PEX10 – Peroxisome Biogenesis Disorder

PEX10 encodes a peroxisomal membrane RING finger protein essential for matrix protein import. Autosomal recessive PEX10 mutations cause peroxisome biogenesis disorders (PBDs), spanning severe Zellweger syndrome to attenuated ataxic forms. Multiple independent cohorts totaling over 60 probands demonstrate biallelic PEX10 variants with consistent recessive segregation and concordant functional data.

In a Han-Chinese family, three siblings with mild cerebellar ataxia, hyperreflexia, mydriasis and intellectual disability were compound heterozygous for c.2T>C (p.Met1Thr) and c.920G>A (p.Cys307Tyr) in the PEX10 RING domain ([PMID:28320181]).

An Assyrian patient presented sensorineural hearing impairment, tremor and muscle weakness in adolescence due to homozygous c.530T>G (p.Leu177Arg) ([PMID:28784167]).

Three adult French siblings with slowly progressive ataxia and pyramidal signs harbored compound heterozygous missense c.827G>T (p.Cys276Phe) and c.932G>A (p.Arg311Gln) ([PMID:27230853]).

A Japanese series identified a founder homozygous 2-bp deletion c.795_796del (p.Arg265fs) in 11 Zellweger patients, estimating PBD prevalence at ~1/500 000 births ([PMID:12794690]).

Genotype–phenotype correlation in four classical Zellweger and one neonatal adrenoleukodystrophy patient showed severe loss-of-function mutations versus a single H290Q allele in the milder case ([PMID:10862081]).

Functional studies demonstrate that PEX10 interacts with PEX5 and PEX12 via its RING finger; disease-causing mutations disrupt peroxisomal matrix protein import downstream of receptor docking ([PMID:10562279]; [PMID:10837480]).

AR loss-of-function PEX10 variants underlie a definitive gene–disease relationship for PBDs, guiding biochemical, genetic and functional diagnostic strategies. Key take-home: PEX10 sequencing with functional assays enables accurate PBD classification and clinical management.

References

• Journal of the neurological sciences • 2017 • Ataxic form of autosomal recessive PEX10-related peroxisome biogenesis disorders with a novel compound heterozygous gene mutation and characteristic clinical phenotype. PMID:28320181
• Journal of medical case reports • 2017 • Identification of a novel mutation in PEX10 in a patient with attenuated Zellweger spectrum disorder: a case report. PMID:28784167
• Journal of neurology • 2016 • Expanding the spectrum of PEX10-related peroxisomal biogenesis disorders: slowly progressive recessive ataxia. PMID:27230853
• American journal of medical genetics. Part A • 2003 • Genetic heterogeneity of peroxisome biogenesis disorders among Japanese patients: evidence for a founder haplotype for the most common PEX10 gene mutation. PMID:12794690
• Human mutation • 2000 • Phenotype-genotype relationships in PEX10-deficient peroxisome biogenesis disorder patients. PMID:10862081
• The Journal of cell biology • 1999 • PEX12 interacts with PEX5 and PEX10 and acts downstream of receptor docking in peroxisomal matrix protein import. PMID:10562279
• The Journal of biological chemistry • 2000 • Molecular anatomy of the peroxin Pex12p: ring finger domain is essential for Pex12p function and interacts with the peroxisome-targeting signal type 1-receptor Pex5p and a ring peroxin, Pex10p. PMID:10837480

Evidence Based Scoring (AI generated)