Whole Exome Sequencing

Whole Exome Sequencing:

Introduction

Whole-exome sequencing (WES) is a diagnostic approach for the identification of molecular defects in patients with suspected genetic disorders. Exome Sequencing is a test that looks at approx.20,000 genes. This test may be useful for patients whose medical and family histories suggest a genetic cause for their signs and symptoms. Most patients who have whole exome sequencing have had other genetic testing that did not find a genetic cause of their condition. Research has shown that exome sequencing could detect genetic mutations related to birth defects and developmental delays. So patients who have a family history of disease or are searching for a diagnosis to explain symptoms may be able to avoid unnecessary diagnostic tests by undergoing exome sequencing. Exome Sequencing is a test for identifying disease-causing DNA variants within the 1% of the genome which codes for proteins (exons) or flanks the regions which code for proteins (splice junctions).

Testing Indication

Exome sequencing can be used to diagnose the genetic cause of disease like:

• Identification of the underlying disease gene mutation(s) that can have major implications for diagnostic and therapeutic approaches,
• A complex, unspecific genetic disorder with multiple differential diagnoses and makes it possible to test at-risk family members.
• A genetically heterogeneous disorder
• A suspected genetic disorder where a specific genetic test is not available
• Unsuccessful previous genetic testing

Testing Benefit

• This method allows variations in the protein-coding region of any gene to be identified, rather than in only a select few genes.
• Because most known mutations that cause disease occur in exons, whole exome sequencing is thought to be an efficient method to identify possible disease-causing mutations.
• Whole exome sequencing is a state-of-the-art molecular diagnostic genetic test. It has the potential to rapidly and efficiently detect disease-causing genetic mutations within any gene in the human genome and is therefore becoming widely used in clinical practice.

Sample Required for testing:

Whole Blood - 4-5ml in EDTA (purple capped tube)

Whole Exome Sequencing Trio:

Introduction

Trio studies, which involve the testing of samples from a proband and both parents, are often used to help with the classification of genetic variants, including copy number variants. The Trio Whole Exome Sequencing test is a highly complex test that is newly developed for the identification of changes in a patient's DNA that are causative or related to their medical concerns. Trio study which includes father, mother, and child can identify inherited or non-inherited and de novo mutations in a child and aids in classification of putative causal variants, so distinguish false positive variants from true pathogenic variants.

Testing Indication

• Identification of the underlying disease gene mutation(s) that can have major implications for diagnostic and therapeutic approaches,
• A complex, unspecific genetic disorder with multiple differential diagnoses and makes it possible to test at-risk family members.
• A genetically heterogeneous disorder
• A suspected genetic disorder where a specific genetic test is not available
• Unsuccessful previous genetic testing

Testing Benefit

• Trio Exome Analysis using whole exome/ clinical exome sequencing facilitates analyses of thousands of genes simultaneously to identify genetic alterations like insertions/ deletions (indels), single nucleotide variants (SNVs) and copy number variations (CNVs).
• This familial analysis-based approach benefits in excluding variants, which do not conform to Mendelian transmission, so reducing false positive calls and variants.
• Gives better diagnostic yield compared to analyzing single proband sample, analysis of inheritance like autosomal recessive, autosomal dominant and clinically relevant variants for compound heterozygous and de novo variants.
• Our rigorous variant classification scheme

Sample Required for testing:

Whole Blood - 4-5ml in EDTA (purple capped tube)

Inborn Errors of Metabolism:

Introduction

Inborn errors of metabolism are rare genetic (inherited) disorders. The disorders are usually caused by defects in specific proteins (enzymes) that help break down (metabolize) parts of food. Inherited metabolic diseases, also called inborn errors of metabolism, are heritable (genetic) disorders. Most people with inherited metabolic disorders have a defective gene that results in an enzyme deficiency. Some symptoms of inherited metabolic disorders include lethargy, abdominal pain, weight loss, developmental delays, seizures, coma etc. Some examples of Inborn errors of metabolism presenting in adolescents and adults are, Gaucher disease type 1, X-linked adrenoleukodystrophy, Wilson disease, 3-methylcrotonyl CoA carboxylase deficiency.

Testing Indication

• Metabolic disorders, blood diseases, genetic disorders
• Dermatologic-Brittle hair, dry scaly skin
• Ophthalmologic-Corneal clouding, cataracts, keratitis
• Cardiac or hepatic- cardiac failure, organomegaly, liver damage
• Musculoskeletal- Muscle weakness, poor muscle mass
• Neurologic- seizures, Neonatal hypo or hypertonia

Testing Benefit

• Earlier recognition of inborn errors of metabolism has the potential to reduce morbidity and mortality rates in affected infants.
• Earlier identification of inborn errors of metabolism in asymptomatic can detect treatable metabolic disorders in any person.
• Our rigorous variant classification scheme.

Sample Required for testing:

Whole Blood - 4-5ml in EDTA (purple capped tube)

Noonan syndrome:

Introduction

Noonan syndrome is a genetic disorder that prevents normal development in various parts of the body. These include unusual facial characteristics, short stature, heart defects, other physical problems and possible developmental delays. Other names are Male Turner syndrome, Noonan–Ehmke syndrome, Turner-like syndrome, Ullrich–Noonan syndrome. Noonan syndrome is caused by a faulty gene, which is usually inherited from one of the child's parents. Noonan syndrome (NS) is a common genetic syndrome associated with gain of function variants in genes in the Ras/MAPK pathway. There's no evidence to suggest the genetic fault is caused by environmental factors, such as diet or exposure to radiation.

Testing Indication

• Noonan syndrome is usually made after a doctor observes some key signs.
• Abnormalities of the eyes and eyelids.
• Short Stature
• Cardiovascular Abnormalities

Testing Benefit

• Clarify diagnosis and risk of congenital heart disease.
• Target medical management and prevention of cardiac arrest and other complications.
• Our rigorous variant classification scheme.

Sample Required for testing:

Whole Blood - 4-5ml in EDTA (purple capped tube)