Novel pathogenic variants in KIT gene in three Chinese piebaldism patients

Chen Wang; Yingzi Zhang; Xuyun Hu; Lijuan Wang; Zhe Xu; Huan Xing

doi:10.3389/fmed.2022.1040747

Novel pathogenic variants in KIT gene in three Chinese piebaldism patients

Front Med (Lausanne). 2022 Nov 10:9:1040747. doi: 10.3389/fmed.2022.1040747. eCollection 2022.

Authors

Chen Wang¹, Yingzi Zhang², Xuyun Hu³, Lijuan Wang¹, Zhe Xu¹, Huan Xing¹

Affiliations

¹ Department of Dermatology, National Center for Children's Health, Beijing Children's Hospital, Capital Medical University, Beijing, China.
² Department of Dermatology, Shunyi Maternal and Children's Hospital of Beijing Children's Hospital, Beijing, China.
³ Beijing Key Laboratory for Genetics of Birth Defects, MOE Key Laboratory of Major Diseases in Children, Genetics and Birth Defects Control Center, National Center for Children's Health, Beijing Children's Hospital, Beijing Pediatric Research Institute, Capital Medical University, Beijing, China.

Abstract

Background: Piebaldism is a rare autosomal dominant disease, and roughly 75% patients had KIT gene mutations. Up to date, approximately 90 KIT mutations causing piebaldism were reported.

Methods: To identify KIT gene mutations in three pediatric piebaldism patients from different families and explore the genotype-phenotype correlation, peripheral blood DNA were collected from probands and their parents. Whole-exome sequencing was performed to detect potential disease-causing variants in the three probands. Putative variants were validated by Sanger sequencing.

Results: Heterozygous variants of c.2469_2484del (p.Tyr823*), c.1994G > C (p.Pro665Leu), and c.1982_1983insCAT (p.662_663insIle) in KIT gene were detected in three probands. These variants were all novel and classified as pathogenic/likely pathogenic variants according to the interpretation guidelines of American College of Medical Genetics and Genomics and the Association for Molecular Pathology. The probands carrying variants located in tyrosine kinase domain exhibited a more severe phenotype.

Conclusion: The piebaldism in three families was caused by novel heterozygous KIT variants. The severity of phenotypes is related with the types and locations of different mutations. Our results further provided evidence for genetic counseling for the three families.

Keywords: KIT gene; café-au-lait macule; genotype-phenotype correlation; piebaldism; whole-exome sequencing.