Biochemical and genetic characterization of an unusual mild PEX3-related Zellweger spectrum disorder

Kathrine Bjørgo; Roar Fjær; Hanne Håberg Mørk; Sacha Ferdinandusse; Kim D Falkenberg; Hans R Waterham; Ane-Marte Øye; Alma Sikiric; Silja Svanstrøm Amundsen; Mari Ann Kulseth; Kaja Selmer

doi:10.1016/j.ymgme.2017.06.004

Biochemical and genetic characterization of an unusual mild PEX3-related Zellweger spectrum disorder

Mol Genet Metab. 2017 Aug;121(4):325-328. doi: 10.1016/j.ymgme.2017.06.004. Epub 2017 Jun 17.

Authors

Affiliations

¹ Department of Medical Genetics, Oslo University Hospital, P.B 4956 Nydalen, 0424 Oslo, Norway. Electronic address: uxatjr@ous-hf.no.
² Department of Medical Genetics, Oslo University Hospital, P.B 4956 Nydalen, 0424 Oslo, Norway. Electronic address: roar.fjar@medisin.uio.no.
³ Department of Medical Genetics, Oslo University Hospital, P.B 4956 Nydalen, 0424 Oslo, Norway. Electronic address: UXMRHC@ous-hf.no.
⁴ Laboratory Genetic Metabolic Diseases, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. Electronic address: s.ferdinandusse@amc.uva.nl.
⁵ Laboratory Genetic Metabolic Diseases, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. Electronic address: k.d.falkenberg@amc.uva.nl.
⁶ Laboratory Genetic Metabolic Diseases, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. Electronic address: h.r.waterham@amc.uva.nl.
⁷ Department of Medical Genetics, Oslo University Hospital, P.B 4956 Nydalen, 0424 Oslo, Norway. Electronic address: UXYEAA@ous-hf.no.
⁸ Department of Neurohabilitation, Oslo University Hospital, P.B 4956 Nydalen, 0424 Oslo, Norway. Electronic address: UXALSI@ous-hf.no.
⁹ Department of Medical Genetics, Oslo University Hospital, P.B 4956 Nydalen, 0424 Oslo, Norway. Electronic address: sisvam@ous-hf.no.
¹⁰ Department of Medical Genetics, Oslo University Hospital, P.B 4956 Nydalen, 0424 Oslo, Norway. Electronic address: makulset@ous-hf.no.
¹¹ Department of Medical Genetics, Oslo University Hospital, P.B 4956 Nydalen, 0424 Oslo, Norway. Electronic address: k.k.selmer@medisin.uio.no.

PMID: 28673549
DOI: 10.1016/j.ymgme.2017.06.004

Abstract

Patients with PEX3 mutations usually present with a severe form of Zellweger spectrum disorder with death in the first year of life. Whole exome sequencing in adult siblings with intellectual disability revealed a homozygous variant in PEX3 that abolishes the normal splice site. A cryptic acceptor splice site is activated and an in-frame transcript with a deletion is produced. This transcript translates into a protein with residual activity explaining the relatively mild peroxisomal abnormalities and clinical phenotype.

Keywords: Cryptic splice site; PEX genes; PEX3; Peroxisomal biogenesis disorder; Zellweger spectrum disorder; Zellweger syndrome.

Publication types

Case Reports

MeSH terms

Adult
Family
Female
Homozygote
Humans
Lipoproteins / genetics*
Male
Membrane Proteins / genetics*
Mutation
Peroxins / genetics*
Peroxisomes / physiology
Phenotype
RNA Splice Sites
Sequence Deletion
Zellweger Syndrome / genetics*
Zellweger Syndrome / metabolism*

Substances

Lipoproteins
Membrane Proteins
Peroxins
Pex3 protein, human
RNA Splice Sites