Table 1.

Summary of Molecular Genetic Testing Used in Propionic Acidemia

Gene 1Proportion of PA Attributed to Pathogenic Variants in This GeneProportion of Pathogenic Variants 2 Detected by Test Method 3
Sequence analysis 4Gene-targeted deletion/duplication analysis 5
PCCA50%78%18% 6
PCCB50%97%3% 7

See Molecular Genetics for information on allelic variants detected in this gene.


Kraus et al [2012] reported no identifiable pathogenic variants in 7% (4/54) and one identifiable variant in 4% (2/54) of individuals with propionic acidemia. Some of the variants may have escaped detection by existing sequencing methods, but could have been detected by copy number analysis [Kraus et al 2012]. Desviat et al [2009] reported that only 1.5% of individuals with PCCA-related PA could not be characterized molecularly, when analyzed using both sequencing and copy number analysis [Desviat et al 2009].


Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Pathogenic variants 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.


Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods that may be used can include: quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single exon deletions or duplications.


Exon deletions account for to ~20% of PCCA disease-causing alleles [Yang et al 2004, Kaya et al 2008, Desviat et al 2009, Aradhya et al 2012].


Three PCCB large-deletion alleles have been described [Desviat et al 2006, Kraus et al 2012, Chiu et al 2014].

From: Propionic Acidemia

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