1例斑驳病大家系临床表型及基因突变研究

Study on the clinical phenotype and genotype of a case of mottle disease

目的研究1例中国汉族斑驳病大家系临床表型及其KIT基因的突变情况。方法收集1例斑驳病家系3代14人所有患者及健康个体的临床资料和血样,提取所有样本以及100例健康对照的外周血基因组DNA,用PCR扩增KIT基因所有的外显子并进行Sanger测序。结果先证者前额可见菱形分布的白斑横跨发际线,白斑处头发发白,前胸、腹部、四肢可见脱色素斑,部分白斑周边可见数个色素沉着斑;此外,左小腹部可见深褐色咖啡斑。先证者外公、大姨及姐姐有不同程度发病,先证者母亲未见皮损;在该家系患者中均检测到KIT基因的错义突变c.272A> T(p.Asn91Ile)。在家系内的先证者健康母亲也检测到KIT基因的错义突变c.272A>T。100例健康对照及家系内其他健康者中均未发现上述突变。c.272A>T未见文献报道。结论斑驳病患者的临床表型存在不一致性,一种新的KIT基因突变(c.272A>T,p.Asn91Ile)可能是引起该斑驳病家系临床表型的原因,该家系存在遗传异质性。

Objective To investigate the clinical phenotype and KIT gene mutation in a Chinese Han pedigree with piebaldism. Methods Clinical data and blood samples were collected from 14 individuals from 3 generations of the piebaldism family.Peripheral blood genomic DNA of all samples and 100 healthy controls were extracted.All exons of the KIT gene were amplified by PCR and sequenced by Sanger sequencing. Results There were rhomboid distribution of white spots across the hairline on the forehead of the proband,white hair on the white spots,depigmentation spots on the chest,abdomen and limbs,and several pigmentation spots around some white spots.In addition,dark brown coffee spots can be seen in the left midsection.The grandfather,aunt and sister of the proband had different degrees of disease,and the mother of the proband had no skin lesions.Missense mutation c.272A> T(p.sn91ile) of KIT gene was detected in all patients and the healthy mother of the proband in this pedigree with piebaldism.No mutations were found among 100 healthy controls and other healthy members of this predigree.The mutation c.272A>T (p.Asn91Ile) of KIT gene had not been reported in the literature. Conclusion The clinical phenotype of patients with piebaldism is inconsistent,and a novel KIT gene mutation (c.272A>T,p.sn91ile) may be the cause of the clinical phenotype this pedigree with piebaldism,which has genetic heterogeneity.