斑驳病并发多发性咖啡斑1例KIT基因突变检测
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摘要
目的:检测1例斑驳病并发多发性咖啡斑患者的KIT基因突变情况。方法:收集患者临床资料,提取患者外周血DNA,聚合酶链式反应(PCR)扩增KRT5、KRT14、ABCB6、POFUT1、POGLUT1及KIT基因编码区的全部外显子及其侧翼序列并测序,明确突变位点。结果:Sanger测序发现该例患者KIT基因14号外显子的第2017位碱基发生T→G杂合突变(c.2017T>G),导致其编码第673位氨基酸发生错义突变(p.C673G)。其余上述基因均未发现致病性突变。结论:该例患者最终确诊为KIT基因突变导致的斑驳病,基因检测是确诊临床表现不典型的色素遗传性疾病的重要方法。
Objective: To detect the KIT gene mutation in a case of piebaldism with multiple café-au-lait spots. Methods: Clinical data and the peripheral blood sample were collected from the patient of piebaldism with multiple café-au-lait spots. DNA was extracted from the blood sample, and PCR was performed to amplify all the exons and their flanking sequences in the coding regions of the KRT5, KRT14, ABCB6, POFUT1, POGLUT1 and KIT genes followed by DNA sequencing. Results: Sanger sequencing revealed that the patient harbored a heterozygous mutation(c.2017 T>G) in exon 14 of the KIT gene, leading to a missense amino acid substitution at position 673(p.C673G). No pathogenic mutation was found in the rest of above genes. Conclusions: The patient was eventually diagnosed with piebaldism due to KIT mutation. Genetic testing serves as an important approach for the accurate diagnosis of inherited pigmented disorders with atypical manifestations.
Objective: To detect the KIT gene mutation in a case of piebaldism with multiple café-au-lait spots. Methods: Clinical data and the peripheral blood sample were collected from the patient of piebaldism with multiple café-au-lait spots. DNA was extracted from the blood sample, and PCR was performed to amplify all the exons and their flanking sequences in the coding regions of the KRT5, KRT14, ABCB6, POFUT1, POGLUT1 and KIT genes followed by DNA sequencing. Results: Sanger sequencing revealed that the patient harbored a heterozygous mutation(c.2017 T>G) in exon 14 of the KIT gene, leading to a missense amino acid substitution at position 673(p.C673G). No pathogenic mutation was found in the rest of above genes. Conclusions: The patient was eventually diagnosed with piebaldism due to KIT mutation. Genetic testing serves as an important approach for the accurate diagnosis of inherited pigmented disorders with atypical manifestations.
引文
[1]Narita T,Oiso N,Fukai K,et al.Two children with a mild or moderate piebaldism phenotype and a father without leukoderma in a family with the same recurrent missense mutation in the kinase domain of KIT[J].Eur J Dermatol,2011,21(3):446-447.
[2]Oiso N,Fukai K,Kawada A,et al.Piebaldism[J].J Dermatol,2013,40(5):330-335.
[3]贾苇雪,李海玲,毛秋霞,等.斑驳病合并咖啡斑1例[J].中国皮肤性病学杂志,2015,29(2):174-175.
[4]Duarte AF,Mota A,Baudrier T,et al.Piebaldism and neurofibromatosis type 1:family report[J].Dermatol Online J,2010,16(1):11.
[5]Chiu YE,Dugan S,Basel D,et al.Association of piebaldism,multiple cafe-au-lait macules,and intertriginous freckling:clinical evidence of a common pathway between KIT and sprouty-related,ena/vasodilator-stimulated phosphoprotein homology-1 domain containing protein 1(SPRED1)[J].Pediatr Dermatol,2013,30(3):379-382.
[6]Park SY,Kim HJ,Ahn SK.Piebaldism with neurofibromatosis type I:a familial case[J].Ann Dermatol,2014,26(2):264-266.
[7]Spritz RA,Holmes SA,Ramesar R,et al.Mutations of the KIT(mast/stem cell growth factor receptor)proto-oncogene account for a continuous range of phenotypes in human piebaldism[J].Am J Hum Genet,1992,51(5):1058-1065.
[8]Lennartsson J,Ronnstrand L.Stem cell factor receptor/c-Kit:from basic science to clinical implications[J].Physiol Rev,2012,92(4):1619-1649.
[9]Yang B,Yang Q,Yan H,et al.A novel KIT frame-shift mutation in a large Chinese family with variably severe phenotypes of piebaldism[J].J Dermatol,2013,40(2):126-127.
[10]Janjua SA,Khachemoune A,Guldbakke KK.Piebaldism:a case report and a concise review of the literature[J].Cutis,2007,80(5):411-414.
[11]Richards KA,Fukai K,Oiso N,et al.A novel KIT mutation results in piebaldism with progressive depigmentation[J].J Am Acad Dermatol,2001,44(2):288-292.
[12]Ward KA,Moss C,Sanders DS.Human piebaldism:relationship between phenotype and site of kit gene mutation[J].Br J Dermatol,1995,132(6):929-935.
[2]Oiso N,Fukai K,Kawada A,et al.Piebaldism[J].J Dermatol,2013,40(5):330-335.
[3]贾苇雪,李海玲,毛秋霞,等.斑驳病合并咖啡斑1例[J].中国皮肤性病学杂志,2015,29(2):174-175.
[4]Duarte AF,Mota A,Baudrier T,et al.Piebaldism and neurofibromatosis type 1:family report[J].Dermatol Online J,2010,16(1):11.
[5]Chiu YE,Dugan S,Basel D,et al.Association of piebaldism,multiple cafe-au-lait macules,and intertriginous freckling:clinical evidence of a common pathway between KIT and sprouty-related,ena/vasodilator-stimulated phosphoprotein homology-1 domain containing protein 1(SPRED1)[J].Pediatr Dermatol,2013,30(3):379-382.
[6]Park SY,Kim HJ,Ahn SK.Piebaldism with neurofibromatosis type I:a familial case[J].Ann Dermatol,2014,26(2):264-266.
[7]Spritz RA,Holmes SA,Ramesar R,et al.Mutations of the KIT(mast/stem cell growth factor receptor)proto-oncogene account for a continuous range of phenotypes in human piebaldism[J].Am J Hum Genet,1992,51(5):1058-1065.
[8]Lennartsson J,Ronnstrand L.Stem cell factor receptor/c-Kit:from basic science to clinical implications[J].Physiol Rev,2012,92(4):1619-1649.
[9]Yang B,Yang Q,Yan H,et al.A novel KIT frame-shift mutation in a large Chinese family with variably severe phenotypes of piebaldism[J].J Dermatol,2013,40(2):126-127.
[10]Janjua SA,Khachemoune A,Guldbakke KK.Piebaldism:a case report and a concise review of the literature[J].Cutis,2007,80(5):411-414.
[11]Richards KA,Fukai K,Oiso N,et al.A novel KIT mutation results in piebaldism with progressive depigmentation[J].J Am Acad Dermatol,2001,44(2):288-292.
[12]Ward KA,Moss C,Sanders DS.Human piebaldism:relationship between phenotype and site of kit gene mutation[J].Br J Dermatol,1995,132(6):929-935.