Journal Article

Mutations in <i>PEX10</i> Is the Cause of Zellweger Peroxisome Deficiency Syndrome of Complementation Group B

Kanji Okumoto, Ryota Itoh, Nobuyuki Shimozawa, Yasuyuki Suzuki, Shigehiko Tamura, Naomi Kondo and Yukio Fujiki

in Human Molecular Genetics

Volume 7, issue 9, pages 1399-1405
Published in print September 1998 | ISSN: 0964-6906
Published online September 1998 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/7.9.1399
Mutations in PEX10 Is the Cause of Zellweger Peroxisome Deficiency Syndrome of Complementation Group B

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Peroxisome biogenesis disorders (PBD), such as Zellweger syndrome, are autosomal recessive diseases caused by a deficiency in peroxisome assembly as well as a malfunction of the peroxisomes, where at least 10 genotypes have been reported. We have isolated a human PEX10 cDNA (HsPEX10) by an expressed sequence tag homology search on a human DNA database using yeast PEX10 from Hansenula polymorpha, followed by screening of a human liver cDNA library. This cDNA encodes a peroxisomal protein (a peroxin Pex10p) comprising 326 amino acids, with two putative transmembrane segments and a C3HC4 zinc finger RING motif. Both the N- and C-terminal regions of Pex10p are exposed to the cytosol, as assessed by an expression study of epitope-tagged Pex10p. HsPEX10 expression morphologically and biochemically restored peroxisome biogenesis in fibroblasts from Zellweger patients of complementation group B in Japan (complementation group VII in the USA). One patient (PBDB-01) possessed a homozygous, inactivating mutation, a 2 bp deletion immediately upstream of the RING motif, which resulted in a frameshift, altering 65 amino acids from the normal. This implies that the C-terminal part, including the RING finger, is required for biological function of Pex10p. PEX10 cDNA derived from patient PBDB-01 was defective in peroxisome-restoring activity when expressed in patient fibroblasts. These results demonstrate that mutation in PEX10 is the genetic cause of complementation group B PBD.

Journal Article.  4383 words.  Illustrated.

Subjects: Genetics and Genomics

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