2013 ACMG Ambry Genetics Exome Posters

• Family-based exome sequencing reveals that de novo alterations make up a significant portion of previously undiagnosed patients
• Apparent digenic trialleleic inheritance in early-­onset ataxia through whole exome sequencing
• Diagnostic Exome Sequencing Suggests Digenic Inheritance in a Cobalamin Metabolism Disorder
• Exome sequencing in a patient with syndromic intellectual disability identifies ZNF238, a novel gene which lies within the 1q43q44 microdeletion syndrome
• Nonsense mutations identified in UBE3B in a patient with Blepharophimosis-­Ptosis-­Intellectual Disability Syndrome by clinical diagnostic exome
• Clinical exome sequencing identifies a novel gene, SNAP25, associated with seizures
• Clinical Diagnostic Exome Sequencing Identified a novel Mutation in ACTG2, Possibly Due to Germline Mosaicism, in Two Affected Children with Megacystis and Echogenic Bowel in a Chinese Family

First-Tier Exome™ and  Clinical Diagnostic Exome™
Ambry Genetics offers a flexible, tiered approach to exome sequencing in order to accommodate the variable needs of clinicians and to assist in the diagnosis and medical management of patients.

For all scenarios we ask that you send samples from the entire family from the beginning of testing for co-segregation analysis.  

Exome sequencing test options:
1.  First-Tier Exome (analysis of ~4,000 characterized genes)
2.  First-Tier Exome reflex to Clinical Diagnostic Exome
3.  Clinical Diagnostic Exome (testing of trios; analysis of ~20,000 RefSeq genes)

First-Tier Exome:
The role of genes in human disease has only been defined in approximately 20% (~4,000 of ~20,000 genes) of the human exome.  The First-Tier Exome analyzes the DNA sequence of the exons (coding regions) and flanking intronic regions of these ~4,000 genes.  The targeted exome sequencing provided by the First-Tier Exome is appropriate for a variety of exome sequencing indications and will yield the answers clinicians are seeking in many clinical scenarios without the added expense and complexity of whole exome analysis.

First-Tier Exome reflex to Clinical Diagnostic Exome:
This test offers clinicians the option to begin with the First-Tier Exome, but if First-Tier does not render a genetic diagnosis, Ambry will reflex to the Clinical Diagnostic Exome to try to solve the diagnostic odyssey for this patient and his/her family.

Clinical Diagnostic Exome (CDE):
This is the most comprehensive option clinically available on the market. This test includes analysis and interpretation of coding regions (exons) of virtually all genes in the human genome (~20,000 RefSeq genes). This option includes whole exome sequencing for family trios and analysis and reporting of novel gene discoveries. Co-segregation analysis is also included. Send samples from the entire family from the beginning of testing and Ambry will select the three individuals to construct the trio to provide the most informative results.
Please note: This test is not available for fetal demise samples.

For testing forms and requirements, please visit Ambry's Exome Requirements.

Consent forms for receipt of raw data (for research purposes):

• CDE Candidate Alterations Request Consent Form

Indications for Testing

• A patient’s clinical condition has become a “diagnostic odyssey.”  A family may have already pursued all testing available thus far in search for a diagnosis for their child’s medical condition(s).  Exome sequencing may be the ideal next step on this search for clarity and understanding.
• A genetic disorder is suspected based on clinical findings, but limited and/or no comprehensive panels are available.
• The patient's clinical presentation is unclear/atypical disease and there are multiple genetic conditions in the differential diagnosis.
• A novel gene is suspected, but has yet to be discovered.  In this case, Clinical Diagnostic Exome would be most appropriate.