Autosomal recessive hypotrichosis with loose anagen hairs associated with TKFC mutations*
| العنوان: | Autosomal recessive hypotrichosis with loose anagen hairs associated with TKFC mutations* |
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| المؤلفون: | Leslie Castelo-Soccio, Alicia Cabezas, João Meireles Ribeiro, Michael A. Simpson, Alan D. Irvine, Franca Fraternali, Alexandros Onoufriadis, María Jesús Costas, Maeve A. McAleer, Joseph Chi Fung Ng, José Carlos Cameselle, José Canales, John A. McGrath, Joaquim Rui Rodrigues |
| المصدر: | British Journal of Dermatology. 184:935-943 |
| بيانات النشر: | Oxford University Press (OUP), 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Mutation, Missense, Dermatology, Biology, Hypotrichosis, medicine.disease_cause, Compound heterozygosity, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Missense mutation, Kinase activity, Child, Mutation, integumentary system, Wild type, Alopecia, medicine.disease, Molecular biology, medicine.anatomical_structure, Scalp, Hair Diseases, Cyclase activity, Hair |
| الوصف: | Background Loose anagen hair is a rare form of impaired hair anchorage in which anagen hairs that lack inner and outer root sheaths can be gently and painlessly plucked from the scalp. This condition usually occurs in children and is often self-limiting. A genetic basis for the disorder has been suggested but not proven. A better understanding the aetiology of loose anagen hair may improve prevention and treatment strategies. Objectives To identify a possible genetic basis of loose anagen hair using next-generation DNA sequencing and functional analysis of variants identified. Methods In this case study, whole-exome sequencing analysis of a pedigree with one affected individual with features of loose anagen hair was performed. Results The patient was found to be compound heterozygous for two single-nucleotide substitutions in TKFC resulting in the following missense mutations: c.574G> C (p.Gly192Arg) and c.682C> T (p.Arg228Trp). Structural analysis of human TKFC showed that both mutations are located near the active site cavity. Kinetic assays of recombinant proteins bearing either of these amino acid substitutions showed almost no dihydroxyacetone kinase or D-glyceraldehyde kinase activity, and FMN cyclase activity reduced to just 10% of wildtype catalytic activity. Conclusions TKFC missense mutations may predispose to the development of loose anagen hairs. Identification of this new biochemical pathobiology expands the metabolic and genetic basis of hypotrichosis. |
| تدمد: | 1365-2133 0007-0963 |
| DOI: | 10.1111/bjd.19481 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d6405676ead94e05dcc29132db62dfbb https://doi.org/10.1111/bjd.19481 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d6405676ead94e05dcc29132db62dfbb |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 13652133 00070963 |
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| DOI: | 10.1111/bjd.19481 |