Rare Diseases and Clinical Genetics

The Mission: Decoding Diseases That Almost No One Knows About

Rare diseases present one of the most complex challenges in medicine. They encompass thousands of different medical conditions, some of which are known only to a small community of physicians and researchers. Given their infrequency and intricate nature, diagnosing these diseases requires a combination of clinical expertise, advanced genetic testing, and comparison with similar cases in Israel and around the world.

Although each rare disease affects only a small number of people, taken together they represent a widespread phenomenon. In Israel alone, about half a million people live with rare genetic diseases, and worldwide the number exceeds 300 million. This is where clinical genetics comes in, a groundbreaking field that bridges practical medicine, molecular genetics, and advanced sequencing technologies. Its goal is to identify the cause of a disease, understand how it affects the body, assess familial risks, and enable early diagnosis, prevention, and, in some cases, the development of more precisely tailored treatments.

What Are Rare Diseases?

In many countries, a rare disease is defined as a condition that affects fewer than one in every 2,000 people. Behind this statistical definition, however, lies a broad and diverse range of medical conditions, including metabolic diseases, neurological disorders, immune system diseases, skeletal disorders, eye diseases, blood disorders, and complex developmental syndromes.

Many rare diseases are caused by a genetic alteration. As a result, diagnosing these conditions requires a combination of extensive clinical experience and advanced molecular tools. Physicians evaluate the medical signs and symptoms, family history, and patterns of inheritance, and integrate this information with genetic testing, gene sequencing, exome or genome sequencing, and comparisons with international databases. This makes it possible to identify similar cases around the world, gain a better understanding of the significance of a genetic finding, and move closer to a more accurate diagnosis.

Clinical Genetics and Personalized Medicine

In personalized medicine, which aims to tailor monitoring and treatment to each patient's unique biological profile, clinical genetics plays a critical role. When a rare disease is suspected, the central challenge is to decipher the underlying biological mechanism. By connecting genetic information with a patient's clinical findings, physicians can identify the specific disruption and translate it into clinical insights of tremendous value for the family: how the disease may progress, which specific tests and follow-up care are required, which family members may be at risk, and how to plan for the future with greater confidence.

The rapid advancement of sequencing technologies and computational biology tools has transformed a process that once required years of investigation into one that is more accurate and faster than ever before. In some cases, a genetic diagnosis may even open the door to a personalized treatment approach that targets the biological mechanism responsible for the disease.

What Do We Study at the Dangoor Center at Bar-Ilan University?

In the Dangoor Center's research laboratories, scientists work to bridge the gap between basic science and the real clinical needs encountered in practice. The center's researchers lead a range of advanced studies aimed at uncovering the underlying mechanisms of rare diseases and developing solutions for them: reaching a diagnosis, understanding its implications for patients and their families, and enabling more personalized monitoring and treatment.

Genetic Editing for Immune System Disorders: A groundbreaking study led by Dr. Ayal Hendel focuses on Severe Combined Immunodeficiency (SCID), commonly known as "bubble boy disease," a group of severe genetic disorders that impair the development of T cells in the immune system. In collaboration with researchers and physicians from Sheba Medical Center and Tel Aviv University, Dr. Hendel's laboratory developed an innovative strategy to correct the genetic defect using CRISPR gene-editing technology. This research demonstrates how understanding the cause of a monogenic disease, one that results from a change in a single gene, can serve as a direct foundation for developing corrective medical treatments in the future.

Studying Cellular Organelles and Their Function: Another research direction is led by Dr. Einat Zalckvar, whose work focuses on the peroxisome, a vital cellular organelle responsible for critical metabolic processes in the body. Impairment of this organelle can lead to severe rare genetic disorders that directly affect the brain, the nervous system, and the function of other essential body systems. Understanding the mechanisms that regulate and govern the activity of this organelle helps identify new potential targets for therapeutic intervention.

Population-Specific Clinical Genetics: Alongside research into cellular mechanisms, Bar-Ilan researchers are working to characterize the genetic landscape of Israel's diverse populations. Professor Tzipora Falik-Zaccai, a specialist in pediatrics and medical genetics, studies rare genetic diseases and develops genetic counseling services that are tailored both personally and culturally to population groups at increased risk for inherited disorders.

Multidisciplinary Collaboration: Connecting Patients, Physicians, and Researchers

One of the central challenges in the field of rare diseases is the fragmentation of knowledge. Because each disease affects only a small number of patients, medical expertise is often dispersed among physicians, laboratories, and medical centers around the world. Meaningful progress therefore depends on breaking down barriers and fostering close collaboration among professionals across multiple disciplines.

The Dangoor Center operates precisely within this shared space, serving as a bridge between academic research and clinical practice. The center promotes close collaborations with Sheba Medical Center at Tel HaShomer, as well as with the Azrieli Faculty of Medicine in the Galilee, where an advanced research center for genetics and cancer has been established.

These multidisciplinary collaborations, combined with computational technologies, statistical models, and artificial intelligence tools, make it possible to aggregate data from different patients, compare findings across families in Israel and around the world, and identify hidden biological patterns. Research on rare diseases at the Dangoor Center demonstrates how broad collaboration can lead to faster, more accurate diagnoses and move us closer to an era of truly personalized medicine for every individual.