Clinical Study And Gene Mutation Detection Of 1 Piebaldism Pedigree

Introduction: Piebaldism(Piebaldism)is a pigment disorder caused by melanocyte dysplasia,with an autosomal dominant genetic pattern.The incidence was less than 1:20000.Skin leucorrhea is the main clinical manifestations of this disease,among which the most characteristic clinical manifestations are the triangular or rhomboid leucorrhea occurring in the middle of the forehead,across the hairline,and the hair in the leucorrhea is white,in addition,leucorrhea can also involve the face,limbs and trunk,more symmetrical distribution;White spots usually remain stable throughout life,and pigmentation of varying degrees and sizes can occur around or even in the center of white spots in some patients.Mottling is known to be caused by mutations in the KIT gene located in the q11-12 region of chromosome 4 or the SLUG gene located on chromosome 8.Heterozygous mutations in the KIT gene are present in 75% of DSMD patients.The main function of the KIT gene is to encode tyrosine kinases containing 976 amino acids(RTK/KIT).KIT belongs to tyrosine kinase family of type III transmembrane receptor,consisting of signal sequence,extracellular ligand binding domain of amino terminal,transmembrane domain,near-membrane domain,tyrosine kinase domain 1,kinase insertion domain and tyrosine kinase domain 2.The severity of the mottling phenotype is related to the location and type of mutations in the KIT gene.In this study,a mottled disease family was selected to explore the clinical characteristics of this family and carry out gene mutation analysis,so as to improve clinicians' understanding of the disease and facilitate the family genetic counseling and prenatal diagnosis.Materials and Methods: 1.In this study,a total of 3 individuals from 2 generations of 1 mottled disease family were included.All patients were examined by two or more experienced dermatologists for detailed medical history and physical examination,the examination results were recorded,and the family map was drawn.2.Peripheral venous blood of family members was extracted to extract genomic DNA.The genomic DNA of the proband was captured by total exome and sequenced by high-throughput sequencing,and the candidate mutation sites were verified by Sanger sequencing in DNA samples from the family.3.Bioinformatics software PolyPhen2 and mutation taster were used to predict the function of suspected pathogenic mutation sites in the family.Results: 1.The family map was drawn to show that there were patients in each generation of the family,which was in accordance with the autosomal dominant inheritance law.A white spot appears on the forehead of the proband from birth,straddling the hairline,and the hair in the spot is white.A few white spots on the left leg and more white spots on the right leg;The proband's mother had white spots on both lower extremities.The clinical manifestations of the patients in the family line were typical of mottling.2.By the verification of total exome sequencing and Sanger sequencing,we identified a missense mutation c.2424 T >g(p.ile808met)of a KIT gene,which was a new mutation site,and it has not been reported in the literature and database at present.Conclusion: We report a family with mottling caused by a new mutation site in a KIT gene.