In recent years, an increasing number of inherited diseases, of previously unknown aetiology, have been shown to arise from defects in the structure and function of primary cilia. Cilia play important roles in many physiological processes, including cell and fluid movement, development and chemo-, . mechano-, and photosensation. Ciliopathies now comprise a broad set of developmental and adult phenotypes including polycystic kidneys, CNS anomalies such as hydrocephalus and some forms of retinal dystrophy. Functional candidates for Meckel-Gruber syndrome were screened in a cohort using high resolution melt curve analysis and the utility of the technique is further demonstrated by genotyping a rare polymorphism in RPGRlPlL in ciliopathy patients. Mutations in TMEM216 are shown to cause Meckel-Gruber syndrome type 2 and it is demonstrated that cilia are lost in patients with these mutations. It is also shown that, like other ciliopathy proteins, TMEM216 localises to the primary cilium and interacts with key players of the noncanonical Wnt signalling pathway. Further work aimed to elucidate the molecular genetics of Ivemark syndrome, a possible ciliopathy in which patients are affected by disorders of symmetry.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:598033 |
| Date | January 2012 |
| Creators | Logan, Clare Victoria |
| Publisher | University of Leeds |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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