fibrosis Panel and their clinical significance
GeneAssociated phenotypesInheritanceClinVarHGMD
AHI1Joubert syndromeAR4770
ARL6Bardet-Biedl syndrome, Retinitis pigmentosaAR921
ARL13BJoubert syndromeAR97
BBS1Bardet-Biedl syndromeAR1992
BBS2Bardet-Biedl syndrome, Retinitis pigmentosaAR3084
BBS4Bardet-Biedl syndromeAR1345
BBS5Bardet-Biedl syndromeAR1027
BBS7Bardet-Biedl syndromeAR1236
BBS9Bardet-Biedl syndromeAR2142
BBS10Bardet-Biedl syndromeAR2396
BBS12Bardet-Biedl syndromeAR859
CC2D2ACOACH syndrome, Joubert syndrome, Meckel syndromeAR6480
CEP290*Bardet-Biedl syndrome, Leber congenital amaurosis, Joubert syndrome, Senior-Loken syndrome, Meckel syndromeAR79252
INVSNephronophthisisAR933
IQCB1Senior-Loken syndromeAR1535
MKKSBardet-Biedl syndrome, McKusick-Kaufman syndromeAR1357
MKS1Bardet-Biedl syndrome, Meckel syndromeAR3947
NPHP1Nephronophthisis, Joubert syndrome, Senior-Loken syndromeAR1264
NPHP3Nephronophthisis, Renal-hepatic-pancreatic dysplasia, Meckel syndromeAR2071
NPHP4Nephronophthisis, Senior-Loken syndromeAR10104
OFD1Simpson-Golabi-Behmel syndrome, Retinitis pigmentosa, Orofaciodigital syndrome, Joubert syndromeXL129148
PKD2Polycystic kidney diseaseAD14261
PKHD1Polycystic kidney diseaseAR73522
RPGRIP1LCOACH syndrome, Joubert syndrome, Meckel syndrome, Retinal degeneration in ciliopathy, modifierAD/AR2841
TMEM67Nephronophthisis, COACH syndrome, Joubert syndrome, Meckel syndromeAR78138
TRIM32Bardet-Biedl syndrome, Muscular dystrophy, limb-girdleAR715
TTC8Bardet-Biedl syndrome, Retinitis pigmentosaAR516
TTC21BShort-rib thoracic dysplasia, NephronophthisisAR647
WDR35AR1524
  • * 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 hepatic fibrosis panel that covers classical genes associated with autosomal recessive polycystic kidney and liver disease, Bardet-Biedl syndrome, COACH syndrome, Joubert syndrome and nephronophthisis. 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 Hepatic Fibrosis Panel

ICD-10Disease
Q87.89Bardet-Biedl syndrome
Q04.3Joubert syndrome
Q61.1Autosomal recessive polycystic kidney and liver disease

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.