Other entities represented in this entry:
ORPHA: 79189, 912; DO: 0080480;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 8q21.13 | Peroxisome biogenesis disorder 5A (Zellweger) | 614866 | Autosomal recessive | 3 | PEX2 | 170993 |
A number sign (#) is used with this entry because this form of Zellweger syndrome (PBD5A) is caused by homozygous mutation in the PEX2 gene (170993) on chromosome 8q21.
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 5 (CG5, equivalent to CG10 and CGF) have mutations in the PEX2 gene. For information on the history of PBD complementation groups, see 214100.
Shimozawa et al. (1992) studied a Japanese girl (M.M.), aged 8 months, with typical clinical findings of Zellweger syndrome as well as accumulation of very long chain fatty acids in serum, absence of liver homogenates in all 3 peroxisomal beta-oxidation enzymes, absent peroxisomes in skin fibroblasts, and, at autopsy, macrogyria and polymicrogyria in the brain, hepatosplenomegaly, and many small cysts in the renal cortices bilaterally.
In a Japanese patient (M.M.) with Zellweger syndrome, Shimozawa et al. (1992) identified a homozygous nonsense mutation in the PEX2 gene (170993.0001). Shimozawa et al. (1993) identified this mutation in a Dutch patient with Zellweger syndrome.
In 3 patients with Zellweger syndrome, Gootjes et al. (2004) identified homozygous mutations in the PEX2 gene (170993.0001-170993.0003).
Gootjes, J., Elpeleg, O., Eyskens, F., Mandel, H., Mitanchez, D., Shimozawa, N., Suzuki, Y., Waterham, H. R., Wanders, R. J. A. Novel mutations in the PEX2 gene of four unrelated patients with a peroxisome biogenesis disorder. Pediat. Res. 55: 431-436, 2004. [PubMed: 14630978] [Full Text: https://doi.org/10.1203/01.PDR.0000106862.83469.8D]
Shimozawa, N., Suzuki, Y., Orii, T., Moser, A., Moser, H. W., Wanders, R. J. A. Standardization of complementation grouping of peroxisome-deficient disorders and the second Zellweger patient with peroxisomal assembly factor-1 (PAF-1) defect. (Letter) Am. J. Hum. Genet. 52: 843-844, 1993. [PubMed: 7681622]
Shimozawa, N., Tsukamoto, T., Suzuki, Y., Orii, T., Shirayoshi, Y., Mori, T., Fujiki, Y. A human gene responsible for Zellweger syndrome that affects peroxisome assembly. Science 255: 1132-1134, 1992. [PubMed: 1546315] [Full Text: https://doi.org/10.1126/science.1546315]
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]