Other entities represented in this entry:
ORPHA: 79189, 912; DO: 0080478;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 17q12 | Peroxisome biogenesis disorder 3A (Zellweger) | 614859 | Autosomal recessive | 3 | PEX12 | 601758 |
A number sign (#) is used with this entry because this form of Zellweger syndrome (PBD3A) is caused by homozygous or compound heterozygous mutation in the PEX12 gene (601758) on chromosome 17.
The peroxisomal biogenesis disorder (PBD) Zellweger syndrome (ZS) is an autosomal recessive multiple congenital anomaly syndrome resulting from disordered peroxisome biogenesis. 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 3 (CG3) have mutations in the PEX12 gene. For information on the history of PBD complementation groups, see 214100.
Konkol'ova et al. (2015) described a patient with Zellweger syndrome, the son of healthy, nonconsanguineous Caucasian parents. The patient was born by spontaneous delivery at 39 weeks' gestation and had Apgar scores of 4 and 8, with perinatal asphyxia. Dysmorphic features included high forehead, flat face, broad nasal bridge, low-set ears, wide open anterior fontanel, and varus deformity of the left leg. Seizures first occurred on the second day of life. Hypotonia and areflexia were progressive. Abdominal ultrasound revealed polycystic kidneys and a single cyst in the liver. EEG was normal. Ultrasound of the central nervous system disclosed mild dilatation of the ventricular system occipitally. During an enterovirus infection, seizures, bradycardia, and thermolability progressed. The patient died at age 23 days of cardiorespiratory failure.
Chang et al. (1997) found that PEX12 expression restored peroxisomal protein import in fibroblasts from PBD patients of complementation group 3 (CG3) and identified frameshift mutations in PEX12 in 2 unrelated CG3 patients (e.g., 601758.0001).
Okumoto and Fujiki (1997) identified a homozygous nonsense mutation in cells from a patient with Zellweger syndrome of complementation group 3 (601758.0004).
In 2 unrelated patients with Zellweger syndrome of complementation group 3, Okumoto et al. (1998) identified distinct homozygous inactivating mutations in the PEX12 gene (e.g., 601758.0005).
In a patient with Zellweger syndrome who died at age 23 days, Konkol'ova et al. (2015) detected compound heterozygosity for mutations in exon 3 of the PEX12 gene: a 2-bp deletion on the maternal allele (c.887_888delTC; 601758.0011) and a 2-bp duplication on the paternal allele (c.767_768dupAT; 601758.0012.)
Chang, C.-C., Lee, W.-H., Moser, H., Valle, D., Gould, S. J. Isolation of the human PEX12 gene, mutated in group 3 of the peroxisome biogenesis disorders. Nature Genet. 15: 385-388, 1997. [PubMed: 9090384] [Full Text: https://doi.org/10.1038/ng0497-385]
Konkol'ova, J., Petrovic, R., Chandoga, J., Halasova, E., Jungova, P., Bohmer, D. A novel mutation in the PEX12 gene causing a peroxisomal biogenesis disorder. Molec. Biol. Rep. 42: 1359-1363, 2015. [PubMed: 26094004] [Full Text: https://doi.org/10.1007/s11033-015-3885-7]
Okumoto, K., Fujiki, Y. PEX12 encodes an integral membrane protein of peroxisomes. (Letter) Nature Genet. 17: 265-266, 1997. [PubMed: 9354782] [Full Text: https://doi.org/10.1038/ng1197-265]
Okumoto, K., Shimozawa, N., Kawai, A., Tamura, S., Tsukamoto, T., Osumi, T., Moser, H., Wanders, R. J. A., Suzuki, Y., Kondo, N., Fujiki, Y. PEX12, the pathogenic gene of group III Zellweger syndrome: DNA cloning by functional complementation on a CHO cell mutant, patient analysis, and characterization of Pex12p. Molec. Cell. Biol. 18: 4324-4336, 1998. [PubMed: 9632816] [Full Text: https://doi.org/10.1128/MCB.18.7.4324]
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]