Genomic Organization and Characterization of Human PEX2 Encoding a 35-kDa Peroxisomal Membrane Protein

Clinical characterization of a male patient with the recently described 8q21.11 microdeletion syndrome

“…Another important gene deleted in our patient, PEX2, is also deleted in the proband with DA2B and in seven out of the eight patients with ID described by Palomares et al [2011] [Hofmann et al, 2011;Palomares et al, 2011]. This gene has a size of approximately 17.5 kb consisting of 4 exons [Biermanns and Gartner, 2000] and has been associated with peroxisome biogenesis disorders 5 A, also called Zellweger syndrome, (OMIM # 614866) and 5B (OMIM # 614867). The Zellweger syndrome is a severe condition leading frequently to death within the first year of life [Steinberg et al, 2006] and although mildly affected patients may have a mild phenotype characterized by DD, hypotonia, liver dysfunction, sensorineural hearing loss, retinal dystrophy and vision damage [Waterham and Ebberink, 2012], any hypothetical connection between the PEX2 deleted gene and clinical features present in 8q21.11 deletion patients seems unlikely, insofar as, to date, (as in many other autosomal recessive conditions) heterozygous carriers are asymptomatic.…”

“…Despite the association of both ZFHX4 [Hemmi et al, 2006;McMullan et al, 2002] and PEX2 [Biermanns and Gartner, 2000;Steinberg et al, 2006;Waterham and Ebberink, 2012] with neurodevelopment, these genes are deleted in patients with normal cognitive function [McMullan et al, 2002;Hofmann et al, 2011] so that, additional genetic factors within and/or outside the deleted interval and epigenetic and/or environmental modifiers may favor the occurrence of ID in patients with 8q21.11 microdeletions [Palomares et al, 2011;Vulto-van Silfhout et al, 2013] such as in the patient described above.…”

“…A total of 23 genes are located in the interval deleted in our patient, including TMEM70 (Transmembrane Protein 70; OMIM # 612418), related to mitochondrial complex V (ATP synthase) deficiency, nuclear type 2 (OMIM # 614052) [Cizkova et al, 2008], GDAP1 (Ganglioside-Induced Differentiation-Associated Protein 1; OMIM # 606598) that encodes a protein expressed in the central and peripheral nervous system, primarily in Schwann cells and has been implicated in several forms of the Charcot-Marie-Tooth disease (OMIM # 607831, 607706, 608340, and 214400) [Niemann et al, 2005], ZFHX4 (Zinc Finger Homeobox 4; OMIM # 606940), proposed as a candidate gene for congenital bilateral isolated ptosis (OMIM # 178300) [McMullan et al, 2002] and PEX2 (Peroxisome Biogenesis Factor 2; OMIM # 170993) [Biermanns and Gartner, 2000], associated with peroxisomal biogenesis disorders 5 A (OMIM # 614866) and 5B (OMIM # 614867) [Steinberg et al, 2006;Waterham and Ebberink, 2012]. Amongst these 4 genes, only ZFHX4 is included in the deletion found by Hoffman et al [2011] and in the shortest region of overlap described by Palomares et al [2011] [Hofmann et al, 2011;Palomares et al, 2011].…”

Novel Mutations in the PEX2 Gene of Four Unrelated Patients with a Peroxisome Biogenesis Disorder

“…The PEX2 gene was the first gene found to be mutated in ZS and spans approximately 17.5kb in length and contains four exons. The entire coding sequence is included in exon 4 (11). The gene encodes a 305 amino acid protein (PEX2), with a molecular weight of~35 kD.…”