GeneDx can provide Mutation-Specific Testing for known familial mutations, in any gene, for families that have had previous testing at GeneDx or elsewhere. Mutation-Specific Testing always requires that sufficient information is provided (see tabs below for details). Mutation-Specific Testing is offered for both symptomatic and asymptomatic individuals, and for dominant or recessive mutations. Mutation-Specific Testing is less costly and more rapid than diagnostic analysis of the whole gene.
Reasons for Performing Mutation-Specific Testing:
- Targeted mutation testing in the parents of a child with a specific dominant mutation, in order to determine if the mutation was inherited or newly acquired (de novo).
- Carrier testing for the parents of a child apparently homozygous for a recessive mutation, to rule out the possibility that the child has one mutated allele and one allele that is deleted or refractory to amplification.
- Carrier testing for the parents of a child who has two mutations associated with a recessive disorder to confirm that the mutations are present on two different alleles and that all four parental alleles can be detected prior to prenatal diagnosis.
- Pre-symptomatic testing in siblings of the index case.
- Mutation-specific testing in the extended family.
- Clinical laboratory confirmation of one or more mutations identified in a research lab.
STEPS when family member was previously tested at GeneDx
1. Mutation-Specific Testing in both parents of proband prior to testing other family members is recommended.
2. Following information is required on Cardiology Test Requisition Form
- Name of the gene
- Name of the mutation
- GeneDx accession number or the full name of the positive relative that we previously tested.
3. Submit specimen. Our standard specimens for all tests are one pair of GeneDx buccal brushes or a single tube with 2-5 mL blood in EDTA. DNA specimens are also accepted. TAT will be 4-5 weeks in most cases.
– Family member previously tested at GeneDx
Using genomic DNA, the regions of interest are examined by bi-directional sequence analysis and/or by other methods, such as heteroduplex analysis or restriction enzyme digestion. The previously tested proband’s DNA serves as the positive control.
STEPS when family member was tested at an Outside Laboratory
1. Submission of the outside molecular lab results to GeneDx is required. To clearly identify the mutation, lab results must include:
- The name of the gene
- The mutation in cDNA-level notation (e.g. residue c.123 G to T, where c.1 is the A of the ATG)
- One of the following:
- The mutation given at the protein level notation (e.g. Gly12Ser or G12S)
- The mutation given in g-DNA level notation, with reference to a specific public reference sequence
- A DNA sequence at least 30 bases long with the mutated base and mutation indicated
2. If the individual to be tested is NOT the proband who was previously tested at the outside laboratory, it is strongly recommended to provide DNA from the proband as a positive control
3. Mutation-Specific Testing in both parents of proband prior to testing other family members is recommended
5. Submit specimen. Our standard specimens for all sequencing tests are one pair of GeneDx buccal brushes or a single tube with 2-5 mL blood in EDTA. DNA specimens are also accepted. TAT will be 4-5 weeks in most cases, unless pos control needs to be tested.
– Family member previously tested at an Outside Laboratory
GeneDx performs the analysis using information provided by the referring clinician or laboratory and requests submission of a positive control specimen. Primers are designed and ordered by GeneDx based on the information provided. If the individual being tested is NOT the proband who was previously tested by the outside laboratory, a sample from a related individual known to have the mutation(s) of interest must be provided. Analysis is performed by PCR amplification of the region of interest in the gene using either bi-directional DNA sequencing or another appropriate method.