One gene, variants associated with many rare hair conditions

Researchers report that a gene and a disease-causing variant of this gene are responsible for most cases of UHS, a rare hair shaft abnormality that manifests during childhood.

Results from cohort study Posted in Gamma Dermatology It included 107 unrelated children and adults suspected of having UHS, as well as family members, all recruited from January 2013 to December 2021. Genetic analyzes were performed in Germany from January 2014 to December 2021 with exome sequencing.

The study builds on previous research

Senior author Regina C. Betz, MD, Professor of Skin Genetics at the Institute of Human Genetics, University Hospital Bonn, Bonn, Germany, told Medscape that in 2016, she and co-authors authored study On UHS Molecular Genetics. That study, in 18 people with UHS, identified variants in three genes — PADI3, TCHH and TGM3 — that encode proteins that play a role in hair shaft formation. The investigators described the deficiency in hair shaft formation and strengthening that occurs in the UHS phenotype, which is characterized by dry, curly, wired hair that cannot be combed flat.



Regina Betz

As a result of this previous work, “we base the assignment or confirmation of a clinical diagnosis of UHS on a molecular genetic diagnosis,” the authors wrote in the new study, rather than clinical appearance of hair and patient physical examination, with confirmation of hair shaft microscopy.

Social media as a tool for finding study participants

After a 2016 study, Betz and colleagues were contacted by several clinicians and the public through Facebook and other social media platforms with details about possible cases of UHS, an autosomal recessive disorder. Through these contacts, blood, saliva or DNA samples were sent to the investigators’ laboratory from 89 unrelated patients with an unrelated index (69 patients, 20 male patients) suspected of having UHS. The investigators wrote that this led to the identification of pathogenic variants in 69 cases.

“In the first study, we had 18 patients, and then we tried to collect as many as possible” to determine the main mechanism behind UHC, Betz said. One question, she noted, is whether there are additional genes responsible for UHS. “So far, we’re not sure, because 25% [of cases in the new study]We did not find any mutation in the three known genes.”

The current study resulted in the discovery of eight new pathogenic variants in PADI3, which are responsible for 71.0% (76) of the 107 cases. Of these, the investigators wrote, “6 were individual observations and 2 were observed in 3 and 2 individuals, respectively”.

Betz noted that children can outgrow the disorder, but it can continue into adulthood. She added that contacts made by investigators with parents of children with UHS revealed that these children are often the targets of bullying by other children.

She and her colleagues will continue this research and are currently studying adults with UHS.

Research leads to possible treatment pathways

Jeff Donovan, MD, FRCPC, FAAD, dermatologist and medical director of the Donovan Hair Clinic in Whistler, British Columbia, described these findings as fundamental to understanding UHS and establishing pathways for possible treatments.



Dr. Jeff Donovan

Donovan, who is also a clinical instructor in the department of dermatology at the University of British Columbia, Vancouver, and president of the Canadian Hair Loss Foundation, said the study “defines more about the genetic basis of this challenging condition.” “We really need this kind of information in order to get any kind of evidence as to how to deal with it,” he told Medscape.

“In the world of hair loss, it’s pretty clear that if you can understand the genetic basis of things, or the basic science of the condition, whether it’s basic genes or basic immunology, you give yourself the best chance of developing good treatments,” Donovan said.

The article provides advanced genetic information about the condition, so geneticists can test for at least three markers if they suspect UHS, Donovan noted.

The condition can lead to bullying

Donovan also commented that UHS can have a detrimental effect on children with regard to socializing with peers. “Having hair so full like this is a challenge because kids get annoyed,” he said.

“Parents are often the worst affected” when a child between the ages of 2 and 5 has a hair condition like UHS. But by ages 5 to 9, “children develop self-identity and an understanding of the different aspects of self-esteem and how they look and feel like others. This is where the annoyances really start. That’s where it gets annoying.”

Betz and Donovan have not disclosed any relevant financial relationships.

Gamma Dermatol. Posted online August 31, 2022. Summary

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