Cutis Laxa Panel
Test code: DE0501
The Blueprint Genetics Cutis Laxa Panel is an eight gene test for genetic diagnostics of patients with clinical suspicion of arterial tortuosity or cutis laxa.
It has usually autosomal recessive (AR) inheritance although autosomal dominant pattern is observed in ELN related cutis laxa and some AR genes (ALDH18A1 and FBLN5) associate also to dominant disease.
About Cutis Laxa
Cutis laxa is a group of connective tissue disorder where loose or lax skin is common feature leading to sagging of the skin and a droopy appearance of the face. Cutis laxa may also affect heart, blood vessels, joints, intestines and lungs. Cardiovascular involvement includes arterial tortuosity, aneurysms and aortic stenosis. Inguinal and umbilical hernias as well as bladder diverticula are relatively common. Some people with cutis laxa develop emphysema during childhood especially when EFEMP2 or FBLN5 is defective. In general, the autosomal recessive forms of cutis laxa (ARCL) tend to be more severe than the autosomal dominant form. Aneurysms are more frequent in EFEMP2 and SLC2A10 related cutis laxa whereas developmental delay in ALDH18A1, ATP6V0A2and PYCR1. Clinical manifestations associated with EFEMP2 mutations are highly variable and some patients even die prenatally or shortly after birth due to cardiopulmonary complications. In addition to the features described above, some people with ARCL may lose the ability to walk by adolescence even though the skin condition may improve over time. Wrinkly skin syndrome is an allelic disorder to ARCL but is a relatively mild disorder presenting with reduced skin elasticity, dental abnormalities and delayed closure of the fontanel. Cutis laxa may be part of the syndrome called Macrocephaly, Alopecia, Cutis laxa and Scoliosis (MACS), in which the progressive facial coarsening, gingival hypertrophy and joint hyperlaxity may also be present. The X-linked form of cutis laxa is often called occipital horn syndrome. This form of the disorder is considered a mild type of Menkes syndrome. In addition to characteristic skin changes, occipital horn syndrome presents with wedge-shaped calcium deposits in a bone at the base of the skull, coarse hair and loose joints.
Results in 3-4 weeks.
|ALDH18A1||Spastic paraplegia, Cutis laxa||AD/AR||18||25|
|ATP6V0A2||Cutis laxa, Wrinkly skin syndrome||AR||16||52|
|ELN||Cutis laxa, Supravalvular aortic stenosis||AD||67||104|
|FBLN5||Cutis laxa, Macular degeneration, age-related||AD/AR||13||21|
|SLC2A10||Arterial tortuosity syndrome||AR||21||30|
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 cutis laxa panel that covers classical genes associated with arterial tortuosity, cutis laxa and wrinkly skin 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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Choose an analysis method
ICD & CPT codes
Commonly used ICD-10 codes when ordering the Cutis Laxa Panel
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.