GRN gene: When genetic information upends life

Rosa Rivoira was 25 and her sister Carmen was 29 when they received the diagnosis that their mother, the Argentine architect and visual artist Eugenia Streb, had frontotemporal dementia. Shortly after, they learned the results of their own genetic testing. “We are carriers of the mutant gene — that is, we tested positive, but it brought us nothing positive. At that moment we thought: now what do we do with this information?” Rosa said one afternoon in April 2026 at her parents’ home in Palermo Viejo.

The gene Rosa was talking about to is GRN — the one she and her sister inherited from their mother, whom everyone calls Genia because of her Polish roots. Some of Genia’s siblings — who have also been tested — carry the same pathogenic familial variant of GRN, while others do not. Because this mutation follows an autosomal dominant inheritance pattern, each child of a carrier has a 50% chance of inheriting the gene, and consequently a high risk of developing the disease, explains Nahuel Magrath, a neuropsychiatrist and director of the Fleni Frontotemporal Dementia Clinic, who has been supporting the Rivoira family since the diagnosis.

Genes are like instruction manuals that tell cells what to do. Your potential longevity could be written in your genes, according to a study published this year in Science. GRN, located on the long arm of chromosome 17, is not an ordinary gene. Among the roughly 20,000 that make up the human genome, GRN is responsible for producing progranulin, a protein crucial for healthy brain cell function. Inheriting a mutation in this gene can halve progranulin production or eliminate it entirely.

That lack of protein is what leads to frontotemporal dementia (FTD), a group of diseases that affect the frontal and temporal lobes of the brain — which control impulse regulation, movement, personality, language and empathy. In practice, this can translate into behaviors like running red lights, forgetting to pay bills, undressing in public or rifling through trash bins for sugary drink leftovers. The brain — weighing about 1,500 grams, with some 89 billion neurons forming interlinked structures, governing the essence and identity of each person and one organ we rarely think about — is one of the most complex things in the universe.

FTD is not easy to diagnose, nor does it have a cure or established treatments. There are no miracles. And most disturbing is that the odds of family members developing it in adulthood are almost inevitable. According to Jennifer Yokoyama, a neurogeneticist at the Fein Memory and Aging Center at the University of California, San Francisco, “pathogenic variants of the GRN gene account for roughly 5% of all frontotemporal dementia (FTD) cases and about 20% of FTD cases with a family history.”

“I think we really want to talk about this,” says Carmen Rivoira. “In the same three-month period we were given mom’s diagnosis, they did genetic studies on us. It was all driven by Alector’s protocol and if we were undergoing something, then it was of interest to know.”

Alector was a phase 3 trial that tested the efficacy of the drug latozinemab to slow disease progression in people with GRN mutation–related frontotemporal dementia, Magrath explains. Genia was the only participant from Latin America. However, the drug failed to meet its primary endpoint, and the trial was discontinued.

Based on what is happening to their mother, Rosa and Carmen estimate they have at least 35 years left before symptoms might begin. But there are no certainties. “This is an unknown we will unfortunately live with for the rest of our lives,” Rosa says, adding that both she and her sister will have to contend with questions about motherhood — whether to risk having a child who carries the mutation or to pursue preimplantation genetic diagnosis.

The real burden lies in what goes unsaid. In what Genia cannot express — she began showing the first symptoms of FTD seemingly overnight, forgetting pots on the stove, getting lost, having a car crash that left them shaken, then experiencing confusion and hallucinations involving colossal insects. Not long before her behavior changed, Genia was reading El peligro de estar cuerda (The danger of being sane) by Rosa Montero while spending long solitary hours creating art and exhibiting in museums, public spaces and galleries.

At one stage of the illness, the family thought it was good that Genia remained an artist, but over time they noticed that after the onset of FTD what she felt as an artist was mostly frustration. She began drawing on the tablecloth and then moved on to paper. Unlike those exceptional cases in which patients with dementia become artists, Genia’s case was the reverse. One of the messages she managed to convey when she could still write was “I don’t know how to do it.”

Ever since the disease began, she never again placed her subject in the center of the page, a change that piqued the interest of specialists such as Argentine neurologist and researcher Carolina Ardohain, who is part of Magrath’s team at Fleni. However, Ardohain suggested that although Genia’s drawings showed a marked tendency to depict mainly the contours or outer boundaries of figures, she did not consider this finding sufficient to infer the presence of any specific neurological syndrome.

After investigating Genia’s family tree and her Basque maternal surnames — Mugarza Bidegain — everything pointed to the Mugarza lineage as the origin of the FTD. Even then, Genia’s grandfather displayed apathetic behavior, what people at the time described as being “spaced out,” and it was attributed to arteriosclerosis. Back then, no one spoke of dementia.

Neurologist Fermín Moreno, from the Cognitive Decline Unit at Donostia University Hospital (HUD) in San Sebastián, in Spain’s Basque Country, has followed 18 families in Gipuzkoa province identified as carriers of the mutation internationally known as the Basque mutation of frontotemporal dementia.

According to the study by Moreno and his colleagues, their investigations led them to a group of families sharing a progranulin gene mutation linked to frontotemporal dementia that had not been described anywhere else in the world until then. “The Basque Country is not considered a genetically isolated population as such, but it is a population that has been fairly endogamous. For a time there was little genetic exchange with other populations, and that causes some specific mutations to be passed down through generations,” Moreno explains from a café in central San Sebastián.

Regarding the fact that there are families who share the Basque mutation without being directly related, Moreno clarifies: “In reality, yes — they probably come from what is called a common ancestor, a person centuries ago in whom the mutation occurred, and that has been passed from family to family. In other words, these apparently separate families likely originate from the same lineage.”

Although for the Rivoira sisters knowing they are carriers of the mutation feels like a hole in their chest, their attention today is focused on caring for their mother. Life inside the Casa Larga — as its owners call the house that was once a neighborhood merchandise warehouse with a concrete structure — has changed. The effort to maintain routines is an ever greater challenge. For that, specialized caregivers such as Naara Orueta, who accompanies Genia, make care easier by using her strong arms to transfer her from her wheelchair to the bathroom or bed while the family discovers what soothes her, what reduces her stress and what brings her pleasure.

Today the house still preserves two very tall poplars the couple planted when they bought the property, childhood portraits, children’s drawings, a photograph of the happy couple at the start of their relationship in 1989, and books from a life built with love and shared reading. In every corner, one can feel the strength of a united family, carried along by the fleeting nature of joy.

“Even with everything the doctors tried to do for us, there are ideas that are always uncomfortable and painful,” Carmen says on a windy Sunday. “At the time, there were many things we had to digest. An episode opened in which we had to deal with grief while at the same time receiving information about ourselves. It paralyzed me. And the idea of the future became strange. Being a woman in your thirties is not a trivial thing in this world. Now add the genetic element.”

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