Undiagnosed Rare Disease Linked to PHETA1 Gene Variant


A 6-year-old girl presented with facial abnormalities, developmental delays, and issues with her renal system. Her family took her to their family physician. Then, when that uncovered no cause, they moved on to a specialist. But doctors remained vexed. Eventually, the girl’s case was identified by the NIH Undiagnosed Diseases Program. Genetic testing uncovered the cause: a mutated PHETA1 gene. Yet, intriguingly, the rare disease still remains undiagnosed and possibly never seen before.

You can read the full study results in Disease Models and Mechanisms.

The PHETA1 Gene

The PHETA1 gene plays a role in endocytic/endosomal trafficking. Not quite sure what that is? Basically, endocytic trafficking helps transport proteins on a cellular level. According to an explanation from Nature, this trafficking assists with:

nutrient uptake, cell adhesion and migration, receptor signaling, pathogen entry and cell polarity.

In other words, it helps maintain the health of the cells, signaling relating to immune responses, and specialized cell function.

The Study

Researchers wanted to understand how and why the mutated PHETA1 gene resulted in the observed symptoms. They used CRISPR, a gene-editing technology, to create zebrafish models with PHETA1 variants. Researchers discovered that the zebrafish models expressed excess OCRL protein, which help modify cell membranes and is associated with Lowe syndrome.

Lowe Syndrome

The patient did not receive a diagnosis of Lowe syndrome. However, her condition is similar. Lowe syndrome is a condition which affects the brain, eyes, and kidneys.

Symptoms include congenital cataracts and vision impairment, infantile glaucoma, developmental delays, intellectual impairments, problems with behavior, epilepsy, lack of motor skills, poor muscle tone, and renal (kidney) abnormalities. The renal issues make it difficult for patients to absorb proper nutrients. Learn more about Lowe syndrome here. 

PHETA1 and Zebrafish

The PHETA1 gene defects in zebrafish caused poor renal function and craniofacial development (the development of skull and face bones). Scientists found that these zebrafish had difficulty regulating cathepsin K, a protein that can break down collagen, gelatin, and elastin. Cathepsin K contributes to poor craniofacial development.

Now, scientists now have a starting point for future research. Moving forward, more research is needed on both PHETA1 mutations and on this specific patient’s condition. This will help develop targeted treatment options.

Read the original article here.

Jessica Lynn

Jessica Lynn

Jessica Lynn has an educational background in writing and marketing. She firmly believes in the power of writing in amplifying voices, and looks forward to doing so for the rare disease community.

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