Bjørgo Kathrine, Fjær Roar, Mørk Hanne Håberg, Ferdinandusse Sacha, Falkenberg Kim D, Waterham Hans R, Øye Ane-Marte, Sikiric Alma, Amundsen Silja Svanstrøm, Kulseth Mari Ann, Selmer Kaja
Department of Medical Genetics, Oslo University Hospital, P.B 4956 Nydalen, 0424 Oslo, Norway.
Laboratory Genetic Metabolic Diseases, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
Mol Genet Metab. 2017 Aug;121(4):325-328. doi: 10.1016/j.ymgme.2017.06.004. Epub 2017 Jun 17.
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.
患有PEX3突变的患者通常表现为严重形式的泽尔韦格谱系障碍，在出生后第一年死亡。对患有智力残疾的成年兄弟姐妹进行的全外显子组测序显示，PEX3中存在一个纯合变异，该变异消除了正常的剪接位点。一个隐蔽的剪接受体位点被激活，产生了一个带有缺失的框内转录本。该转录本翻译成具有残余活性的蛋白质，这解释了相对较轻的过氧化物酶体异常和临床表型。
