Genomic organization of the human PEX gene mutated in X-linked dominant hypophosphatemic rickets

Fiona Francis, Tim M. Strom, Steffen Hennig, Annett Böddrich, Bettina Lorenz, Oliver Brandau, Klaus L. Mohnike, Michele Cagnoli, Christina Steffens, Sven Klages, Katja Borzym, Thomas Pohl, Claudine Oudet, Michael J. Econs, Peter S.N. Rowe, Richard Reinhardt, Thomas Meitinger, Hans Lehrach

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126 Scopus citations


X-linked dominant hypophosphatemic rickets (HYP) is the most common form of hereditary rickets. Recently we have cloned the PEX gene and shown it to be mutated and deleted in HYP individuals. We have now completely sequenced a 243-kb genomic region containing PEX and have identified all intron-exon boundary sequences. We show that PEX, homologous to members of a neutral endopeptidase family, has an exon organization that is very similar to neprilysin. We have performed an extensive mutation analysis examining all 22 PEX coding exons in 29 familial and 14 sporadic cases of hypophosphatemia. Sequence changes include missense, frameshift, nonsense, and splice site mutations and intragenic deletions. A mutation was found in 25 (86%) of the 29 familial cases and 8 (57%) of the 14 sporadic cases. Our data provide the first evidence that most of the familial and also a large number of the sporadic cases of hypophosphatemia are caused by loss-of-function mutations in PEX.

Original languageEnglish (US)
Pages (from-to)573-585
Number of pages13
JournalGenome research
Issue number6
StatePublished - Jun 1997


ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Francis, F., Strom, T. M., Hennig, S., Böddrich, A., Lorenz, B., Brandau, O., Mohnike, K. L., Cagnoli, M., Steffens, C., Klages, S., Borzym, K., Pohl, T., Oudet, C., Econs, M. J., Rowe, P. S. N., Reinhardt, R., Meitinger, T., & Lehrach, H. (1997). Genomic organization of the human PEX gene mutated in X-linked dominant hypophosphatemic rickets. Genome research, 7(6), 573-585.