Basmanav, F. Buket, Cesarato, Nicole, Kumar, Sheetal ORCID: 0000-0002-5240-079X, Borisov, Oleg, Kokordelis, Pavlos, Ralser, Damian J., Wehner, Maria, Axt, Daisy, Xiong, Xing ORCID: 0000-0001-5728-150X, Thiele, Holger, Dolgin, Vadim, Gossmann, Yasmina, Fricker, Nadine, Dewenter, Malin Katharina, Weller, Karsten, Suri, Mohnish ORCID: 0000-0001-9037-701X, Reichenbach, Herbert, Oji, Vinzenz, Addor, Marie-Claude, Ramirez, Karla, Stewart, Helen, Bartels, Natalie Garcia, Weibel, Lisa, Wagner, Nicola, George, Susannah, Kilic, Arzu, Tantcheva-Poor, Iliana, Stewart, Alison, Dikow, Nicola, Blaumeiser, Bettina ORCID: 0000-0001-9993-7319, Medvecz, Marta, Blume-Peytavi, Ulrike, Farrant, Paul, Grimalt, Ramon, Bertok, Sara, Bradley, Lisa, Eskin-Schwartz, Marina, Birk, Ohad Samuel, Bygum, Anette ORCID: 0000-0002-3004-0180, Simon, Michel ORCID: 0000-0003-3655-6329, Krawitz, Peter, Fischer, Christine, Hamm, Henning, Fritz, Gunter and Betz, Regina C. (2022). Assessment of the Genetic Spectrum of Uncombable Hair Syndrome in a Cohort of 107 Individuals. JAMA Dermatol., 158 (11). S. 1245 - 1254. CHICAGO: AMER MEDICAL ASSOC. ISSN 2168-6084

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Abstract

Importance Uncombable hair syndrome (UHS) is a rare hair shaft anomaly that manifests during infancy and is characterized by dry, frizzy, and wiry hair that cannot be combed flat. Only about 100 known cases have been reported so far. Objective To elucidate the genetic spectrum of UHS. Design, Setting, and Participants This cohort study includes 107 unrelated index patients with a suspected diagnosis of UHS and family members who were recruited worldwide from January 2013 to December 2021. Participants of all ages, races, and ethnicities were recruited at referral centers or were enrolled on their own initiative following personal contact with the authors. Genetic analyses were conducted in Germany from January 2014 to December 2021. Main Outcomes and Measures Clinical photographs, Sanger or whole-exome sequencing and array-based genotyping of DNA extracted from blood or saliva samples, and 3-dimensional protein modeling. Descriptive statistics, such as frequency counts, were used to describe the distribution of identified pathogenic variants and genotypes. Results The genetic characteristics of patients with UHS were established in 80 of 107 (74.8%) index patients (82 [76.6%] female) who carried biallelic pathogenic variants in PADI3, TGM3, or TCHH (ie, genes that encode functionally related hair shaft proteins). Molecular genetic findings from 11 of these 80 individuals were previously published. In 76 (71.0%) individuals, the UHS phenotype were associated with pathogenic variants in PADI3. The 2 most commonly observed PADI3 variants account for 73 (48.0%) and 57 (37.5%) of the 152 variant PADI3 alleles in total, respectively. Two individuals carried pathogenic variants in TGM3, and 2 others carried pathogenic variants in TCHH. Haplotype analyses suggested a founder effect for the 4 most commonly observed pathogenic variants in the PADI3 gene. Conclusions and Relevance This cohort study extends and gives an overview of the genetic variant spectrum of UHS based on molecular genetic analyses of the largest worldwide collective of affected individuals, to our knowledge. Formerly, a diagnosis of UHS could only be made by physical examination of the patient and confirmed by microscopical examination of the hair shaft. The discovery of pathogenic variants in PADI3, TCHH, and TGM3 may open a new avenue for clinicians and affected individuals by introducing molecular diagnostics for UHS.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Basmanav, F. BuketUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cesarato, NicoleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kumar, SheetalUNSPECIFIEDorcid.org/0000-0002-5240-079XUNSPECIFIED
Borisov, OlegUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kokordelis, PavlosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ralser, Damian J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wehner, MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Axt, DaisyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Xiong, XingUNSPECIFIEDorcid.org/0000-0001-5728-150XUNSPECIFIED
Thiele, HolgerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dolgin, VadimUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gossmann, YasminaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fricker, NadineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dewenter, Malin KatharinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weller, KarstenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Suri, MohnishUNSPECIFIEDorcid.org/0000-0001-9037-701XUNSPECIFIED
Reichenbach, HerbertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Oji, VinzenzUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Addor, Marie-ClaudeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ramirez, KarlaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stewart, HelenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bartels, Natalie GarciaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weibel, LisaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wagner, NicolaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
George, SusannahUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kilic, ArzuUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tantcheva-Poor, IlianaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stewart, AlisonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dikow, NicolaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Blaumeiser, BettinaUNSPECIFIEDorcid.org/0000-0001-9993-7319UNSPECIFIED
Medvecz, MartaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Blume-Peytavi, UlrikeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Farrant, PaulUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Grimalt, RamonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bertok, SaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bradley, LisaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eskin-Schwartz, MarinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Birk, Ohad SamuelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bygum, AnetteUNSPECIFIEDorcid.org/0000-0002-3004-0180UNSPECIFIED
Simon, MichelUNSPECIFIEDorcid.org/0000-0003-3655-6329UNSPECIFIED
Krawitz, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fischer, ChristineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hamm, HenningUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fritz, GunterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Betz, Regina C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-698471
DOI: 10.1001/jamadermatol.2022.2319
Journal or Publication Title: JAMA Dermatol.
Volume: 158
Number: 11
Page Range: S. 1245 - 1254
Date: 2022
Publisher: AMER MEDICAL ASSOC
Place of Publication: CHICAGO
ISSN: 2168-6084
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
TRICHOHYALIN; MICROSCOPYMultiple languages
DermatologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/69847

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