Other entities represented in this entry:
ORPHA: 79189, 912; DO: 0080479;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 6p21.1 | Peroxisome biogenesis disorder 4A (Zellweger) | 614862 | Autosomal recessive | 3 | PEX6 | 601498 |
A number sign (#) is used with this entry because of evidence that this form of Zellweger syndrome (PBD4A) is caused by homozygous or compound heterozygous mutation in the PEX6 gene (601498) on chromosome 6p21.1.
Mutations in the PEX6 gene also cause the milder phenotypes peroxisome biogenesis disorder-4B (PBD4B; 614863) and Heimler syndrome-2 (HMLR2; 616617).
The peroxisomal biogenesis disorder (PBD) Zellweger syndrome (ZS) is an autosomal recessive multiple congenital anomaly syndrome. Affected children present in the newborn period with profound hypotonia, seizures, and inability to feed. Characteristic craniofacial anomalies, eye abnormalities, neuronal migration defects, hepatomegaly, and chondrodysplasia punctata are present. Children with this condition do not show any significant development and usually die in the first year of life (summary by Steinberg et al., 2006).
For a complete phenotypic description and a discussion of genetic heterogeneity of Zellweger syndrome, see 214100.
Individuals with PBDs of complementation group 4 (CG4, equivalent to CG6 and CGC) have mutations in the PEX6 gene. For information on the history of PBD complementation groups, see 214100.
Fukuda et al. (1996) described a patient with Zellweger syndrome of complementation group C, a Japanese girl of nonconsanguineous parents. In the neonatal period she showed severe asphyxia, profound hypotonia, and clonic convulsions. Cranial dysmorphism including low nasal bridge, hypertelorism, epicanthus inversus, and upslanting palpebral fissures, as well as hepatomegaly, were present. X-rays showed abnormal calcific stippling of both patellae. Serum VLCFAs were elevated. Immunohistochemical staining of cultured fibroblasts indicated absence of peroxisomes. The patient died of respiratory failure at 7 months.
Yahraus et al. (1996) observed that expression of PXAAA1 (PEX6; 601498) restored peroxisomal protein import in fibroblasts from 16 unrelated members of complementation group 4 of the peroxisomal biogenesis disorders (PBDs). They identified compound heterozygosity for mutation in the PEX6 gene (601498.0001, 601498.0002) in a patient of complementation group 4.
In 2 patients with Zellweger syndrome of complementation group C, Fukuda et al. (1996) identified mutations in the PEX6 gene (601498.0003, 601498.0004).
Fukuda, S., Shimozawa, N., Suzuki, Y., Zhang, Z., Tomatsu, S., Tsukamoto, T., Hashiguchi, N., Osumi, T., Masuno, M., Imaizumi, K., Kuroki, Y., Fujiki, Y., Orii, T., Kondo, N. Human peroxisome assembly factor-2 (PAF-2): a gene responsible for group C peroxisome biogenesis disorder in humans. Am. J. Hum. Genet. 59: 1210-1220, 1996. [PubMed: 8940266]
Steinberg, S. J., Dodt, G., Raymond, G. V., Braverman, N. E., Moser, A. B., Moser, H. W. Peroxisome biogenesis disorders. Biochim. Biophys. Acta 1763: 1733-1748, 2006. [PubMed: 17055079] [Full Text: https://doi.org/10.1016/j.bbamcr.2006.09.010]
Yahraus, T., Braverman, N., Dodt, G., Kalish, J. E., Morrell, J. C., Moser, H. W., Valle, D., Gould, S. J. The peroxisome biogenesis disorder group 4 gene, PXAAA1, encodes a cytoplasmic ATPase required for stability of the PTS1 receptor. EMBO J. 15: 2914-2923, 1996. [PubMed: 8670792]