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The cause of uncombable hair syndrome identified

Surprised disheveled preschooler girl with long hair

In 1973, the rare syndrome of uncombable hair or ‘pili trianguli et canaliculi‘ was described by a Toulouse dermatologist. More than 40 years later, Michel Simon, Inserm research director his colleagues at the ‘Epidermal Differentiation and Rheumatoid Autoimmunity’ Unit [UDEAR] (Inserm/CNRS/Toulouse III – Paul Sabatier University) have identified its genetic cause. These results are published in The American Journal of Human Genetics.

Uncombable hair syndrome is a rare disease of the hair, the prevalence of which is unknown. It generally begins during childhood between 3 months and 12 years. Dry and unruly, the hair of affected children becomes gradually silver-blond or straw coloured. Hairs stand up on the scalp and grow in all directions. It is impossible to comb it or to flatten it with a comb. In detail, scanning electron microscopy reveals a longitudinal groove running their entire length, with a triangular or kidney-shaped cross-section. However, this syndrome is not disabling and undergoes spontaneous at the end of childhood.



he researchers, working with a team from the Human Genetics Institute at Bonn University and dermatologists or geneticists from 7 different countries, have discovered that the disease is due to recessive mutations of a trio of genes that contribute to forming the hair: the gene coding for one of its structural components, trichohyalin (TCHH); or two genes coding for enzymes that take it in turns as target: peptidyl-arginine deiminase 3 (Pad3) and transglutaminase 3 (TGase3).

Furthermore, the researchers have also shown, in mice, that inactivating the Pad3 gene alters the shape of the fur and whiskers of animals, as had already been reported in TGase3-deficient mice.

In conclusion, the absence of TCHH or failure of the biochemical cascade that results in stiffening the hair stem are responsible for the hair formation abnormalities characteristic of uncombable hair syndrome or ‘pili trianguli et canaliculi‘.

These results, as well as describing the molecular cause of the disease and enabling better diagnosis, provide knew knowledge about the hair and the mechanisms of its formation£ concludes Michel Simon, Inserm research director.

For further information

Although extremely rare, the syndrome has long been known. It was brought to public awareness by the famous literary figure ‘Struwwelpeter’ created by children’s author Heinrich Hoffmann in 1845. The book was subsequently translated into English by Mark Twain as ‘Slovenly Peter’. Although he never said so, one might even think that it inspired director Tim Burton to make his film Edward Scissorhands.

Researcher Contact
Michel Simon Directeur de recherche Inserm Unité "Différenciation épithéliale et autoimmunité rhumatoïde" UDEAR (Inserm/CNRS/ Université Toulouse III - Paul Sabatier) +33 5 61 15 84 27 rf.mresni@nomis.lehcim
Press Contact
Juliette Hardy rf.mresni@esserp
Mutations in Three Genes Encoding Proteins Involved in Hair Shaft Formation Cause Uncombable Hair Syndrome Buket Ü. Basmanav,1,2,3 Laura Cau,4,23 Aylar Tafazzoli,1,23 Marie-Claire Méchin,4,23 Sabrina Wolf,1 Maria Teresa Romano,1 Frederic Valentin,5 Henning Wiegmann,5 Anne Huchenq,4 Rima Kandil,1 Natalie Garcia Bartels,6 Arzu Kilic,7 Susannah George,8 Damian J. Ralser,1 Stefan Bergner,1 David J.P. Ferguson,9 Ana-Maria Oprisoreanu,10 Maria Wehner,1 Holger Thiele,11 Janine Altmüller,11,12 Peter Nürnberg,11,13,14 Daniel Swan,15 Darren Houniet,15 Aline Büchner,16 Lisa Weibel,16,17 Nicola Wagner,18 Ramon Grimalt,19 Anette Bygum,20 Guy Serre,4 Ulrike Blume-Peytavi,6 Eli Sprecher,21 Susanne Schoch,10 Vinzenz Oji,5 Henning Hamm,22 Paul Farrant,8 Michel Simon,4,23 and Regina C. Betz1,23,* 1 Institute of Human Genetics, University of Bonn, 53127 Bonn, Germany; 2 Department of Neuro- and Sensory Physiology, University Medical Center Göttingen, 37073 Göttingen, Germany; 3 Campus Laboratory for Advanced Imaging, Microscopy and Spectroscopy, University of Göttingen, 37073 Göttingen, Germany; 4 CNRS UMR5165 and INSERM U1056 and University of Toulouse, 31059 Toulouse, France; 5 Department of Dermatology, University of Münster, 48149 Münster, Germany; 6 Clinical Research Center for Hair and Skin Science, Department of Dermatology and Allergy, Charité-Universitätsmedizin Berlin, Berlin 10117, Germany; 7 Dermatology Department, Balikesir University School of Medicine, 10100 Balikesir, Turkey; 8 Dermatology Department, Brighton and Sussex University Hospitals NHS Trust, Brighton General Hospital, Elm Grove, Brighton BN2 3EW, UK; 9 Nuffield Department of Clinical Laboratory Science, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK; 10 Department of Neuropathology and Department of Epileptology, University of Bonn, 53127 Bonn, Germany; 11 Cologne Center for Genomics, University of Cologne, 50931 Cologne, Germany; 12 Institute of Human Genetics, University of Cologne, 50931 Cologne, Germany; 13 Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany; 14 Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, 50931 Cologne, Germany; 15 Computational Biology Group, Oxford Gene Technology, Oxford OX5 1PF, UK; 16 Pediatric Dermatology Department, University Children’s Hospital Zurich, University Hospital of Zurich, 8032 Zurich, Switzerland; 17 Dermatology Department, University Hospital Zurich, 8032 Zurich, Switzerland; 18 Clinical Center Darmstadt, 64297 Darmstadt, Germany; 19 Universitat Internacional de Catalunya, Sant Cugat del Vallès, 08195 Barcelona, Spain; 20 Department of Dermatology and Allergy Centre, Odense University Hospital, 5000 Odense, Denmark; 21 Department of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv 64239, Israel; 22 Department of Dermatology, Venereology, and Allergology, University Hospital Würzburg, 97080 Würzburg, Germany 23 These authors contributed equally to this work   The American Journal of Human Genetics, novembre 2016 DOI: 10.1016/j.ajhg.2016.10.004