Genes are listed from most frequent to least frequent genetic cause of ZSD.

See Table A. Genes and Databases for chromosome locus and protein.

Based on complementation studies using somatic cell hybridization and/or cDNA complementation analysis in 810 individuals with biochemical confirmation of ZSD (197 at Kennedy Krieger Institute [unpublished] and 613 reported by Ebberink et al [2011])

See Molecular Genetics for information on variants detected in these genes.

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

An estimate, based on the assumption that large deletions or promoter and deep intronic pathogenic variants would be missed; however, these types of variants do not appear to be common in ZSD.

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

This estimate is based on the number of individuals identified with a PEX1 defect, defined by having two pathogenic PEX1 variants, one of which was a deletion detected by MLPA [Molly Sheridan, PhD; Johns Hopkins DNA Diagnostic Laboratory].

Based on Ebberink et al [2011]. The numerator is the number of individuals belonging to this complementation group who had two pathogenic variants identified and the denominator is the total number of individuals belonging to this complementation group who underwent sequencing of that gene.

One PEX6 variant, p.Arg860Trp, has been associated with ZSD in the heterozygous state due to allelic expression imbalance dependent on allelic background [Falkenberg et al [2017]; see Molecular Genetics.

No data on detection rate of gene-targeted deletion/duplication analysis are available.

PEX11B: single case report [Ebberink et al 2012]. Taylor et al [2017] reported five additional individuals from three families. All had congenital cataracts and other clinical features, but normal or equivocal peroxisomal biomarkers in limited testing.