Unlocking the Genetics Behind a Rare Lung Disease

Dr Carolina Jaramillo Oquendo specialises in understanding the genetics behind Primary Cilia Dyskinesia (PCD), a rare inherited disorder that affects the tiny hair‑like structures, or motile cilia, that keep our airways clear.

Her work aims to improve diagnosis for patients with rare diseases by using cutting ‑ edge sequencing technologies to identify mutations that standard clinical testing often misses.

A Passion for Genetics

Carolina’s interest in genetics was sparked during her undergraduate studies in biological engineering.

“As part of a module on genetics and cell cultures, we were able to look at our own DNA and see our chromosomes under a microscope,” she recalls. “Genetics has fascinated me ever since.”

That passion led her to a PhD in cancer genetics and human genomics at the University of Southampton.

“In cancer genetics, you can do incredible molecular work, but it’s sometimes difficult to see how that translates for individual patients,” Carolina explains. “Working in diagnostics has given me the balance I was looking for: cutting ‑ edge research alongside tangible clinical impact. ”

Understanding Primary Ciliary Dyskinesia (PCD)

PCD is a recessive genetic disorder. When the motile cilia lining the lungs, nose and upper respiratory tract do not function properly, patients face chronic congestion, recurrent infections, breathing difficulties and long ‑ term respiratory complications.

The condition has similarities to cystic fibrosis, but is much rarer – and that rarity creates barriers for both diagnosis and research.

Closing the Diagnostic Gap

Because PCD is so uncommon, patient numbers are small and many cases go undiagnosed.

“With rare conditions, only around 30% of patients receive a molecular diagnosis,” Carolina explains. “For the other 70%, we still don’t know what genetic change is causing their condition.”

A major reason lies in how current NHS sequencing works. Standard tests examine only the protein ‑ coding regions of known genes, leaving large portions of DNA unexplored.

“The bits of DNA that don’t code for proteins often get missed,” says Carolina says. “But those regions can have a huge impact, especially on how genes are spliced and processed.”

Carolina’s earlier research focused on these overlooked non ‑ coding regions, using RNA sequencing to reveal changes invisible at the DNA level. Now, as part of the Southampton PCD team, she takes on the most complex diagnostic puzzles: cases with only one identified variant in a recessive condition, or cases where clinicians feel certain of a PCD diagnosis but no mutation can be found.

“We use short ‑ read RNA sequencing to see whether variants are affecting gene splicing, ” she explains. “ And I ’ ve recently received funding to explore long ‑ read RNA sequencing , the next generation of technology. The goal is to increase diagnostic rates even further. ”

Why Diagnosis Matters

At University Hospital Southampton, patients with a clinical diagnosis of PCD can already access treatments. But identifying the exact gene mutation opens doors to far more personalised care.

“If we know the specific gene, we can begin developing targeted therapies or gene ‑ based treatments, ” Carolina says. “ It ’ s similar to cystic fibrosis, where certain mutations now have tailored therapies. For PCD, we ’ re only just getting started, but understanding the genetics is the first step. ”

A confirmed molecular diagnosis also helps clinicians predict prognosis and understand whether certain gene variants cause more severe disease.

“The diagnosis is the foundation,” Carolina explains. “It allows us to understand progression, develop therapies and give families clearer answers.”

The impact extends beyond respiratory disease. The same sequencing technologies have helped identify inherited cancer variants – information that can shape how families are monitored and treated.

“That’s what I really enjoy about my work,” Carolina reflects. “I get to be the link: doing something scientifically new and exciting while seeing the clinical impact directly.”