Study co-author Prof. Regina Betz, of the Institute for Human Genetics at the University of Bonn in Germany, and team recently published the details of their discovery in The American Journal of Human Genetics.

Uncombable hair syndrome (UHS) is a condition whereby the hair shaft - the part of the hair just above the scalp - is abnormally shaped, resulting in frizzy, dry, and disordered hair that cannot be controlled with brushing.

Also referred to as "spun-glass hair," UHS is a very rare disorder; to date, only 100 cases have been reported worldwide, though there are thought to be many more undiagnosed cases.

"Those who suffer from uncombable hair do not necessarily seek help for this from a doctor or hospital," notes Prof. Betz.

According to the National Center for Advancing Translational Sciences - a part of the National Institutes of Health - symptoms of UHS usually arise between the age of 3 months and 12 years. The condition normally improves or resolves with puberty onset, but it can persist into adulthood.

Since UHS was first described in the early 1970s, little information has been unearthed about what causes the condition, primarily because it is so rare, making it difficult to study.

However, it is believed that UHS has a genetic component, since hair shaft abnormalities are often found in relatives of individuals with the condition. These abnormalities may not always lead to UHS, though.
Mutations found in three genes linked to hair shaft formation

For the new study, Prof. Betz and team - with help from colleagues across the globe - managed to track down 11 children who had been diagnosed with UHS.

The researchers sequenced the genes of these children and compared them with large national databases, in order to identified any gene mutations that might be associated with UHS.

The team pinpointed mutations in three genes that are involved in hair shaft formation: PADI3, TGM3, and TCHH.

The researchers explain that in healthy hair, proteins in the TCHH gene are connected by very fine strands of keratin - a protein that maintains hair shape and structure.

"PADI3 changes the hair shaft protein TCHH in such a way that the keratin filaments can adhere to it," explains lead study author Dr. Fitnat Buket Basmanav Ünalan. "The TGM3 enzyme then produces the actual link."
Just one of the gene mutations can affect hair shape, structure

For the next part of the study, the researchers set out to determine how mutations in the three genes might impact hair formation through laboratory experiments with cell cultures and mouse models.

They found that abnormal functioning in just one of the three genes can have negative implications for hair shape and structure, and in mouse models, mutations in the PADI3 and TGM3 genes led to fur abnormalities comparable to hair abnormalities in people with UHS.

Overall, the researchers say their findings suggest a possible genetic cause for UHS, and they may also shed light on the mechanisms behind other hair-related disorders.

    "From the mutations found, a huge amount can be learned about the mechanisms involved in forming healthy hair, and why disorders sometimes occur. At the same time, we can now secure the clinical diagnosis of 'uncombable hair' with molecular genetic methods."

    Prof. Regina Betz