Neuromuscular Disorder Panels

Posted on by Melanie Pepin

The Neuromuscular Disorder Panels include genes that have been identified to be responsible for:
(Click link for gene list)

Spinal Muscular Atrophy

Charcot-Marie-Tooth and Neuropathies

Myopathies/Myotonia, Muscular Dystrophies and Limb Girdle Muscular Dystrophies

Myasthenic Syndromes and Arthrogryposis

Metabolic Myopathies Panel

Chronic Myopathies and Walker Warburg Syndrome

For the above panels order testing on any or all of the phenotypes relevant to your patient.  If none of the panels fit your testing needs, select up to six phenotypes from the Movement Disorder, Neurodegenerative Disorder, or Neuromuscular Disorder panels to create a custom panel.

Study of the panel genes from the DNA of a single individual allows us to focus on variants reported as pathogenic in the past, on those with a very low population frequency, with nucleotide conservation across species and with likely pathogenic consequence.  When variants of unknown significance are identified by panel testing, DNA is requested from first degree relatives to interrogate the significance of the variant.  There is no charge for added studies used to aid in interpretation of a sequence change found in the index case.

Reflex to Exome Sequencing:  If a causative or potentially causative variant is not identified by this exome panel test it is possible to order a REFLEX clinical exome.  The full exome sequence will be analyzed as is done for our Clinical Exome Sequencing test using the data obtained from the exome panel test.  Submission of parental samples, and or other family members may be needed to assist in the interpretation of sequence variants. Order REFLEX to EXOME SEQUENCING.

Neurodegenerative Disorder Panels

Posted on by Melanie Pepin

The Neurodegenerative Disorder Panels includes genes that have been identified to be responsible for disorders in which neurodegeneration is a noted feature including:
(select panel below for gene list)

For the above panels order testing on any or all of the phenotypes relevant to your patient.  If none of the panels fit your testing needs, select up to six phenotypes from the Movement Disorder, Neurodegenerative Disorder, or Neuromuscular Disorder panels to create a custom panel.

Study of the panel genes from the DNA of a single individual allows us to focus on variants reported as pathogenic in the past, on those with a very low population frequency, with nucleotide conservation across species and with likely pathogenic consequence.  When variants of unknown significance are identified by panel testing, DNA is requested from first degree relatives to interrogate the significance of the variant.  There is no charge for added studies used to aid in interpretation of a sequence change found in the index case.

Reflex to Exome Sequencing:  If a causative or potentially causative variant is not identified by this exome panel test it is possible to order a REFLEX clinical exome.   The full exome sequence will be analyzed as is done for our Clinical Exome Sequencing test using the data obtained from the exome panel test.  Submission of parental samples, and or other family members may be needed to assist in the interpretation of sequence variants. Order REFLEX to EXOME SEQUENCING.

 

Movement Disorder Panels

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The four NCGL Movement Disorder Panels include genes that have been identified to be responsible for Ataxia, Hereditary Spastic Paraplegia, Dystonia and Choreatic Movement Disorders, and Parkinson’s Disease (select name of panel for gene list):

Ataxia Panel Gene List
Hereditary Spastic Paraplegia Panel Gene List
Dystonia and Choreatic Move Disorders Panel Gene List
Parkinson’s Disease Panel Gene List

 

For the above panels order testing on any or all of the phenotypes relevant to your patient.  If none of the panels fit your testing needs, select up to six phenotypes from the Movement Disorder, Neurodegenerative Disorder, or Neuromuscular Disorder panels to create a custom panel.

Study of the panel genes from the DNA of a single individual allows us to focus on variants reported as pathogenic in the past, on those with a very low population frequency, with nucleotide conservation across species and with likely pathogenic consequence.  When variants of unknown significance are identified by panel testing, DNA is requested from first degree relatives to interrogate the significance of the variant.  There is no charge for added studies used to aid in interpretation of a sequence change found in the index case.

Reflex to Exome Sequencing:  If a causative or potentially causative variant is not identified by this exome panel test it is possible to order a REFLEX clinical exome.  The full exome sequence will be analyzed as is done for our Clinical Exome Sequencing test using the data obtained from the exome panel test.  Submission of parental samples, and or other family members may be needed to assist in the interpretation of sequence variants. Order REFLEX to EXOME SEQUENCING.

 

Recessive OI Panel + ALPL

Posted on by Melanie Pepin

PLEASE NOTE:  As of August 1, 2018 this panel has been replaced by the OI and Genetic Bone Disorders Panel.  Please contact the laboratory (206-543-5464) to special order.

Causative mutations have been identified in thirteen genes associated with autosomal recessive forms of Osteogenesis Imperfecta:  FKBP10, CRTAP, P3H1/LEPRE1, PPIB, SERPINH1, SP7/OSX, SERPINF1, PLOD2, ALPL, BMP1, TMEM38B, WNT1 and CREB3L1.  The CDL offers a testing panel that sequences these 13 genes simultaneously; this panel is recommended for those individuals with a clear clinical diagnosis of OI who have had normal COL1A1 and COL1A2 gene sequencing studies.  

When considering recessive forms of OI, consultation with the laboratory genetic counselors or laboratory director is recommended as clinical and family history and x-ray review may be needed.  Occasionally new candidate genes for recessive form of OI will be included as part of the panel; there is no additional charge for testing of these genes.

For guidelines on the correct test to order and for pertinent references, go to OI Guidelines for Diagnostic Testing.  

Comprehensive Dominant OI Panel

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PLEASE NOTE:  As of August 1, 2017 this panel has been replaced by the OI and Genetic Bone Disorders Panel.  Please contact the laboratory (206-543-5464) to special order.

The Comprehensive Dominant OI Panel offers sequencing for non-recessive forms of OI. Causative mutations have been identified in several genes associated with autosomal dominant forms of Osteogenesis Imperfecta (OI):  most commonly in COL1A1, COL1A2 and IFITM5 but also in P4HB, LRP5, ALPL and WNT1.  Recently, mutations in a single gene associated with X-linked OI, PLS3, have been identified.

Over 95% of OI phenotypes result from a single dominant mutation in either COL1A1 or COL1A2, the two genes that encode the chains of type I procollagen.  The phenotype that results from the disease-causing variant is a consequence of the underlying mutation type and location in the a1 or a2 chain of type I procollagen.  Null mutations of COL1A1 result in OI type I and missense mutations in either COL1A1 or COL1A2 result in variable phenotypes within a spectrum of age of onset, fracture frequency, stature and deformity.

OI type V is also a dominant form of OI resulting from a mutation in IFITM5, the gene that encodes interferon induced transmembrane protein 5.  Type V has a wide range of presentation but with distinguishing clinical and radiological features that can include a propensity to hyperplastic callus formation, calcification of the forearm interosseous membrane, radiodense metaphyseal bands, and radial head dislocation.

Hemizygous mutations in PLS3 are associated with osteoporosis and bone fragility in childhood.

For guidelines on the correct test to order and for pertinent references, consult the Osteogenesis Imperfecta Test Guide.

Autosomal Dominant OI Panel

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Causative mutations have been identified in three genes associated with autosomal dominant forms of Osteogenesis Imperfecta (OI):  COL1A1, COL1A2 and IFITM5.

 Over 95% of OI phenotypes result from a single dominant mutation in either COL1A1 or COL1A2, the two genes that encode the chains of type I procollagen.  The phenotype that results from the disease-causing variant is a consequence of the underlying mutation type and location in the a1 or a2 chain of type I procollagen.  Null mutations of COL1A1 result in OI type I and missense mutations in either COL1A1 or COL1A2 result in variable phenotypes within a spectrum of age of onset, fracture frequency, stature and deformity.

OI type V is also a dominant form of OI resulting from a mutation in IFITM5, the gene that encodes interferon induced transmembrane protein 5.  Type V has a wide range of presentation but with distinguishing clinical and radiological features that can include a propensity to hyperplastic callus formation, calcification of the forearm interosseous membrane, radiodense metaphyseal bands, and radial head dislocation.

For guidelines on the correct test to order and for pertinent references, consult the Osteogenesis Imperfecta Test Guide.

Classical and Vascular Ehlers-Danlos Syndrome Panel

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The Core Ehlers-Danlos gDNA sequencing Panel includes testing for the classic and the vascular forms of Ehlers-Danlos syndrome.   The classic type of Ehlers-Danlos syndrome (EDS types I & II) is an autosomal dominant disorder characterized by skin hyperextensibility, increased skin fragility, joint hypermobility, and abnormal wound healing. Recent studies indicate that as many as 90% of individuals with EDS classic type have underlying pathogenic variants in COL5A1 or COL5A2, the genes that encode type V collagen.  The vascular form of Ehlers-Danlos syndrome (vEDS) is characterized by thin, translucent skin with visible veins; marked bruising; joint dislocations; and the major complications of arterial, bowel and uterine rupture.

Please consult the Ehlers-Danlos Syndrome Test Guide for more information on the diagnosis.

Alport syndrome Panel

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The CDL offers a core testing panel sequencing 3 genes involved in Alport syndrome.  Pathogenic variants in the COL4A3, COL4A4, and COL4A5 genes, which code for type IV collagen, cause Alport syndrome. This panel is recommended for those individuals with possible autosomal recessive, autosomal dominant or X-linked Alport syndrome.  Genetic testing of COL4A5 as an individual gene is also offered for those families with clear X-linked inheritance pattern in their family.

Alport syndrome (AS) is a progressive glomerulonephritis characterized by kidney disease, hearing loss, and eye abnormalities. It has a prevalence of about 1 in 50,000 live births and may be inherited in an X-linked, autosomal dominant, or autosomal recessive manner. The majority of affected individuals have blood in their urine (hematuria), which indicates abnormal functioning of the kidneys, and also develop high levels of protein in their urine (proteinuria). The kidneys become less able to function as the disease progresses, resulting in end-stage renal disease. Progressive sensorineural hearing loss during childhood or adolescence and ocular symptoms (including maculopathy, posterior polymorphous dystrophy, and recurrent corneal erosion) are common. Anterior lenticonus is considered to be virtually pathognomonic for Alport syndrome.

COL5A1 and COL5A2 gDNA Testing

Posted on by Melanie Pepin

The classic type of Ehlers-Danlos syndrome (EDS types I & II) is an autosomal dominant disorder characterized by skin hyperextensibility, increased skin fragility, joint hypermobility, and abnormal wound healing. Recent studies indicate that as many as 90% of individuals with EDS classic type have underlying pathogenic variants in COL5A1 or COL5A2, the genes that encode type V collagen.

COL4A1 and COL4A2 gDNA Testing

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COL4A1 and COL4A2 encode the proα1(IV) and proα2(IV) chains, respectively, that form heterotrimers (2 proα1(IV) chains and a single proα2(IV) chain) in the type IV collagen that forms the vascular basement membranes outside the kidney and between tissues of different origins (e.g., epidermis and dermis in skin). Pathogenic variants in COL4A1 and COL4A2, have been associated with intracerebral hemorrhage in neonates and children, intracerebral hemorrhage and cerebral small vessel disease in adulthood, intracranial aneurysms, retinal arteriolar tortuosity, aneurysms and muscle cramp (HANAC) syndrome, infantile hemiparesis, and porencephaly.

COL3A1 gDNA testing

Posted on by Melanie Pepin

The vascular form of Ehlers-Danlos syndrome (vEDS) is characterized by thin, translucent skin with visible veins; marked bruising; joint dislocations; and the major complications of arterial, bowel and uterine rupture.

The vast majority of probands in families with this form of EDS are identified on the basis of a major complication either bowel perforation or vascular aneurysm or rupture. The International Ehlers-Danlos Foundation Advisory Board set the following guidelines for determination of the clinical diagnosis of EDS type IV. DNA-based testing is recommended for those who meet these guidelines. Note, however, that individuals with nonsense mutations of COL3A1 are less likely to have similar physical characteristics. The clinical diagnosis of EDS type IV is highly suspected when two major diagnostic criteria are present:

Major clinical diagnostic criteria:

  • Intestinal rupture
  • Arterial rupture
  • Uterine rupture during pregnancy
  • Family history of the vascular type of EDS

Minor diagnostic criteria alone are not sufficient to warrant the diagnosis unless identified in an individual with a major criteria.

  • Thin, translucent skin (especially noticeable on the chest/abdomen)
  • Easy bruising (spontaneous or with minimal trauma)
  • Characteristic facial appearance (thin lips and philtrum, small chin, thin nose, large eyes)
  • Acrogeria (an aged appearance to the extremities, particularly the hands)
  • Hypermobility of small joints
  • Tendon/muscle rupture
  • Early-onset varicose veins
  • Arteriovenous carotid-cavernous sinus fistula
  • Pneumothorax/pneumohemothorax
  • Chronic joint subluxations/dislocations
  • Congenital dislocation of the hips
  • Talipes equinovarus (clubfoot)
  • Gingival recession

Please consult the Ehlers-Danlos Syndrome Test Guide for more information on the diagnosis.

REFLEX to Exome Sequencing

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For the patient with a particular phenotype in whom focused “panel” sequencing did not identify a pathogenic variant in NCGL, further evaluation of the completed NCGL exome sequence data is offered.   Review of the patient’s exome sequence file may be the most cost effective way of expanding gene sequence testing beyond presently known disease candidate genes.  Study of the exome from the DNA of a single individual is used to identify sequence variants with a very low population frequency, with nucleotide conservation across species and likely pathogenic consequence. Testing of a family trio facilitates filtering of sequence variants and reduces the number of potential candidates by looking for the same sequence alteration in an unaffected parent(s).

Comprehensive Cardiac Arrhythmia/Cardiomyopathy Panel

Posted on by Melanie Pepin

The Comprehensive Cardiac Arrhythmia/Cardiomyopathy Panel includes genes that have been identified to be responsible for disorders in which arrhythmia and/or cardiomyopathy are a noted feature:

Comprehensive Cardiac Arrhythmia and Cardiomyopathy Panel Gene List

Cardiac Arrhythmia disease phenotypes include Brugada syndrome, Familial atrial fibrillation, long QT, and arrhythmogenic right ventricular dysplasia among others.  Cardiomyopathy disease phenotypes include primary myopathies, muscular dystrophies; metabolic storage diseases, Noonan syndrome and cardiofaciocutaneous syndromes among others.  The Comprehensive Cardiac Arrhythmia/Cardiomyopathy exome panel is the most cost-efficient and precise approach to diagnostic testing as there is overlap between phenotypes and the lack of characteristic “other” features in many instances. Study of the panel genes from the DNA of a single individual allows us to focus on variants reported as pathogenic in the past, on those with a very low population frequency, with nucleotide conservation across species and with likely pathogenic consequence. When variants of unknown significance are identified by panel testing, DNA is requested from first degree relatives to interrogate the significance of the variant. There is no charge for added studies used to aid in interpretation of a sequence change found in the index case.

Reflex to Exome Sequencing:  If a causative or potentially causative variant is not identified by this exome panel test it is possible to order a REFLEX clinical exome.   The full exome sequence will be analyzed as is done for our Clinical Exome Sequencing test using the data obtained from the exome panel test.  Submission of parental samples, and or other family members may be needed to assist in the interpretation of sequence variants. Order REFLEX to EXOME SEQUENCING.

Cardiomyopathy Panel

Posted on by Melanie Pepin

Cardiomyopathy exome panel testing includes over 70 genes that have been identified to be responsible for disorders in which cardiomyopathy is a noted feature:

Cardiomyopathy Panel Gene List

The disease phenotypes include primary myopathies, muscular dystrophies; metabolic storage diseases, Noonan syndrome and cardiofaciocutaneous syndromes among others.   Cardiomyopathy exome panel testing is the most cost-efficient and precise approach to diagnostic testing as there is overlap between phenotypes and the lack of characteristic “other” features in many instances.   Study of the panel genes from the DNA of a single individual allows us to focus on variants reported as pathogenic in the past, on those with a very low population frequency, with nucleotide conservation across species and with likely pathogenic consequence. When variants of unknown significance are identified by panel testing, DNA is requested from first degree relatives to interrogate the significance of the variant. There is no charge for added studies used to aid in interpretation of a sequence change found in the index case.

Reflex to Exome Sequencing:  If a causative or potentially causative variant is not identified by this exome panel test it is possible to order a REFLEX clinical exome.   The full exome sequence will be analyzed as is done for our Clinical Exome Sequencing test using the data obtained from the exome panel test.  Submission of parental samples, and or other family members may be needed to assist in the interpretation of sequence variants. Order REFLEX to EXOME SEQUENCING.

Cardiac Arrhythmia Panel

Posted on by Melanie Pepin

Cardiac Arrhythmia exome panel testing includes more than 50 genes that have been identified to be responsible for disorders in which arrhythmia is a noted feature:

Cardiac Arrhythmia Panel Gene List

The disease phenotypes include Brugada syndrome, Familial atrial fibrillation, long QT, and arrhythmogenic right ventricular dysplasia among others.   Cardiac Arrhythmia exome panel testing is the most cost-efficient and precise approach to diagnostic testing as there is overlap between phenotypes and the lack of characteristic “other” features in many instances.   Study of the panel genes from the DNA of a single individual allows us to focus on variants reported as pathogenic in the past, on those with a very low population frequency, with nucleotide conservation across species and with likely pathogenic consequence. When variants of unknown significance are identified by panel testing, DNA is requested from first degree relatives to interrogate the significance of the variant. There is no charge for added studies used to aid in interpretation of a sequence change found in the index case.

Reflex to Exome Sequencing:  If a causative or potentially causative variant is not identified by this exome panel test it is possible to order a REFLEX clinical exome.   The full exome sequence will be analyzed as is done for our Clinical Exome Sequencing test using the data obtained from the exome panel test.  Submission of parental samples, and or other family members may be needed to assist in the interpretation of sequence variants. Order REFLEX to EXOME SEQUENCING.

FBN1 gDNA Testing

Posted on by Melanie Pepin

Mutations in FBN1 can result in several phenotypes, the most frequent of which is Marfan syndrome that is characterized by relative tall stature, arachnodactyly, kyphoscoliosis, chest deformity, lens dislocation and a high risk for aortic aneurysm and dissection. In addition to Marfan syndrome mutations in FBN1 can cause dominantly inherited forms of geleophysic dysplasia, acromicric dysplasia, Weill Marchesani syndrome, and stiff skin syndrome.

Please consult our Familial Aneurysm Test Guide to learn more about when to test for mutations in FBN1.

Marfan Syndrome and Loeys-Dietz Panel

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The CDL offers a core testing panel sequencing 8 genes involved in familial aneurysmal disorders, particularly Marfan syndrome and Loeys-Dietz syndrome: FBN1, TGFBR1, TGFBR2, TGFB2, TGFB3, SMAD2, SMAD3, and SMAD4.  This panel is recommended for those individuals with clinical characteristics of Marfan or Loeys-Dietz syndrome including arterial aneurysms, dissection, rupture) and a family history of similar complications. 

COL1A1 and COL1A2 gDNA Testing

Posted on by Melanie Pepin

Over 95% of the forms of OI (lethal and non-lethal) result from a single dominant mutation in either COL1A1 or COL1A2, the two genes that encode the chains of type I procollagen.  The phenotype that results from the disease-causing variant is a consequence of the underlying mutation type and location in the alpha 1 or alpha 2 chain of type I procollagen.  Null mutations of COL1A1 result in OI type I and missense mutations in either COL1A1 or COL1A2 result in variable phenotypes within a spectrum of age of onset, stature and deformity.

For guidelines on the correct test to order and for pertinent references, consult the Osteogenesis Imperfecta Test Guide.

Arterial Aneurysm Panel

Posted on by Melanie Pepin

The CDL offers a testing panel sequencing 25 genes associated with familial arterial aneurysms, including genes for Marfan Syndrome, Loeys-Dietz syndrome, vascular Ehlers-Danlos Syndrome, and TAAD: ACTA2, COL3A1, FBN1, FBN2, MAT2A, MYH11, MYLK, PRKG1, SKI, SLC2A10, SMAD3, TGFBR1, TGFBR2, TGFB2, TGFB3, FOXE3, BGN, LOX, MFAP5, NOTCH1, PLOD3, SMAD2, SMAD4, SMAD6, COL1A1, and CBS.  This panel is recommended for those individuals with vascular complications (arterial aneurysms, dissection, rupture) and a family history of similar complications with features overlapping with Marfan Syndrome and vascular Ehlers-Danlos Syndrome.  Please consult our Test Guide on Familial Aneurysm for more information.

Flow Cytometry – Paraffin Specimens

Posted on by Melanie Pepin

The Clinical Flow Cytometry laboratory performs DNA content and cell cycle analyses of solid tissue specimens. The laboratory’s special expertise is in DNA content measurements of premalignant diseases of the GI tract, such as Barrett’s esophagus and ulcerative colitis, where the finding of DNA content abnormalities is associated with elevated cancer risk, and the determination of ploidy in the differential diagnosis of molar pregnancies.

Flow Cytometry – Fresh Specimens

Posted on by Melanie Pepin

The Clinical Flow Cytometry laboratory performs DNA content and cell cycle analyses of solid tissue specimens. The laboratory’s special expertise is in DNA content measurements of premalignant diseases of the GI tract, such as Barrett’s esophagus and ulcerative colitis, where the finding of DNA content abnormalities is associated with elevated cancer risk, and the determination of ploidy in the differential diagnosis of molar pregnancies.

 

Flow Cytometry – Endoscopic Biopsy

Posted on by Melanie Pepin

The Clinical Flow Cytometry laboratory performs DNA content and cell cycle analyses of solid tissue specimens. The laboratory’s special expertise is in DNA content measurements of premalignant diseases of the GI tract, such as Barrett’s esophagus and ulcerative colitis, where the finding of DNA content abnormalities is associated with elevated cancer risk, and the determination of ploidy in the differential diagnosis of molar pregnancies.

COL4A5 gDNA testing

Posted on by Melanie Pepin

Genetic testing of COL4A5 as an individual gene is offered for those families with clear X-linked inheritance of Alport Syndrome.

Alport syndrome (AS) is a progressive glomerulonephritis characterized by kidney disease, hearing loss, and eye abnormalities. It has a prevalence of about 1 in 50,000 live births and may be inherited in an X-linked, autosomal dominant, or autosomal recessive manner. The majority of affected individuals have blood in their urine (hematuria), which indicates abnormal functioning of the kidneys, and also develop high levels of protein in their urine (proteinuria). The kidneys become less able to function as the disease progresses, resulting in end-stage renal disease. Progressive sensorineural hearing loss during childhood or adolescence and ocular symptoms (including maculopathy, posterior polymorphous dystrophy, and recurrent corneal erosion) are common. Anterior lenticonus is considered to be virtually pathognomonic for Alport syndrome.

Testing for Known Pathogenic Variant

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The Northwest Clinical Genomics Laboratory (NCGL) offers targeted analysis for variants previously identified in our laboratory.  Known pathogenic variant testing should be selected if such a variant was previously identified in the family by the NCGL (we tested a relative of the patient) and we have a positive control for that patient.