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Identification of a novel mutation in the KITLG gene in a Chinese family with familial progressive hyper- and hypopigmentation.
BMC Med Genomics. 2021 01 06; 14(1):12.BM

Abstract

BACKGROUND

Familial 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 eight KITLG mutations 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 the KITLG gene in two Chinese FPHH patients.

METHODS

Direct sequencing of the coding regions of KITLG was 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.

RESULTS

The novel mutation c.104A > T (p.Asn35Ile) and the recurrent mutation c.101C > T (p.Thr34Ile) in KITLG were 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'.

CONCLUSIONS

To date, most of the identified KITLG mutations 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 in KITLG, 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 the KITLG gene.

Authors+Show Affiliations

Department of Dermatology, Henan Provincial People's Hospital, Henan University People's Hospital, Zhengzhou, 450003, China.Institute for Fetology, The First Affiliated Hospital of Soochow University, Suzhou City, Jiangsu, China.Department of Dermatology, The First Affiliated Hospital of Soochow University, Suzhou City, Jiangsu, China.Institute for Fetology, The First Affiliated Hospital of Soochow University, Suzhou City, Jiangsu, China.Department of Dermatology, Henan Provincial People's Hospital, Henan University People's Hospital, Zhengzhou, 450003, China.Department of Dermatology, Henan Provincial People's Hospital, Henan University People's Hospital, Zhengzhou, 450003, China.Department of Dermatology, Henan Provincial People's Hospital, Henan University People's Hospital, Zhengzhou, 450003, China.Department of Dermatology, The First Affiliated Hospital of Soochow University, Suzhou City, Jiangsu, China.Institute for Fetology, The First Affiliated Hospital of Soochow University, Suzhou City, Jiangsu, China. miaosunsuda@163.com.Department of Dermatology, The First Affiliated Hospital of Soochow University, Suzhou City, Jiangsu, China. lmpfdoctor@163.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33407466

Citation

Wang, Jianbo, et al. "Identification of a Novel Mutation in the KITLG Gene in a Chinese Family With Familial Progressive Hyper- and Hypopigmentation." BMC Medical Genomics, vol. 14, no. 1, 2021, p. 12.
Wang J, Li W, Zhou N, et al. Identification of a novel mutation in the KITLG gene in a Chinese family with familial progressive hyper- and hypopigmentation. BMC Med Genomics. 2021;14(1):12.
Wang, J., Li, W., Zhou, N., Liu, J., Zhang, S., Li, X., Li, Z., Yang, Z., Sun, M., & Li, M. (2021). Identification of a novel mutation in the KITLG gene in a Chinese family with familial progressive hyper- and hypopigmentation. BMC Medical Genomics, 14(1), 12. https://doi.org/10.1186/s12920-020-00851-5
Wang J, et al. Identification of a Novel Mutation in the KITLG Gene in a Chinese Family With Familial Progressive Hyper- and Hypopigmentation. BMC Med Genomics. 2021 01 6;14(1):12. PubMed PMID: 33407466.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Identification of a novel mutation in the KITLG gene in a Chinese family with familial progressive hyper- and hypopigmentation. AU - Wang,Jianbo, AU - Li,Weisheng, AU - Zhou,Naihui, AU - Liu,Jingliu, AU - Zhang,Shoumin, AU - Li,Xueli, AU - Li,Zhenlu, AU - Yang,Ziliang, AU - Sun,Miao, AU - Li,Min, Y1 - 2021/01/06/ PY - 2020/11/18/received PY - 2020/12/08/accepted PY - 2021/1/7/entrez PY - 2021/1/8/pubmed PY - 2021/12/15/medline KW - Familial progressive hyper- and hypopigmentation KW - KITLG gene KW - Mutation KW - VTNNV motif SP - 12 EP - 12 JF - BMC medical genomics JO - BMC Med Genomics VL - 14 IS - 1 N2 - BACKGROUND: Familial 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 eight KITLG mutations 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 the KITLG gene in two Chinese FPHH patients. METHODS: Direct sequencing of the coding regions of KITLG was 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. RESULTS: The novel mutation c.104A > T (p.Asn35Ile) and the recurrent mutation c.101C > T (p.Thr34Ile) in KITLG were 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'. CONCLUSIONS: To date, most of the identified KITLG mutations 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 in KITLG, 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 the KITLG gene. SN - 1755-8794 UR - https://wwww.unboundmedicine.com/medline/citation/33407466/Identification_of_a_novel_mutation_in_the_KITLG_gene_in_a_Chinese_family_with_familial_progressive_hyper__and_hypopigmentation_ L2 - https://bmcmedgenomics.biomedcentral.com/articles/10.1186/s12920-020-00851-5 DB - PRIME DP - Unbound Medicine ER -