Turkish Scientists Identify a Novel Mutation in a Rare Disease Study

 The findings were published in the international peer-reviewed scientific journal Life. The study reports the discovery of a novel mutation in the patient’s SIL1 gene, designated as c.453+1G>T, which has not been documented in any existing genetic database.

The research, led by Biruni University, highlights a significant genetic discovery. The study team included Associate Professor Elif Sibel Aslan, Sajjad Eslamkhah, Assistant Professor Nermin Akçalı, Assistant Professor Cüneyd Yavaş, Associate Professor Lütfiye Karcıoğlu Batur, Dr. Esma Sengenç, and Biruni University Rector Professor Adnan Yüksel.

The case analyzed in the study involved a patient who has been under the long-term clinical supervision of Professor Adnan Yüksel. By integrating detailed clinical observations with advanced genetic analyses, the researchers were able to comprehensively clarify the molecular basis of the disease.

“Understanding Rare Diseases Requires a Multidisciplinary Approach”

Commenting on the study, Professor Adnan Yüksel emphasized the importance of combining clinical follow-up with genetic research:

“In rare diseases such as Marinesco-Sjögren Syndrome, reaching an accurate diagnosis is only possible when clinical findings are evaluated alongside advanced genetic analyses. In this case, being able to further explain our patient’s long-observed clinical features at the genetic level is extremely valuable, both for patient management and for expanding scientific knowledge.”

Professor Yüksel also noted that the findings may not only benefit this single case but could provide guidance for other individuals facing similar rare conditions.

A Previously Unreported Genetic Variant

Professor Yüksel stated that the newly identified mutation in the SIL1 gene c.453+1G>T has never been reported in any genetic database to date.

“Comprehensive analyses of all protein-coding genes, together with computer-assisted genetic evaluations, indicate that this alteration disrupts the normal structure of the protein and significantly affects the protein-folding process within the cell,” he explained.

Structural modeling studies further demonstrated that the mutation leads to a shortened and functionally impaired SIL1 protein. This dysfunction is believed to result in the accumulation of misfolded proteins within cells, ultimately triggering the clinical manifestations of the disease.

Clinical Findings Align with Genetic Results

Associate Professor Elif Sibel Aslan from the Department of Molecular Biology and Genetics at Biruni University’s Faculty of Engineering and Natural Sciences reported that the patient exhibited hallmark clinical features of Marinesco-Sjögren Syndrome, including congenital cataracts, balance and gait disturbances, muscle weakness, and skeletal deformities. She stated that the newly identified genetic variant strongly explains the patient’s clinical presentation.

Laying the Groundwork for Targeted Therapies

Highlighting the rarity of Marinesco-Sjögren Syndrome worldwide, Dr. Aslan noted that in many cases the underlying genetic causes remain unclear. “By expanding the mutation spectrum of the SIL1 gene, this study contributes significantly to the genetic diagnosis of rare diseases and may pave the way for earlier diagnosis, improved genetic counseling, and the development of targeted therapies in the future,” she said.

Dr. Aslan emphasized that integrating genetic analyses with clinical monitoring plays a critical role in diagnosing and understanding rare diseases. “Uncovering the molecular and genetic mechanisms underlying these conditions will ultimately enable the development of therapies at the molecular level,” she added.

Following this study, researchers plan to pursue advanced methods aimed at reducing the cellular impact of the disease-causing gene. One proposed approach involves administering a laboratory-developed, functional mRNA designed to counteract the defective gene’s effects. This therapy would be delivered through regular, controlled daily injections similar in practice to insulin administration.