Other entities represented in this entry:
ORPHA: 79189, 912; DO: 0080482;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 22q11.21 | Peroxisome biogenesis disorder 7A (Zellweger) | 614872 | Autosomal recessive | 3 | PEX26 | 608666 |
A number sign (#) is used with this entry because this form of Zellweger syndrome (PBD7A) is caused by homozygous or compound heterozygous mutation in the PEX26 gene (608666) on chromosome 22q11.
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 8 (CG8, equivalent to CGA) have mutations in the PEX26 gene. For information on the history of PBD complementation groups, see 214100.
Al-Sayed et al. (2007) described a child with Zellweger syndrome who was one of 4 affected sibs. He had typical features of Zellweger syndrome including high forehead, flat face, large anterior and posterior fontanels, flat occiput, posteriorly rotated and low-set ears, nystagmus, bilateral lenticular cataract, jaundice, high-arched palate, long philtrum, bilateral talipes equinovarus, and severe hypotonia. Magnetic resonance imaging (MRI) of the brain revealed bilateral cortical polymicrogyria. Very long chain fatty acids (VLCFAs) were elevated. The child died at 4 months of age from cardiorespiratory arrest after a chest infection. The parents had sought preimplantation genetic analysis with intracytoplasmic sperm injection (ICSI), which resulted in the birth of a healthy girl.
Matsumoto et al. (2003) studied 4 unrelated patients with Zellweger syndrome. Three were homozygous for mutations and one was a compound heterozygote (see 608666.0002-608666.0004).
Weller et al. (2005) identified patients with Zellweger syndrome and mutations in the PEX26 gene (608666.0008, 608666.0009).
Al-Sayed, M., Al-Hassan, S., Rashed, M., Qeba, M., Coskun, S. Preimplantation genetic diagnosis for Zellweger syndrome. Fertil. Steril. 87: 1468.e1-1468.e3, 2007. [PubMed: 17336976] [Full Text: https://doi.org/10.1016/j.fertnstert.2006.09.014]
Matsumoto, N., Tamura, S., Furuki, S., Miyata, N., Moser, A., Shimozawa, N., Moser, H. W., Suzuki, Y., Kondo, N., Fujiki, Y. Mutations in novel peroxin gene PEX26 that cause peroxisome-biogenesis disorders of complementation group 8 provide a genotype-phenotype correlation. Am. J. Hum. Genet. 73: 233-246, 2003. [PubMed: 12851857] [Full Text: https://doi.org/10.1086/377004]
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]
Weller, S., Cajigas, I., Morrell, J., Obie, C., Steel, G., Gould, S. J., Valle, D. Alternative splicing suggests extended function of PEX26 in peroxisome biogenesis. Am. J. Hum. Genet. 76: 987-1007, 2005. [PubMed: 15858711] [Full Text: https://doi.org/10.1086/430637]