Table 1.

Summary of Molecular Genetic Testing Used in Niemann-Pick Disease Type C

Gene 1Proportion of NPC Attributed to Mutation of This Gene 2Test MethodVariants Detected 3Variant Detection Frequency by Gene and Test Method 4
NPC190% 5Sequence analysis 6Sequence variants80%-90% 7
Deletion/duplication analysis 8Partial- and whole-gene deletionsUnknown 9
Targeted analysis for pathogenic variantsVary panels differ by laboratoryVary 10
NPC24%Sequence analysis 6Sequence variantsClose to 100%
Deletion/duplication analysis 8Partial- and whole-gene deletionsUnknown; none reported 11
Targeted analysis for pathogenic variantsVariant panels differ by laboratoryVary

Percent of individuals with NPC who have at least one identifiable pathogenic variant [Greer et al 1999, Yamamoto et al 1999, Park et al 2003] using a variant scanning testing method


See Molecular Genetics for information on allelic variants.


The ability of the test method used to detect a variant that is present in the indicated gene


Detection rates using sequence analysis may be comparable to those found using scanning for pathogenic variants, which has identified NPC1 variants in 90% of affected individuals [Park et al 2003, Patterson et al 2012].


Examples of pathogenic variants detected by sequence analysis may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.


Most individuals with NPC1 are compound heterozygotes with pathogenic variants unique to their family; to date, pathogenic variants in one or both NPC1 alleles cannot be identified in a substantial number of cases [Greer et al 1999, Yamamoto et al 1999, Park et al 2003].


Testing that identifies deletions/duplications not readily detectable by sequence analysis of the coding and flanking intronic regions of genomic DNA; included in the variety of methods that may be used are: quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and chromosomal microarray (CMA) that includes this gene/chromosome segment.


Few have been reported; the frequency of such variants may be rare.


Of note, individuals with NPC1 from Nova Scotia (previously said to have Niemann-Pick type D) almost uniformly have the p.Gly992Trp variant [Greer et al 1998].


No large insertions or deletions have been reported in NPC2. Based on the high sensitivity of the NPC2 sequencing test, a screening test for large deletions/duplications may have a very low yield.

From: Niemann-Pick Disease Type C

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