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Researchers narrow hunt for keratoconus gene
A region in the genome where the mutated gene is probably located has been identified, researcher says.
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BARCELONA – Researchers hope to discover the keratoconus gene soon, according to François Malecaze, MD.
“We have identified a region in the genome where the mutated gene of keratoconus is probably located. The next step will be to sequence the suspected gene in order to find the mutated nucleotide, which will be a definite indication that this is the gene we were looking for,” Dr. Malecaze said during an instructional course at the winter meeting of the European Society of Cataract and Refractive Surgeons.
The discovery of the keratoconus gene will affect the diagnosis and treatment of the disease. It could also help solve one of the problems in selecting patients for refractive surgery, he said.
Important consequences
Dr. Malecaze said there are four reasons that make the search for the keratoconus gene a major goal in ophthalmology.
“The first reason is because keratoconus is often familial. Previous studies suggested that 10% of keratoconus cases have a familial connection. However, more recent studies that take into account forme fruste keratoconus have shown that the prevalence of familial keratoconus is higher,” he said.
The second reason is because the pathogenesis of keratoconus is still unknown. The classical biochemical strategies to find the cause of the disease have not been successful so far, and genetics might explain the phenomena underlying this kind of corneal deformation, he said.
“The third reason is that the discovery of the keratoconus gene will dramatically improve the diagnosis of the disease, which is not always an easy task,” Dr. Malecaze said.
In some cases, even the most sophisticated corneal topographers do not guarantee a reliable differential diagnosis between forme fruste keratoconus and pseudokeratoconus.
“Even the quantitative indices don’t always allow a clear-cut decision, which is crucial when we screen patients for refractive surgery,” he pointed out.
In the literature, most cases of post-LASIK ectasia were reported in connection with topographically suspected keratoconus corneas.
“In the future, once the gene of keratoconus is discovered, a simple blood sample will allow a diagnostic decision,” Dr. Malecaze said.
Last, this discovery will lead to new, more specific therapeutic strategies that are based on a better knowledge of the biology and pathophysiology of the disease, he said.
Familial cases
Dr. Malecaze’s search for the keratoconus gene is part of a European project involving several centers in France and one center in Spain.
The first stage of the study consisted of recruiting a large number of families in which at least two cases of keratoconus had been diagnosed. The second step involved performing a linkage analysis.
“The principle of linkage analysis is to localize in the genome the region containing the mutating gene. In order to do this, we use markers which are distributed over the entire genome and find the markers which are transmitted with keratoconus,” Dr. Malecaze explained. “Once this region has been delimited, all the genes that are contained within its boundaries are screened for mutations. This is done by comparing the single nucleotides contained in the genes of keratoconus patients with those contained in the genes of healthy people. If one of the nucleotides is mutated, then you have found the keratoconus gene.”
The keratoconus gene has not yet been found, but a region that is likely to contain the mutated gene has been localized.
“We have found a region which contains the gene responsible for 70% of the European familial keratoconus cases,” Dr. Malecaze said. “It is difficult to say when the actual gene will be identified.”
Dr. Malecaze said that if more families are included in the study, the chance of the gene being discovered soon is greater.
“If you have keratoconus families to add to our list, please do not hesitate to contact us,” he told physicians at the meeting.
For Your Information:
- François Malecaze, MD, can be reached at Service d’Ophthalmologie, CHU Toulouse - Hôpital de Purpan, 31059 Toulouse Cédex, France; +33-5-61-77-74-04; fax: +33-5-61-77-24-45; e-mail: malecaze.fr@chu-toulouse.fr.