The aim of this study was to identify the underlying genetic mutation in patients with hypophosphatemic rickets (HR). The HR patients studied were recruited from a cross-sectional study of 59 HR patients living in Denmark. Genomic DNA was analysed for mutations in PHEX, FGF23, DMP1, SCL34A3 and CLCN5 by polymerase chain reaction (PCR) followed by denaturing high-performance liquid chromatography (dHPLC) analysis. Samples with deviating chromatographic profiles were sequenced in both directions. In addition, a multiplex ligation-dependent probe amplification (MLPA) analysis was performed to detect larger deletions / duplications in PHEX or FGF23. In a total of 24 probands all but one had Danish origin . Familial cases accounted for 12 of the probands while 12 were sporadic. In 20 probands mutations were detected in PHEX of which 12 mutations have not previously been described. In one case a mutation was found in DMP1. Three PHEX mutations were identified by the MLPA analysis only, i.e. two large deletions and one duplication. A novel frame shift mutation in DMP1 was identified in a Lebanese family exhibiting a recessive trait. No mutations were identified in FGF23, SCL34A3 or CLCN5. By the methods used, a disease causing mutation was identified in 83% of the familial and 92% of the sporadic cases, thus, thereby in 88% of the total probands. Genetic analysis performed in HR patients by PCR, dHPLC and sequencing, and in addition by MLPA analysis revealed a high identification rate of gene mutations causing HR, including 12 novel PHEX and one novel DMP1 mutation.
|Status||Udgivet - sep. 2011|
|Begivenhed||50th Annual ESPE meeting - Glasgow, Storbritannien|
Varighed: 25. sep. 2011 → 28. sep. 2011
|Konference||50th Annual ESPE meeting|
|Periode||25/09/2011 → 28/09/2011|