GRN Gene Mutation | Impact on Families & Brain Health

The Genetic Burden of Frontotemporal Dementia

Rosa and Carmen Rivoira were 25 and 29 years old when their mother, Argentine artist Eugenia Streb, received a diagnosis of frontotemporal dementia. Shortly after, the sisters learned they were carriers of the same pathogenic GRN gene mutation. This genetic variant, located on chromosome 17, prevents the production of progranulin, a protein essential for healthy brain cell function. Without it, neural pathways degrade, leading to the devastating cognitive and behavioral shifts characteristic of the disease.

Frontotemporal dementia affects the frontal and temporal lobes, which govern impulse control, personality, and empathy. Patients often experience radical changes in behavior, such as social withdrawal or impulsive actions. For the Rivoira family, the realization of their genetic status transformed their perspective on the future. They now live with the awareness that they carry a mutation that carries a 50 percent risk of manifesting in adulthood, a reality they must navigate while caring for their mother.

The Search for Medical Solutions

The family participated in a phase 3 clinical trial led by the biotechnology company Alector to test the drug latozinemab. The goal was to slow the progression of the disease in patients with the GRN mutation. Despite their hopes, the trial failed to meet its primary endpoint and was discontinued. Eugenia Streb remains one of the few individuals who underwent this experimental protocol in Latin America, highlighting the global reach of these trials.

Neurologist Fermín Moreno of Donostia University Hospital in Spain has spent years tracking similar cases in the Basque Country. He identified 18 families in Gipuzkoa province who share a specific progranulin gene mutation, often called the Basque mutation. Moreno notes that while the region is not strictly isolated, historical endogamy has allowed this mutation to persist across generations. He suggests that these families likely descend from a common ancestor who lived centuries ago.

Living with Uncertain Information

The impact of this diagnosis extends beyond physical care into the existential questions of daily life. The Rivoira sisters estimate they have roughly 35 years before potential symptom onset, yet they face the immediate challenge of caring for their mother. Their home in Palermo Viejo has become a place where they manage routines with the help of professional caregivers, even as they grapple with the emotional toll of witnessing their mother's decline.

Eugenia Streb, once a vibrant artist, lost her ability to create as the disease progressed. Her transition from painting to frustrated marks on paper serves as a silent marker of her condition. As the family continues to support her, they also confront personal decisions about the future, including whether to pursue preimplantation genetic diagnosis. The experience of the Rivoira family serves as a window into the difficult intersection of modern genetic knowledge and human endurance.