X-linked hypophosphatemia attributable to pseudoexons of the PHEX gene.

Journal article

X-linked hypophosphatemia is commonly caused by mutations of the coding region of PHEX (phosphate-regulating gene with homologies to endopeptidases on the X chromosome). However, such PHEX mutations are not detected in approximately one third of X-linked hypophosphatemia patients who may harbor defects in the noncoding or intronic regions. We have therefore investigated 11 unrelated X-linked hypophosphatemia patients in whom coding region mutations had been excluded, for intronic mutations that may lead to mRNA splicing abnormalities, by the use of lymphoblastoid RNA and RT-PCRs. One X-linked hypophosphatemia patient was found to have 3 abnormally large transcripts, resulting from 51-bp, 100-bp, and 170-bp insertions, all of which would lead to missense peptides and premature termination codons. The origin of these transcripts was a mutation (g to t) at position +1268 of intron 7, which resulted in the occurrence of a high quality novel donor splice site (ggaagg to gtaagg). Splicing between this novel donor splice site and 3 preexisting, but normally silent, acceptor splice sites within intron 7 resulted in the occurrences of the 3 pseudoexons. This represents the first report of PHEX pseudoexons and reveals further the diversity of genetic abnormalities causing X-linked hypophosphatemia.

Authors: Christie, P; Harding, B; Nesbit, M; Whyte, M; Thakker, R

• Publication status: Published
• Journal: Journal of clinical endocrinology and metabolism More from this journal
• Volume: 86
• Issue: 8
• Pages: 3840-3844
• Publication date: 2001-08-01
• DOI: 10.1210/jc.86.8.3840
• EISSN: 1945-7197
• ISSN: 0021-972X
• Language: English
• Keywords: DNA Transposable Elements; Proteins; Male; Cells, Cultured; Reverse Transcriptase Polymerase Chain Reaction; Introns; Exons; Pedigree; PHEX Phosphate Regulating Neutral Endopeptidase; Transcription, Genetic; Hypophosphatemia, Familial; Humans; Female; Lymphocytes