Basmanav, F. Buket U., Cau, Laura ORCID: 0000-0002-2480-536X, Tafazzoli, Aylar, Mechin, Marie-Claire, Wolf, Sabrina, Romano, Maria Teresa, Valentin, Frederic, Wiegmann, Henning, Huchenq, Anne, Kandil, Rima, Bartels, Natalie Garcia, Kilic, Arzu, George, Susannah, Ralser, Damian J., Bergner, Stefan, Ferguson, David J. P., Oprisoreanu, Ana-Maria ORCID: 0000-0002-9409-0830, Wehner, Maria, Thiele, Holger, Altmueller, Janine, Nuerenberg, Peter, Swan, Daniel ORCID: 0000-0001-8978-8129, Houniet, Darren, Buechner, Aline, Weibel, Lisa, Wagner, Nicola, Grimalt, Ramon, Bygum, Anette ORCID: 0000-0002-3004-0180, Serre, Guy, Blume-Peytavi, Ulrike, Sprecher, Eli, Schoch, Susanne, Oji, Vinzenz ORCID: 0000-0003-1380-4828, Hamm, Henning, Farrant, Paul, Simon, Michel ORCID: 0000-0003-3655-6329 and Betz, Regina C. (2016). Mutations in Three Genes Encoding Proteins Involved in Hair Shaft Formation Cause Uncombable Hair Syndrome. Am. J. Hum. Genet., 99 (6). S. 1292 - 1305. CAMBRIDGE: CELL PRESS. ISSN 1537-6605

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Abstract

Uncombable hair syndrome (UHS), also known as spun glass hair syndrome,'' pili trianguli et canaliculi,'' or cheveux incoiffables'' is a rare anomaly of the hair shaft that occurs in children and improves with age. UHS is characterized by dry, frizzy, spangly, and often fair hair that is resistant to being combed flat. Until now, both simplex and familial UHS-affected case subjects with autosomal-dominant as well as - recessive inheritance have been reported. However, none of these case subjects were linked to a molecular genetic cause. Here, we report the identification of UHS-causative mutations located in the three genes PADI3 (peptidylarginine deiminase 3), TGM3 (transglutaminase 3), and TCHH (trichohyalin) in a total of 11 children. All of these individuals carry homozygous or compound heterozygous mutations in one of these three genes, indicating an autosomal-recessive inheritance pattern in the majority of UHS case subjects. The two enzymes PADI3 and TGM3, responsible for posttranslational protein modifications, and their target structural protein TCHH are all involved in hair shaft formation. Elucidation of the molecular outcomes of the disease-causing mutations by cell culture experiments and tridimensional protein models demonstrated clear differences in the structural organization and activity of mutant and wildtype proteins. Scanning electron microscopy observations revealed morphological alterations in hair coat of Padi3 knockout mice. All together, these findings elucidate the molecular genetic causes of UHS and shed light on its pathophysiology and hair physiology in general.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Basmanav, F. Buket U.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cau, LauraUNSPECIFIEDorcid.org/0000-0002-2480-536XUNSPECIFIED
Tafazzoli, AylarUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mechin, Marie-ClaireUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wolf, SabrinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Romano, Maria TeresaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Valentin, FredericUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wiegmann, HenningUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Huchenq, AnneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kandil, RimaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bartels, Natalie GarciaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kilic, ArzuUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
George, SusannahUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ralser, Damian J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bergner, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ferguson, David J. P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Oprisoreanu, Ana-MariaUNSPECIFIEDorcid.org/0000-0002-9409-0830UNSPECIFIED
Wehner, MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thiele, HolgerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Altmueller, JanineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nuerenberg, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Swan, DanielUNSPECIFIEDorcid.org/0000-0001-8978-8129UNSPECIFIED
Houniet, DarrenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Buechner, AlineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weibel, LisaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wagner, NicolaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Grimalt, RamonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bygum, AnetteUNSPECIFIEDorcid.org/0000-0002-3004-0180UNSPECIFIED
Serre, GuyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Blume-Peytavi, UlrikeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sprecher, EliUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schoch, SusanneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Oji, VinzenzUNSPECIFIEDorcid.org/0000-0003-1380-4828UNSPECIFIED
Hamm, HenningUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Farrant, PaulUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Simon, MichelUNSPECIFIEDorcid.org/0000-0003-3655-6329UNSPECIFIED
Betz, Regina C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-254619
DOI: 10.1016/j.ajhg.2016.10.004
Journal or Publication Title: Am. J. Hum. Genet.
Volume: 99
Number: 6
Page Range: S. 1292 - 1305
Date: 2016
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 1537-6605
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
SCANNING-ELECTRON-MICROSCOPY; PEPTIDYLARGININE DEIMINASES; ECTODERMAL DYSPLASIA; DOMINANT INHERITANCE; CHEVEUX INCOIFFABLES; PILI-TRIANGULI; ET-CANALICULI; AUTOANTIBODIES; SKIN; TRICHOHYALINMultiple languages
Genetics & HeredityMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/25461

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