Arthrogryposes 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: MA0501

The Blueprint Genetics Arthrogryposes Panel is a 58 gene test for genetic diagnostics of patients with clinical suspicion of arthrogryposis.

Arthrogryposes are a group of disorders that involve congenital joint contractures. This comprihensive panel includes Fetal Akinesia Deformation Sequence / LMPS / Related Disorder Panel and covers, but is not limited to the disrders covered by the subpanels. This panel enables effective differential diagnostics of arthrogryposes and associated diseases. The Panel is also part of Comprehensive Skeletal / Malformation Syndrome Panel.

About Arthrogryposes

Arthrogryposis (also known as arthrogryposis multiplex congenital, AMC) are characterized by congenital contractures of 2 or more different body areas without a primary neurologic or muscle disease. Children born with joint contractures have abnormal fibrosis of the muscle tissue causing muscle shortening, and therefore are unable to perform passive extension and flexion in the affected joints. Arthrogryposis has been divided into three groups: amyoplasia, distal arthrogryposis, and syndromic. Amyoplasia is characterized by severe joint contractures and muscle weakness, distal arthrogryposis mainly involves the hands and feet, and syndromic group consists of types of arthrogryposis with a primary neurological or muscle disease. 70-80% of the cases of arthrogryposis are caused by neurological abnormalities and most types that have primary neurological or muscle disease result from an underlying genetic syndrome. More than 35 specific genetic disorders associated with arthrogryposis have been described.

Availability

Results in 3-4 weeks.

Genes in the Arthrogryposes Panel and their clinical significance
GeneAssociated phenotypesInheritanceClinVarHGMD
ACTA1MyopathyAD/AR34201
AGRNMyasthenic syndrome, congenitalAR1010
BIN1Myopathy, centronuclearAR615
CASKMental retardation and microcephaly with pontine and cerebellar hypoplasia, FG syndrome, Mental retardationXL4380
CFL2Nemaline myopathyAR23
CHATMyasthenic syndrome, congenitalAR1468
CHRNA1Myasthenic syndrome, congenitalAD/AR1932
CHRNB1Myasthenic syndromeAD/AR58
CHRNDMyasthenic syndromeAD/AR1219
CHRNEMyasthenic syndromeAD/AR26121
CHRNGMultiple pterygium syndrome, Escobar syndromeAR1129
CHST14Ehlers-Danlos syndrome, musculocontracturalAR1021
COL6A2Epilepsy, progressive myoclonic, Bethlem myopathy, Myosclerosis, congenital, Ullrich congenital muscular dystrophyAD/AR65134
COLQMyasthenic syndrome, congenitalAR1266
DHCR24DesmosterolosisAR68
DOK7Myasthenic syndrome, congenitalAR1568
DPAGT1Congenital disorder of glycosylation, Myasthenic syndrome, congenitalAR1228
ECEL1ArthrogryposisAR1827
EGR2Neuropathy, Dejerine-Sottas disease, Charcot-Marie-Tooth diseaseAD/AR1223
ERCC5Xeroderma pigmentosum, Xeroderma pigmentosum/Cockayne syndromeAR1751
ERCC6Xeroderma Pigmentosum-Cockayne Syndrome, De Sanctis-Cacchione syndromeAD/AR3791
EXOSC3Pontocerebellar hypoplasiaAR918
FBN2Congenital contractural arachnodactyly (Beals syndrome)AD3085
FHL1*Myopathy with postural muscle atrophy, Emery-Dreifuss muscular dystrophy, Reducing bod myopathyXL1847
FKTNMuscular dystrophy-dystroglycanopathy, Dilated cardiomyopathy (DCM), Muscular dystrophy-dystroglycanopathy (limb-girdle)AD/AR2851
GBA*Gaucher diseaseAR73446
GBE1Glycogen storage diseaseAR2569
GFPT1Myasthenic syndrome, congenitalAR633
GLE1Lethal congenital contracture syndrome, Arthrogryposis, lethal, with anterior horn cell diseaseAR49
KAT6BOhdo syndrome, SBBYS variant, Genitopatellar syndromeAD2353
KLHL40Nemaline myopathyAR524
MPZNeuropathy, Roussy-Levy syndrome, Dejerine-Sottas disease, Charcot-Marie-Tooth diseaseAD74235
MTM1Myopathy, centronuclearXL152284
MUSKMyasthenic syndrome, congenitalAR1017
MYBPC1Arthrogryposis, Lethal congenital contractural syndromeAD/AR47
MYH2Inclusion body myopathyAD1020
MYH3ArthrogryposisAD1431
NALCNNeuroaxonal neurodegeneration, infantile, with facial dysmophism, Congenital contractures of the limbs and face, hypotonia, and developmental delayAD/AR2328
NEB*Nemaline myopathyAR34262
PIEZO2*Marden-Walker syndrome, Distal arthrogryposisAD2124
PLOD2Bruck syndromeAR411
PMM2Congenital disorder of glycosylationAR37119
RAPSNMyasthenic syndrome, congenitalAR1857
RARS2Pontocerebellar hypoplasiaAR1730
SCO2Leigh syndrome, Hypertrophic cardiomyopathy (HCM), Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency, MyopiaAD/AR1732
SELENONMuscular dystrophy, rigid spine, Myopathy, congenital, with fiber- disproportionAR1650
TGFB3Loeys-Dietz syndrome (Reinhoff syndrome), Arrhythmogenic right ventricular dysplasiaAD818
TK2Mitochondrial DNA depletion syndromeAR3844
TNNI2Arthrogryposis multiplex congenitaAD411
TNNT1Nemaline myopathyAR25
TPM2CAP myopathy, Nemaline myopathy, Arthrogryposis, distalAD1137
TPM3*CAP myopathy, Nemaline myopathy, Myopathy, congenital, with fiber- disproportionAD1826
TRPV4Metatropic dysplasia, Spondyloepiphyseal dysplasia Maroteaux type, Parastremmatic dwarfism, Hereditary motor and sensory neuropathy, Spondylometaphyseal dysplasia Kozlowski type, Spinal muscular atrophy, Charcot-Marie-Tooth diseaseAD5371
TSEN2Pontocerebellar hypoplasiaAR64
TSEN54Pontocerebellar hypoplasiaAR1620
VPS33BArthrogryposis - renal dysfunction - cholestasisAD/AR953
VRK1Pontocerebellar hypoplasiaAR68
ZBTB42Lethal congenital contracture syndromeAR11
  • * 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 arthrogryposes panel that covers classical genes associated with arthrogryposis. 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 Arthrogryposes Panel

ICD-10Disease
Q74.3Arthrogryposis

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.