In sight
Scientists have discovered a gene for hereditary blindness
The disease is caused by a mutation, due to which an important protein ceases to be produced
Denis Gritsenko, Izvestia
We are talking about the causes of Leber's hereditary optical neuropathy, a rare disease that leads to complete loss of vision. Until recently, the genetic causes of its occurrence in 24% of cases were not completely clear. Scientists have found out that visual impairment can develop due to a mutation in the DNAJC30 gene. Studies have shown that there are more carriers of this mutant gene among the residents of Russia than in other countries. But knowing the causes will allow you to more accurately diagnose the disease, and in the future create a cure for it.
The wrong gene
An international group of biochemists, geneticists and ophthalmologists from 34 scientific organizations has completed a study on the mechanisms of the occurrence of hereditary optical neuropathy Leber. The work was also attended by specialists of the Medical and Genetic Scientific Center named after Academician N.P. Bochkov. This was told to Izvestia by the Ministry of Science and Higher Education of the Russian Federation.
Leber's neuropathy occurs with a frequency of one case per 30 thousand people and leads to loss of central vision in both eyes.
- 24% of patients with a clinical diagnosis of "hereditary optical neuropathy" until recently remained without genetic verification of the diagnosis, without understanding the nature of their visual impairment and the need to receive treatment that differs from therapy for optical neuropathies of another genesis, – explained the chief researcher of the Department of Pathology of the retina and optic nerve of the FGBNU "Scientific Research Institute of Eye Diseases" (NIIGB) Natalia Sheremet.
Scientists have found out that in some cases the cause of the disease is mutations in the DNAJC30 gene. Previously, the role of this gene remained unknown. It turned out that its product, the DNAJC30 protein, performs the function of a chaperone in the mitochondrial respiratory chain, that is, it helps to properly organize the spatial configuration of the polypeptide chain. The absence of the DNAJC30 protein due to a mutation of the gene leads to the accumulation of non-functional proteins in the mitochondria. This disrupts the respiratory chain of mitochondria of cells, which leads to the development of the clinical picture of the disease.
– Imagine a shoe with laces. It looks like one of the main protein complexes in mitochondria. The laces wear out, and they need to be changed in time. The DNAJC30 protein is responsible for the timely change of the "shoelaces" in the mitochondrial "shoe". This is necessary so that the mitochondria are fresh and full of energy again," explained Polina Tsygankova, senior researcher at the Laboratory of Hereditary Metabolic Diseases of the Academician N.P. Bochkov Moscow State Medical Center.
During the study, scientists sequenced (decrypted) the exome of patients with an unconfirmed diagnosis. An exome is a set of all genes encoding proteins. The sample included 33 patients with clinical manifestations of Leber neuropathy, of which 16 were identified in Russia.
The described mutation of the DNAJC30 gene is characteristic of Eastern European populations, which presumably formed 85 generations ago. Studies have shown that there are more DNAJC30 carriers among the Russian population than in other countries. The mutation is inherited by an autosomal recessive type, that is, the parents of patients remain its healthy carriers, and a child who receives one damaged copy of the gene from each of them becomes ill. The average age of onset of the disease is 28 years. In men, it manifests itself five times more often than in women.
The first step
The study of the nature of the disease makes it possible to understand and predict the possibilities of its treatment with the help of gene therapy, explained Boris Malyugin, Deputy Director General for Scientific Work of the National Medical Research Center for Eye Microsurgery named after Academician S.N. Fedorov, Chairman of the Society of Ophthalmologists of Russia.
"By identifying the gene, we are taking the first step on this long journey," he explained.
In some patients, there were no changes in mitochondrial DNA, which are present in most patients. At the same time, all signs of the disease were phenotypically manifested. Now scientists have found the reason, which was mutations in the DNAJC30 gene, the specialist noted.
– Since this variant of the disease is monogenic, that is, caused by the loss of functionality of one protein due to mutations in the corresponding gene, the disease will be suitable for therapy based on adeno-associated viruses. It allows you to deliver a corrected copy of the "missing" gene and return its functionality," said Evgeny Kegeles, an employee of the laboratory of genomic engineering at MIPT (a university participating in the project to increase the competitiveness of education "5-100").
According to the expert, this approach is the main method of gene therapy, it shows promising results not only in trials, but also in clinics. For example, the drug Luxturna is used to treat Leber's congenital amaurosis, the specialist said.
The results of the study can already be used by geneticists consulting couples in whose families Leber's neuropathy occurs, said Madina Azova, Head of the Department of Biology and General Genetics of the RUDN.
– During genotyping, not only mitochondrial DNA, but also the DNAJC30 gene should be examined for mutations, – she believes.
It is worth continuing work on genome sequencing in case of suspicion of common eye pathologies having a genetic basis, said Rinat Fayzrakhmanov, head of the Center for Ophthalmology at the Pirogov Center.
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