A novel c.2326G>A KIT pathogenic variant in piebaldism
Weili Shi1,2, Ke Yang1, Yafei Sun2
1Henan Provincial People's Hospital, Medical Genetics Institute of Henan Province, Henan Provincial Key Laboratory of Genetic Diseases and Functional Genomics, People's Hospital of Zhengzhou University, People's Hospital of Henan University Zhengzhou 450003, P. R. China.
American Journal of Translational Research
|November 16, 2020
Summary
A novel pathogenic variant in the KIT gene was identified in a family with piebaldism. Functional studies confirmed KIT signaling dysfunction, aiding genetic counseling and prenatal diagnosis.
Area of Science:
- Genetics
- Molecular Biology
- Dermatology
Background:
- Piebaldism is a rare genetic disorder causing congenital depigmentation.
- The KIT gene is a primary cause, but its exact role in piebaldism is not fully understood.
Purpose of the Study:
- To identify the genetic cause of piebaldism in a familial case.
- To investigate the molecular mechanism of a novel KIT variant.
Main Methods:
- Whole exome sequencing and Sanger sequencing were employed for variant identification and validation.
- Functional studies in HEK293T cells assessed KIT signaling pathway activity via STAT5 phosphorylation.
- Prenatal diagnosis was performed for the affected family.
Main Results:
- A novel pathogenic KIT variant (c.2326G>A) was identified in the family.
- Mutant KIT showed reduced STAT5 phosphorylation, indicating dysfunctional KIT signaling.
- Prenatal diagnosis confirmed the fetus inherited the pathogenic variant.
Conclusions:
- A new pathogenic KIT variant expands the known spectrum of mutations causing piebaldism.
- The identified variant impairs KIT signaling, contributing to piebaldism pathogenesis.
- Findings enhance genotype-phenotype correlations and support genetic counseling and prenatal diagnosis.
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