Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (946 page)

   Targeted mutation analysis:

   A panel of four common mutations comprising (legacy mutation name in parenthesis):

•   
p.
N
409S
(
Asn370Ser), p.L483P (Leu444Pro), c.84dupG (84GG), c.115+1G>T, (IVS2
+
1G>A)

•   More extended panels include additional less common mutations such as:

•   
p. V433L (Val394Leu), p.D448H (Asp409His), p.R502C (Arg463Cys), p.R535H (Arg496His), g.5879del55 (1263del55)

   
Confirmatory diagnosis in symptomatic individuals use:

   GBA gene sequence analysis: Analysis of the entire coding region and exon–intron boundaries is useful for identifying rare mutant alleles associated with GD.

   
Prenatal diagnosis
—
when both parental mutations are known use:

   Mutation-specific testing for known familial mutations

   Limitations

   The results of a genetic test may be affected by DNA rearrangements, blood transfusion, bone marrow transplantation, or rare sequence variations.

GENETIC CARRIER TESTING

   Definition

   Parental testing performed to assess carrier status for a specific genetic abnormality. Typically performed on DNA from a blood specimen to test for targeted mutations, but testing also can include other modalities such as enzymatic testing and gel electrophoresis.

   Use

   Carrier testing for autosomal recessive disease (may be targeted to specific ethnic groups). Examples:

   CF: DNA testing for common mutations