Introduction Just recently, the paper titled Loss of function of FAM177A1, a Golgi complex localized protein, causes a novel neurodevelopmental disorder, was published in Genetics in Medicine. This paper was the culmination of the Hawkins family's 15-year diagnostic odyssey and defined FAM177A1-related neurodevelopmental disorder as a new medical condition. The paper describes the symptoms and genetic findings of a handful of patients (Charlotte and Cooper are individuals A1 and A2 in the paper), along with the research on cells and zebrafish that begin to shed light on the function of the FAM177A1 gene in human health. A PDF of the publication can be found below.
This publication would not have happened without the leadership of Dr. Nicole Legro, MD, and Jennefer Kohler, Genetic Counselor at Stanford, in partnership with the Stanford Center for Undiagnosed Diseases and its many collaborators including Berrak Ugur, PhD. Lilianna Solnica-Krezel, PhD. and Jimann Shin, PhD. These brilliant clinicians and scientists continue to be valuable advisors to the FAM177A1 Research Fund.
The path to uncovering and understanding FAM177A1-related neurodevelopmental disorder has been one of determination, collaboration, and perseverance. In this guest post, Dr. Legro (pictured below) shares her six-year journey—from the initial introduction to the Hawkins family to publishing the first study on this rare genetic disorder. This inspiring narrative highlights the power of patient-centered science and the unwavering commitment to advancing knowledge for families seeking answers. 🌟
Guest Blog by Dr. Nicole Legro
The Journey to Publishing the First Study on FAM177A1-Associated Neurodevelopmental Disease: Six Years in the Making
The Journey Begins
In 2018, during my first year of medical school, I started a summer research project at Stanford’s Center for Undiagnosed Diseases that would shape the next six years of my life. I was introduced to Cooper and Charlotte Hawkins, two children newly diagnosed with a rare genetic disorder involving the FAM177A1 gene—a gene with almost no known function at the time. This marked the beginning of a long journey to understand and characterize this disorder, eventually leading to the publication of a groundbreaking paper.
Building Connections: Collaboration and Discovery
Throughout that summer, I combed through thousands of pages of medical records, lab results, and imaging studies, searching for distinctive features that might define this disorder. Cooper and Charlotte’s symptoms—severe developmental delays and intractable seizures—hinted that FAM177A1 played a critical role in neurodevelopment. As we delved deeper, we found that this gene was conserved across species, suggesting its importance in humans and many animal species.
Early sequencing didn’t reveal clear answers, but repeated analyses uncovered two deletions in the FAM177A1 gene, which were believed to render the gene nonfunctional. Around the same time, we learned of another affected family through a publication by Alazami et al., inspiring us to connect with other clinicians nationwide. Through these efforts, we identified two additional U.S. families with similar FAM177A1 variants, adding crucial data to our study.
Collaboration proved essential. At a conference, we connected with researchers at Washington University in St. Louis, who created a zebrafish model carrying the same FAM177A1 variant as Cooper and Charlotte. Building and characterizing this model took years, and just as we prepared to publish, the COVID-19 pandemic struck, disrupting research worldwide. Still, new opportunities emerged: Yale researcher Berrak Ugur joined our team and discovered that FAM177A1 localizes to the Golgi apparatus, a key organelle for cellular function.
Publishing During a Pandemic: Navigating Setbacks and Progress
Just as we prepared to submit our manuscript in 2021, a researcher in London contacted our group with the identification of the disorder in several more families, providing important data that helped paint a more complete picture of FAM177A1-associated neurodevelopmental disease. However, navigating the international IRB approval process to formally collaborate proved challenging, causing further delays.
We pressed on, determined to publish our findings and make a difference for FAM177A1-affected families needing answers. An official publication would validate this disorder as a legitimate diagnosis and promote its inclusion in clinical genetic testing panels, enabling more diagnoses in the future.
Overcoming Challenges: The Road to Publication
The road to publication was challenging. Genetics in Medicine requested major revisions, and for more than a year, we submitted six rounds of edits. Balancing these demands with my 80-hour weeks as an OB/GYN resident was tough, but I wasn’t alone in the struggle. My co-first author, Jennefer Kohler, was juggling the birth of her baby while contributing to this project. Late nights, hundreds of emails, and research meetings with over 30 co-authors defined the final leg of this journey.
Moreover, the revisions were extensive and required collecting new data. Yet, the unwavering support of Cooper and Charlotte’s parents, Jill and Doug Hawkins, kept us going. Their dedication to their children and this research constantly reminded us of the importance of patient-centered science.
A Triumph: Seeing the Publication Go Live
Finally, in May 2024, after six years of hard work, our manuscript went live on PubMed. When I saw it published, tears filled my eyes. It was a moment of pride and relief and made the hours of work invested in this project worthwhile.
This project was a labor of love, driven by the desire to make a difference for families like the Hawkins. It taught me the value of perseverance, collaboration, and the importance of never giving up. I hope that this publication will lead to earlier diagnoses for families searching for answers and help more clinicians recognize FAM177A1-related neurodevelopmental disease.
To anyone who finds themselves undertaking a large project and wondering if it will manifest in the face of challenges—never, ever give up.
Dr. Legro's Groundbreaking Publication defining FAM177A1-related neurodevelopmental disorder as a new clinical entity.
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