Uncombable Hair Syndrome Genes Identified
By Michal Siman-Tov Posted on 29 Nov 2016 |
Image: A girl with uncombable hair syndrome (Photo courtesy of the University of Bonn).
Some children suffer from tangled hair that cannot be combed due to having the rare uncombable hair syndrome (UHS). Scientists have discovered that mutations in three genes encoding proteins involved in hair shaft formation lead to UHS, in Germany commonly known as Struwwelpeter Syndrome, named after a children’s storybook character.
Researchers from eight countries were involved in the study, led by the groups at University of Bonn (Bonn, Germany) and University of Toulouse (Toulouse, France).
Many parents know it is not always easy to comb children’s hair, yet with patience and nerves of steel the knots can usually be undone. In the case of UHS, brushes and combs are ineffective. Those affected have extremely frizzy, dry, generally light blonde hair with a characteristic shine, and resists attempts to tame it. These symptoms are most pronounced in childhood and then ease over time. In adulthood, the hair can more or less be styled normally.
Almost nothing has been known about the causes, particularly because the phenomenon is rare. It was described in the specialist literature for the first time in 1973; since then, around 100 cases have been documented worldwide. “However, we assume that there are much more people affected,” said Regina Betz, professor at University of Bonn, and a specialist for rare hereditary hair disorders, “Those who suffer from UHS do not necessarily seek help for this from a doctor or hospital.” It is known that the anomaly occurs more frequently in some families and thus appears to have genetic causes. “Via contact with colleagues from around the world, we managed to find 9 further children,” she said.
The scientists at Bonn sequenced all the genes of those affected, and found mutations in 3 genes involved in hair shaft formation. Two genes, PADI3 and TGM3, encode enzymes, while the third, TCHH, encodes a structural protein. In healthy hair, TCHH proteins are joined by crosslinking with very fine strands of keratin, which are responsible for hair shape and structure. During this process “PADI3 changes the hair shaft protein TCHH in such a way that the keratin filaments can adhere to it,” explained lead author Dr. Fitnat Buket Basmanav Ünalan, “The TGM3 enzyme then produces the actual link.”
Together with their University of Toulouse colleagues, the scientists at Bonn performed cell culture experiments that showed that loss-of-function mutations in any one of the three genes has fundamental effects on the structure and stability of the hair. Mice with defective PADI3 or TGM3 developed characteristic fur anomalies that were very similar to the human UHS phenotype.
“From the mutations found, a huge amount can be learned about the mechanisms involved in forming healthy hair, and why disorders sometimes occur,” said Prof. Betz, “At the same time, we can now secure the clinical diagnosis of ‘uncombable hair’ with molecular genetic methods.” Some hair anomalies are associated with severe concomitant diseases, which sometimes only become manifest in later life. However, UHS generally occurs in isolation, without other health impairments, so diagnosis can help reduce concerns about future illness. Uncombable hair may be tiresome and may also cause mental stress, said Prof. Betz, “However, those affected have no need to otherwise worry.”
The study, by Basmanav FBU et al, was published November 17, 2016, in the American Journal of Human Genetics.
Related Links:
University of Bonn
University of Toulouse
Researchers from eight countries were involved in the study, led by the groups at University of Bonn (Bonn, Germany) and University of Toulouse (Toulouse, France).
Many parents know it is not always easy to comb children’s hair, yet with patience and nerves of steel the knots can usually be undone. In the case of UHS, brushes and combs are ineffective. Those affected have extremely frizzy, dry, generally light blonde hair with a characteristic shine, and resists attempts to tame it. These symptoms are most pronounced in childhood and then ease over time. In adulthood, the hair can more or less be styled normally.
Almost nothing has been known about the causes, particularly because the phenomenon is rare. It was described in the specialist literature for the first time in 1973; since then, around 100 cases have been documented worldwide. “However, we assume that there are much more people affected,” said Regina Betz, professor at University of Bonn, and a specialist for rare hereditary hair disorders, “Those who suffer from UHS do not necessarily seek help for this from a doctor or hospital.” It is known that the anomaly occurs more frequently in some families and thus appears to have genetic causes. “Via contact with colleagues from around the world, we managed to find 9 further children,” she said.
The scientists at Bonn sequenced all the genes of those affected, and found mutations in 3 genes involved in hair shaft formation. Two genes, PADI3 and TGM3, encode enzymes, while the third, TCHH, encodes a structural protein. In healthy hair, TCHH proteins are joined by crosslinking with very fine strands of keratin, which are responsible for hair shape and structure. During this process “PADI3 changes the hair shaft protein TCHH in such a way that the keratin filaments can adhere to it,” explained lead author Dr. Fitnat Buket Basmanav Ünalan, “The TGM3 enzyme then produces the actual link.”
Together with their University of Toulouse colleagues, the scientists at Bonn performed cell culture experiments that showed that loss-of-function mutations in any one of the three genes has fundamental effects on the structure and stability of the hair. Mice with defective PADI3 or TGM3 developed characteristic fur anomalies that were very similar to the human UHS phenotype.
“From the mutations found, a huge amount can be learned about the mechanisms involved in forming healthy hair, and why disorders sometimes occur,” said Prof. Betz, “At the same time, we can now secure the clinical diagnosis of ‘uncombable hair’ with molecular genetic methods.” Some hair anomalies are associated with severe concomitant diseases, which sometimes only become manifest in later life. However, UHS generally occurs in isolation, without other health impairments, so diagnosis can help reduce concerns about future illness. Uncombable hair may be tiresome and may also cause mental stress, said Prof. Betz, “However, those affected have no need to otherwise worry.”
The study, by Basmanav FBU et al, was published November 17, 2016, in the American Journal of Human Genetics.
Related Links:
University of Bonn
University of Toulouse
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