title: Zellweger syndrome caused by PEX13 deficiency: report of two novel mutations.
abstract: Peroxisomal biogenesis disorders represent a group of genetically heterogeneous conditions that have in common failure of proper peroxisomal assembly. Clinically, they are characterized by a spectrum of dysmorphia, neurological, liver, and other organ involvement. To date, mutations in 13 PEX genes encoding peroxins have been identified in patients with peroxisomal biogenesis disorders. Mutations in PEX13, which encodes peroxisomal membrane protein PEX13, are among the least common causes of peroxisomal biogenesis disorders with only three mutations reported so far. Here, we report on two infants whose clinical and biochemical profile was consistent with classical Zellweger syndrome and whose complementation analysis assigned them both to group H of peroxisomal biogenesis disorders. We show that they harbor two novel mutations in PEX13. One patient had a genomic rearrangement resulting in a 147 kb deletion that spans the whole of PEX13, while the other had an out-of-frame deletion of 14 bp. This represents the first report of a PEX13 deletion and suggests that further work is needed to examine the frequency of PEX13 mutations among Arab patients with peroxisomal biogenesis disorders.
authors.affiliation: National Laboratory for Newborn Screening, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors.forename: O Y
authors.initials: OY
authors.lastname: Al-Dirbashi
authors.forename: R
authors.initials: R
authors.lastname: Shaheen
authors.forename: M
authors.initials: M
authors.lastname: Al-Sayed
authors.forename: M
authors.initials: M
authors.lastname: Al-Dosari
authors.forename: N
authors.initials: N
authors.lastname: Makhseed
authors.forename: L
authors.initials: L
authors.lastname: Abu Safieh
authors.forename: T
authors.initials: T
authors.lastname: Santa
authors.forename: B F
authors.initials: BF
authors.lastname: Meyer
authors.forename: N
authors.initials: N
authors.lastname: Shimozawa
authors.forename: F S
authors.initials: FS
authors.lastname: Alkuraya
mesh_terms: D001483:Base Sequence; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D016368:Frameshift Mutation; D015321:Gene Rearrangement; D005816:Genetic Complementation Test; D006801:Humans; D007223:Infant; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics; D008969:Molecular Sequence Data; D017384:Sequence Deletion; D015211:Zellweger Syndrome / Q000235:genetics* / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; C101884:PEX13 protein, human