Mutations in Nance-Horan Syndrome and NHS-A Protein Localization
Author Information
Author(s): Shiwani Sharma, Kathryn P. Burdon, Alpana Dave, Robyn V. Jamieson, Yuval Yaron, Frank Billson, Lionel Van Maldergem, Birgit Lorenz, Jozef Gécz, Jamie E. Craig
Primary Institution: Department of Ophthalmology, Flinders University, Bedford Park, South Australia, Australia
Hypothesis
This study aimed to identify the causative mutations in new patients diagnosed with Nance-Horan syndrome and to investigate the effect of mutations on subcellular localization of the NHS-A protein.
Conclusion
The mislocalization of the mutant NHS-A protein is expected to adversely affect cell-cell junctions in epithelial cells, which may explain cataractogenesis in Nance-Horan syndrome patients.
Supporting Evidence
- Truncating mutations were found in 6 out of 10 unrelated patients.
- Each of four patients carried a novel mutation, while two others had previously reported mutations.
- All three mutant proteins failed to localize to the cellular periphery and were found in the cytoplasm.
Takeaway
Researchers found new mutations in a gene linked to a condition that causes cataracts and dental issues, and these mutations affect how the protein behaves in cells.
Methodology
All coding exons of NHS were screened for mutations by PCR and sequencing, and the expression and localization of mutant proteins were determined in mammalian epithelial cells.
Limitations
Mutations were identified in only 60% of patients, and some patients with clinical features consistent with NHS had no identified mutations.
Participant Demographics
The study included 10 male individuals diagnosed with Nance-Horan syndrome from four countries.
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