When the mitochondria do not function properly in human body, a number of diseases appear, which are labeled as metabolic disorders. If the mitochondria are not working properly, a waste product such as lactic acid can build up in the bloodstream. This helps distinguish mitochondrial diseases from other metabolic diseases. Our laboratory recommends sequencing the entire mitochondrial genome and/or performing a comprehensive nuclear gene panel to confirm the diagnosis and identify a specific mitochondrial syndrome.

Our test is based on a highly sensitive digital PCR technology to detect deletions and duplications of mitochondrial DNA. It is the only method available that allows absolute assessment of heteroplasmy. The risk of false negatives and false positives is greatly reduced.

Test benefits:

• Differentiation of a specific subtype of mitochondrial disease.
• Identification of mitochondrial genome gene variants associated with mitochondrial diseases. This allows testing of at-risk family members.
• Use of whole mitochondrial genome amplification by long-range PCR (LR-PCR) followed by next-generation sequencing to evaluate variants in the mitochondrial genome.
• Confirmation of pathologies arising from variants in nuclear-encoded genes or the mitochondrial genome.
• Molecular diagnosis of congenital lactoacidosis.
• Use of NGS to identify single nucleotide variants and copy number variants in 28 genes associated with congenital lactoacidosis.

Tests:

• MITOP | Mitochondrial whole-genome analysis, next-generation sequencing, varied
• NMITO | Nuclear mitochondrial gene panel, next generation sequencing, varies
• CMITO | Combined Mitochondrial and Nuclear Whole Genome Panel, varies
• CLADP | Congenital Lactoacidosis Panel, varies

Growth differentiation factor-15

It is a cytokine that belongs to the transforming growth factor family, its activity is significantly increased during stress and inflammation. Also mitochondrial diseases Also, patients with mitochondrial diseases may have low growth factor-15 in plasma or serum.

Tests:

• GDF15 | Growth differentiation factor-15, plasma
• OAU | Organic Acid Screening, random, urine
• AAQP | Amino Acids, quantitative, plasma
• Q10 | Coenzyme Q10, total, plasma
• FAPM | Fatty Acid Profile, mitochondria (C8-C18), serum
• PYR | Pyruvic acid, blood
• PYRC Pyruvate, cerebrospinal fluid

A mutation in a gene can put a person at risk of developing epilepsy. These are often genes that control the excitability of nerve cells in the brain. However, many people with genetic mutations may never develop the disease. Our laboratory offers a molecular genetic diagnostic panel, which is based on an in-depth mutation and variant (CNV) analysis using next-generation sequencing. This allows us to determine the causes of the disease and select the best treatment options.

Test benefits:

• Detecting the presence of a mutation in genes associated with inherited epilepsy or seizure disorder, allowing predictive screening of at-risk family members.
• Use of next-generation sequencing to detect single nucleotides and copy number variants in 319 genes, and PCR-based analysis to detect extensions of CSTB dodecameric repeats.
• Impact on patient treatment and management by identifying the specific cause of disease.
• Molecular confirmation of progressive myoclonic epilepsy associated with CSTB.
• Molecular diagnosis of patients with hemiplegic migraine by detection of single nucleotides and copy number variants in 9 genes.
• Identification of pathogenic variants in the MECP2 gene associated with Rett syndrome and MECP2-related disorders.
• Diagnosis of individuals with features of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy and NOTCH3-related disorders.
• Identification of pathogenic variants in the TSC1 and TSC2 genes associated with tuberous sclerosis allows testing of at-risk family members.
• Prenatal diagnosis in fetuses with ultrasonographic signs of tuberous sclerosis (e.g., cardiac rhabdomyomas).

Tests:

• EPPAN | Comprehensive Epilepsy Gene Panel with or without encephalopathy, varies
• CSTB | CSTB gene, repeat expansion analysis, varies
• HMEP | Hemiplegic migraine with or without epilepsy, gene panel, varies
• MCP2Z | MECP2 gene, complete gene analysis, varies
• NTC3Z | NOTCH3 gene, complete gene analysis, varies
• TSCP | Tuberous sclerosis gene panel, varies

A group of diseases that are categorized as motor and sensory; sensory and autonomic; motor. Hereditary neuropathies may be primary or secondary to other diseases including Refsum’s disease, porphyrin disease, and Fabry disease. The use of next-generation sequencing (NGS) can help determine the genetic nature of neuropathy. Conducting the tests allows for the selection of gene-specific therapies. 

A comprehensive panel of hereditary neuropathy

The use of next-generation sequencing to evaluate 187 genes associated with hereditary neuropathy greatly simplifies the diagnostic process. The panel, developed by geneticists and neurologists, includes only clinically relevant tests.

Test benefits:

• Molecular diagnosis of patients with peripheral neuropathy.
• Identification of gene variants associated with peripheral neuropathy, allowing testing of at-risk family members.
• Utilizing next-generation sequencing to detect single nucleotides and copy number variants in 187 genes.
• Identification of the cause of the disease can aid in diagnosis, prognosis, clinical management of the patient, risk assessment for relapse, and genetic counseling.

Tests:

• PEPAN | Comprehensive Peripheral Neuropathy Gene Panel, varied

Amyotrophic lateral sclerosis and frontal temporal dementia

Amyotrophic lateral sclerosis is a disease in which motor neurons of the brain and spinal cord are affected. It is characterized by the development of disorders of motor functions, the ability to breathe, swallow, speak. It is often combined with frontal temporal dementia, a condition in which there is degradation of cortical neurons and the development of personality changes. Genetic testing to evaluate neurodegenerative conditions is becoming an increasingly important component of patient diagnosis and treatment.

Test benefits:

• Molecular confirmation of suspected cases of c9FTD/ALS, frontal temporal dementia or amyotrophic lateral sclerosis.
• Presymptomatic testing for individuals with a family history of c9FTD/ALS and a documented expansion of the C9orf72 gene.
• Use of next-generation sequencing to detect single nucleotides and copy number variants in 51 genes that are associated with frontal temporal dementia and/or amyotrophic lateral sclerosis.
• Detection of variants in the SOD1 gene, allowing screening of at-risk family members.

Tests:

• C90RF | C9orf72 hexanucleotide repeat, molecular analysis, varies 
• AFTDP | Hereditary frontal temporal dementia and amyotrophic lateral sclerosis gene panel, varies 
• SOD1Z | SOD1 gene, complete gene analysis, varies

Parkinson’s disease

A slowly progressive chronic neurodegenerative neurological disease. Predominantly occurs in older adults. It is caused by progressive destruction and death of neurons that produce dopamine. Lack of the latter causes an inhibitory effect of the basal ganglia on the cerebral cortex. The onset and progression of Parkinson’s disease symptoms can be delayed by understanding a patient’s genetic predisposition.

Genetic testing is also important for patients who have the disease at an earlier age, which is more likely to be triggered by genetic causes. Although genetic variation is only present in 10-15% of patients, knowledge of specific genetic factors can enhance understanding of progression and treatment.

Test benefits:

• Utilizing next-generation sequencing to detect single nucleotides and copy number variants in 94 genes associated with Parkinson’s disease.
• Establishing a molecular diagnosis.
• Identification of increased risk and the ability to delay the onset and progression of symptoms.

Tests:

• PARDP | Hereditary Parkinson’s disease gene panel, varies

Personalized Gene Sequencing

Our lab’s customizable next-generation sequencing panels are designed to meet the needs of each patient. Once a disease is selected and a gene panel is customized, a custom identifier is created, which is a specific code that directs lab technicians to the genes to be studied.

Tests:

• CGPH | Customized Gene Panel, Hereditary, Next-Generation Sequencing, Varies

Hereditary movement disorders

Ataxia (loss of coordination between muscles without muscle weakness) causes difficulty walking, balance, hand coordination, speech, and swallowing. It is often caused by cerebellar damage, cancer, alcohol abuse, stroke, multiple sclerosis, and certain medications, but may also have genetic causes. Hereditary ataxias can be autosomal dominant or autosomal recessive, with different genetic variants causing different types, most of which progress rapidly.

Test benefits:

• Uses next-generation sequencing to detect single nucleotides and copy number variants in 198 genes associated with ataxia.
• ​Monitors frataxin levels in patients with Friedreich’s ataxia. Decreased frataxin protein levels are a valuable diagnostic feature and can be used for ongoing medical monitoring.
• Assess CAG repeat expansions in the ATXN1, ATXN2, ATXN3, CACNA1A, and ATXN7 genes associated with spinocerebellar ataxia types 1, 2, 3, 6, and 7.
• Assess one type of specified spinocerebellar ataxias, including types 1, 2, 3, 6, or 7. For prenatal samples only.
• Molecular diagnosis of patients with hereditary spastic paraplegia by detecting single nucleotides and copy number variants in 128 genes.
• Molecular confirmation of clinically suspected cases of Huntington’s disease. Presymptomatic testing for individuals with a family history and a documented HTT gene expansion.

Tests:

• ATAXP | Hereditary Ataxia Gene Panel, varies
• FFRWB | Friedreich’s Ataxia, Frataxin, Quantitative, Blood
• SCAP | Spinocerebellar Ataxia Repeat Expansion Panel, varies
• SCARA | Spinocerebellar Ataxia Type 1, 2, 3, 6, or 7, Repeat Expansion Assay, varies
• ISPP | Hereditary Spastic Paraplegia Gene Panel, varies • HAD | Huntington’s Disease, Molecular Assay, varies

Neuralgic Amyotrophy

Identification of variants in the SEPTIN9 gene associated with hereditary neuralgic amyotrophy allows testing of at-risk family members using next-generation sequencing.

Tests:

SEP9Z | SEPTIN9 gene, full gene analysis, variable

Distal myopathy and peripheral neuropathy

The diagnostic panel evaluates 211 genes associated with distal frailty, as well as deletions and duplications of SMN1 and SMN2.

Tests:

• DWPAN | Comprehensive distal frailty gene panel, variable 

Additional tests

Test benefits:

• Evaluates large deletions and duplications of the PMP22 gene to diagnose Charcot-Marie-Tooth syndrome type 1A or hereditary neuropathy with liability to pressure palsies.
• Analysis of 87 genes associated with hereditary motor and sensory neuropathies.
• Evaluation of 24 genes associated with hereditary motor neuropathies, as well as deletion and duplication analysis of SMN1 and SMN2.
• Analysis of 128 genes associated with hereditary spastic paraplegia and 23 genes associated with hereditary sensory neuropathies.
• Molecular diagnostics of patients with amyloidosis.
• Next-generation sequencing to detect single nucleotide and copy number variants in one gene associated with amyloidosis: TTR. 

Tests:

• PMPDD | PMP22 gene, large deletion/duplication analysis, variable
• IMSNP | Hereditary motor and sensory neuropathy gene panel, variable
• IMNP | Hereditary motor neuropathy gene panel, variable
• ISPP | Hereditary spastic paraplegia gene panel, variable
• ISNP | Hereditary Sensory Neuropathy Gene Panel, Varies
• TTRZ | TTR Gene, Complete Gene Analysis, Varies

This is a conditional group of diseases characterized by impaired muscle function, primarily their weakness. Neuromuscular disorders include diseases of the muscles, peripheral nerves, neuromuscular junction and motor neuron. The set of genetic tests for hereditary neuromuscular disorders includes comprehensive and targeted panels of the new generation. Our panels, developed by a team of physicians, geneticists and laboratory experts, include only clinically significant genes recommended in numerous professional guidelines. The use of NGS allows for complete coverage of all included genes and provides high sensitivity for the detection of variants with both low and high copy numbers. 

Test benefits:

• Obtaining a rapid expert opinion on muscle biopsy samples to diagnose acquired or hereditary diseases.
• Evaluation of nerve diseases and disorders affecting nerve function.
• Study of polyneuropathies.
• Detect single nucleotides and copy number variants in a custom gene panel.
• Use next-generation sequencing to detect single nucleotides and copy number variants in 215 genes associated with neuromuscular disorders.

Tests:

• MBX | Muscle Consultation
• PNBX | Peripheral Nerve Consultation
• SPBX | Epidermal Nerve Fiber Density Consultation, Varies
• CGPH | Custom Gene Panel, Hereditary, Next-Generation Sequencing, Varies
• MUPAN | Comprehensive Neuromuscular Gene Panel, Varies

Muscular Dystrophy

Genetic testing not only helps patients with muscular dystrophy get the right diagnosis and treatment, but also helps families plan for the future. The panel can also help patients and health care providers access disease-specific treatments and assess patient eligibility for clinical trials. 

Test Benefits:

• Assesses 75 genes associated with muscular dystrophy.
• Assesses 65 genes associated with limb-girdle muscular dystrophy and congenital myasthenic syndrome.
• Assesses 7 genes associated with Emery-Dreifuss muscular dystrophy.
• Confirms a diagnosis of Duchenne muscular dystrophy or Becker muscular dystrophy.
• Detects mutations and copy number variations in the DMD gene to diagnose Duchenne muscular dystrophy.

Tests:

• MDYSP | Hereditary Muscular Dystrophy Gene Panel, Variable
• LGCMP | Hereditary Limb-Girdle Muscular Dystrophy and Congenital Myasthenic Syndrome Gene Panel, Varies
• EDMDP | Emery-Dreifuss Inherited Gene Panel, Varies
• DBMD | Duchenne/Becker Muscular Dystrophy, DMD Gene, Large Deletion/Duplication Analysis, Varies
• DMDZ | DMD Gene, Complete Genetic Analysis, Varies

Musculoskeletal Channelopathies

Using next-generation sequencing to detect single nucleotide and copy number variants in 5 genes associated with skeletal muscular channelopathies: ATP1A2, CACNA1S, CLCN1, KCNJ2, SCN4A.

Tests:

• SMCP | Hereditary Skeletal Muscle Channelopathy Gene Panel, Varies

Motor Neuron Diseases

A group of rare neurodegenerative diseases that selectively affect motor neurons, the cells that control striated muscle in the body.

Test Benefits:

Assess 33 motor neuron disease-associated genes and analyze the C9orf72 repeat expansion.

Identify single nucleotide and copy number variants in the SOD1 gene, allowing testing of at-risk family members.

Confirm clinically suspected cases of c9FTD/ALS, FTD, or ALS. 

Identify and evaluate survival motor neuron 1 exon 7 (SMN1), SMN2 exon 7, and rs143838139 SMN1 (g.27134T>G) associated with SMA.

Tests:

• MNDP | Hereditary Motor Neuron Disease Gene Panel, Varies
• SOD1Z | SOD1 gene, complete gene analysis, variable
• C9ORF | C9orf72 hexanucleotide repeat, molecular analysis, variable
• SMNDX | Spinal muscular atrophy diagnostic test, deletion/duplication analysis, variable
• SBULB | Spinobulbar muscular atrophy (Kennedy disease), molecular analysis, variable

Myopathy

The test detects individual nucleotides and copy number variations in 83 genes associated with rhabdomyolysis and metabolic myopathy. 

Tests:

• RABMP | Hereditary Rhabdomyolysis and Metabolic Myopathy Panel, Varies

Neuromuscular Junction Disorders

Analysis of 28 genes associated with congenital myasthenic syndromes.

Tests:

• CMSP | Congenital Myasthenic Syndrome Gene Panel, Varies