Laura Keehan, a third-year medical student at Baylor, has been passionate about working with people who have intellectual and developmental disabilities (IDD) for a long time.

Inspired by her two cousins who have Down syndrome and autism, she always knew she wanted to pursue a career helping people with IDD.

A lecture with Dr. Lorraine Potocki, professor of molecular and human genetics, during her first year of medical school convinced her that genetics was the way to go.

“I realized genetics perfectly combines my interest in clinical care, research, advocacy and teaching,” Keehan said. “I feel like I can do all the things I love in one field. In addition to providing clinical care for patients with intellectual and developmental disabilities, we do a lot of research because there’s still so much we don’t know. We have to advocate for our patients to get the best care. And we act as a teacher to our patients and families, explaining really complicated concepts and how it applies to them.”

Keehan joined the Genetics and Genomics Pathway (GGP), an enrichment program that runs concurrent with the medical school curriculum at Baylor. The GGP builds on the foundation of genetic principles provided to all Baylor students and offers additional opportunities for mentored research, clinical care, genetic laboratory interpretation and venues for patient education and advocacy.

A pre-clinical genetics elective with Dr. Lindsay Burrage, assistant professor of molecular and human genetics, led Keehan to join research with the Undiagnosed Diseases Network (UDN) during her first year of medical school. The UDN is an initiative funded by the National Institutes of Health that works to diagnose patients across the country who have not been able to find a diagnosis for their condition through regular clinical genetic testing. Baylor College of Medicine is a clinical site, sequencing core and model organism screening center for the UDN.

This month, Keehan had her first, first-author journal publication in the American Journal of Medical Genetics – Part A explaining how she and a team of Baylor researchers solved a UDN case. The paper describes the case of a 5-year-old boy who has a developmental disorder causing issues with his eyes and motor skills. Previous genetic testing did not reveal the genetic variant causing his symptoms.

After performing genome sequencing on the patient’s DNA, Keehan and the team led by Burrage found a variant on the gene ITPR1. Variants of this gene have been associated with Gillespie syndrome, which aligned with the patient’s symptoms, but the Baylor team needed to validate that this variant was in fact the cause of the patient’s genetic disorder. In the lab, Keehan and her fellow researchers examined how this variant would affect the protein structure and ultimately determined that it was the cause of the patient’s symptoms.

“This is the first patient with a de novo intronic variant—a non-inherited variant in the noncoding region of DNA—that has been shown to cause Gillespie syndrome,” Keehan said. “That variant changed the structure of the protein. It’s as if you added a bunch of letters in between paragraphs in a book. The story doesn’t make sense with those changes.”

“Laura fully integrated herself into our UDN sequence analysis team, and she identified this project as the one that she wanted to pursue during one of our monthly meetings. Her laboratory work investigating the consequences of this variant in ITPR1 provided a key piece of evidence that we needed to solve this case,” said Burrage, corresponding author of the study.

Her own family experience with people who have IDD helps her understand the importance of finding a genetic diagnosis for a patient, Keehan said.

“It can bring relief and closure to families who are often on a diagnostic journey for years,” Keehan said. “I know it provides solace to families to know that it’s a genetic condition and no one’s fault. It also can help guide patients through healthcare needs for the rest of their lives.”

This publication is something Keehan has been working toward since high school when she began lab research work. Now, she is already working on her next publication with the UDN.

“I am really excited to be able to do this research and write it up in a way that everyone else can read and understand,” Keehan said. “It’s like you’re telling your own story. Here was our problem, here’s what we did and here’s what we found.”

By Molly Chiu