Titre
Assessment of the Genetic Spectrum of Uncombable Hair Syndrome in a Cohort of 107 Individuals.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Basmanav, F.B.
Auteure/Auteur
Cesarato, N.
Auteure/Auteur
Kumar, S.
Auteure/Auteur
Borisov, O.
Auteure/Auteur
Kokordelis, P.
Auteure/Auteur
Ralser, D.J.
Auteure/Auteur
Wehner, M.
Auteure/Auteur
Axt, D.
Auteure/Auteur
Xiong, X.
Auteure/Auteur
Thiele, H.
Auteure/Auteur
Dolgin, V.
Auteure/Auteur
Gossmann, Y.
Auteure/Auteur
Fricker, N.
Auteure/Auteur
Dewenter, M.K.
Auteure/Auteur
Weller, K.
Auteure/Auteur
Suri, M.
Auteure/Auteur
Reichenbach, H.
Auteure/Auteur
Oji, V.
Auteure/Auteur
Addor, M.C.
Auteure/Auteur
Ramirez, K.
Auteure/Auteur
Stewart, H.
Auteure/Auteur
Garcia Bartels, N.
Auteure/Auteur
Weibel, L.
Auteure/Auteur
Wagner, N.
Auteure/Auteur
George, S.
Auteure/Auteur
Kilic, A.
Auteure/Auteur
Tantcheva-Poor, I.
Auteure/Auteur
Stewart, A.
Auteure/Auteur
Dikow, N.
Auteure/Auteur
Blaumeiser, B.
Auteure/Auteur
Medvecz, M.
Auteure/Auteur
Blume-Peytavi, U.
Auteure/Auteur
Farrant, P.
Auteure/Auteur
Grimalt, R.
Auteure/Auteur
Bertok, S.
Auteure/Auteur
Bradley, L.
Auteure/Auteur
Eskin-Schwartz, M.
Auteure/Auteur
Birk, O.S.
Auteure/Auteur
Bygum, A.
Auteure/Auteur
Simon, M.
Auteure/Auteur
Krawitz, P.
Auteure/Auteur
Fischer, C.
Auteure/Auteur
Hamm, H.
Auteure/Auteur
Fritz, G.
Auteure/Auteur
Betz, R.C.
Auteure/Auteur
Liens vers les unités
ISSN
2168-6084
Statut éditorial
Publié
Date de publication
2022-11-01
Volume
158
Numéro
11
Première page
1245
Dernière page/numéro d’article
1253
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Résumé
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.
To elucidate the genetic spectrum of UHS.
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.
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.
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.
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.
To elucidate the genetic spectrum of UHS.
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.
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.
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.
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.
PID Serval
serval:BIB_0293C98501B7
PMID
Date de création
2022-09-05T06:56:55.307Z
Date de création dans IRIS
2025-05-20T16:30:38Z