Identification of a novel mutation in the KITLG gene in a Chinese family with familial progressive hyper- and hypopigmentation
| Autor: | Min Li, Jingliu Liu, Naihui Zhou, Miao Sun, Ziliang Yang, Xueli Li, Shoumin Zhang, Zhenlu Li, Jianbo Wang, Weisheng Li |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Adult
0301 basic medicine China medicine.medical_specialty lcsh:Internal medicine lcsh:QH426-470 Mutant Familial progressive hyper- and hypopigmentation Biology 030207 dermatology & venereal diseases 03 medical and health sciences Exon 0302 clinical medicine Genetics medicine Humans Coding region lcsh:RC31-1245 Gene Genetics (clinical) Hypopigmentation Stem Cell Factor Human genetics lcsh:Genetics 030104 developmental biology Albinism Oculocutaneous KITLG Gene KITLG gene Mutation Medical genetics medicine.symptom VTNNV motif Research Article |
| Zdroj: | BMC Medical Genomics, Vol 14, Iss 1, Pp 1-7 (2021) BMC Medical Genomics |
| ISSN: | 1755-8794 |
| Popis: | BackgroundFamilial progressive hyper- and hypopigmentation (FPHH, MIM 145250) is a rare hereditary skin disorder that is predominantly characterized by progressive, diffuse, partly blotchy hyperpigmented lesions intermingled with scattered hypopigmented spots, lentigines and sometimes Cafe-au-lait spots (CALs). Heterozygous mutations of the KIT ligand (KITLG, MIM 184745) gene are responsible for FPHH. To date, only eightKITLGmutations have been reported to be associated with FPHH, and no clear genotype–phenotype correlations have been established. This study aimed to identify the causative mutations in theKITLGgene in two Chinese FPHH patients.MethodsDirect sequencing of the coding regions ofKITLGwas performed. Pathogenicity prediction was performed using bioinformatics tools, including SIFT, Polyphen2, and SWISS-MODEL, and the results were further evaluated according to the 2015 American College of Medical Genetics and Genomics (ACMG) guidelines.ResultsThe novel mutation c.104A > T (p.Asn35Ile) and the recurrent mutation c.101C > T (p.Thr34Ile) inKITLGwere identified. As shown using SIFT and Polyphen-2 software, both mutations identified in this study were predicted to be detrimental variations. Three-dimensional protein structure modeling indicated that the mutant KITLG proteins might affect the affinity of KITLG for its receptor, c-KIT. According to the 2015 ACMG guidelines, the novel mutation c.104A > T was ‘likely pathogenic’.ConclusionsTo date, most of the identifiedKITLGmutations have been clustered within the conserved VTNNV motif (amino acids 33–37) in exon 2. The known mutations are only involved in 33 V, 34 T, 36 N, and 37 V but not 35 N. We have now identified a novel mutation inKITLG, c.104A > T, that was first reported in FPHH within the conserved 35 N motif. These results strengthen our understanding of FPHH and expand the mutational spectrum of theKITLGgene. |
| Databáze: | OpenAIRE |
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