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PEX7 – Adult Refsum disease

Linkage analysis in patients with elevated phytanic acid but lacking PHYH mutations localized a second locus to chromosome 6q22–24, leading to identification of biallelic PEX7 variants in five unrelated adult Refsum disease probands (PMID:12522768). These individuals harbored autosomal recessive LoF alleles such as c.678G>A (p.Trp226Ter), consistent with recessive inheritance and biochemical phenotype.

Biochemical assessment demonstrated impaired phytanic acid α-oxidation, reduced plasmalogen synthesis, and defective import of peroxisomal thiolase in patient cells, corroborating a pathogenic mechanism of PEX7 deficiency (PMID:12522768). This limited but concordant genetic and functional evidence supports PEX7 as a second adult Refsum disease gene. Key take-home: PEX7 sequencing should be included in genetic testing of adult Refsum disease patients negative for PHYH variants to inform diagnosis and management.

References

  • American journal of human genetics • 2003 • Identification of PEX7 as the second gene involved in Refsum disease. PMID:12522768

Evidence Based Scoring (AI generated)

Gene–Disease Association

Limited

Mutations in PEX7 identified in five unrelated probands (PMID:12522768); no segregation data

Genetic Evidence

Limited

Recessive LoF PEX7 variants reported in five probands; no additional family segregation

Functional Evidence

Moderate

Biochemical assays show defective phytanic acid α-oxidation, plasmalogen synthesis, and peroxisomal protein import concordant with RD phenotype (PMID:12522768)