Goulding, Jonathan N.;
(2001)
A study on the localisation of the PHEX gene, and mutation analysis of patients with X-linked hypophosphataemic rickets.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
X-linked hypophosphataemic rickets (HYP) is an X-linked dominant disorder that affects 1 in 20000 live births. The disease is characterised by a failure of the kidney to reabsorb phosphate from the glomerular filtrate, resulting in a phosphate leak and hypophosphataemia. The disease had previously been localised to the Xp22.1-22.2 region of the X chromosome, flanked by polymorphic markers DXS43andDXS41. Twenty affected kindreds were screened with an additional eleven polymorphic markers, which localised the gene to a 200-300 kb region in Xp22.1, which lay on a single YAC, A0472. To further order the markers a YAC and cosmid contig from the region were also screened with these markers, with the following marker order deemed the most likely: Xptel - DXS43 - DXS197 - DXS999 - DXS443 - (DXS365, DXS7475, DXS7101) -DXS7474 - DXS7473 - HYP - DXS1683 - DXS1052 - DXS274 - DXS41 - Xcen. Screening Southern blots of patient DNA with cosmids that overlapped YAC A0472, identified a cosmid that showed an altered banding pattern, and therefore a mutation, in two unrelated individuals. This cosmid was sequenced and a candidate gene (PHEX) identified. The gene showed homology at the amino acid level to a family of metalloendopeptidases. To confirm that PHEX was the gene involved in X-linked hypophosphataemic rickets, patient DNA from eighty unrelated families was screened by Single Stranded Conformational Polymorphism (SSCP). A total of twenty three different mutations were identified, which included both deletions and point mutations. This confirmed that PHEX was the gene involved in the HYP disorder.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | A study on the localisation of the PHEX gene, and mutation analysis of patients with X-linked hypophosphataemic rickets |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Thesis digitised by ProQuest. |
| Keywords: | Biological sciences; Rickets |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10100491 |
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