British Journal of DermatologyVolume 155, Issue 6 p. 1303-1304 New mutations of KIT gene in two Chinese patients with piebaldism Z-M. Lin, Z-M. Lin Peking University First Hospital, and Beijing Children's Hospital, Dermatology, Beijing, ChinaSearch for more papers by this authorZ. Xu, Z. Xu Peking University First Hospital, and Beijing Children's Hospital, Dermatology, Beijing, ChinaSearch for more papers by this authorD-F. Bu, D-F. Bu Peking University First Hospital, and Beijing Children's Hospital, Dermatology, Beijing, ChinaSearch for more papers by this authorY. Yang, Y. Yang Peking University First Hospital, and Beijing Children's Hospital, Dermatology, Beijing, ChinaSearch for more papers by this author Z-M. Lin, Z-M. Lin Peking University First Hospital, and Beijing Children's Hospital, Dermatology, Beijing, ChinaSearch for more papers by this authorZ. Xu, Z. Xu Peking University First Hospital, and Beijing Children's Hospital, Dermatology, Beijing, ChinaSearch for more papers by this authorD-F. Bu, D-F. Bu Peking University First Hospital, and Beijing Children's Hospital, Dermatology, Beijing, ChinaSearch for more papers by this authorY. Yang, Y. Yang Peking University First Hospital, and Beijing Children's Hospital, Dermatology, Beijing, ChinaSearch for more papers by this author First published: 24 October 2006 https://doi.org/10.1111/j.1365-2133.2006.07560.xCitations: 8 Y. Yang.E-mail: yongyang81@yahoo.com.cn Conflicts of interest: none declared. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume155, Issue6December 2006Pages 1303-1304 RelatedInformation

OBJECTIVE:Inherited erythermalgia (erythromelalgia) is an autosomal dominant disorder in which patients experience severe burning pain in the extremities, in response to mild thermal stimuli and exercise. Although mutations in sodium channel Na(v)1.7 have been shown to underlie erythermalgia in several multigeneration families with the disease that have been investigated to date, the molecular basis of erythermalgia in sporadic cases is enigmatic. We investigated the role of Na(v)1.7 in a sporadic case of erythermalgia in a Chinese family.METHODS:Genomic DNA from patients and their asymptomatic family members were sequenced to identify mutations in Na(v)1.7. Whole-cell patch clamp analysis was used to characterize biophysical properties of wild-type and mutant Na(v)1.7 channels in mammalian cells.RESULTS:A single amino acid substitution in the DIIS4-S5 linker of Na(v)1.7 was present in two children whose parents were asymptomatic. The asymptomatic father was genetically mosaic for the mutation. This mutation produces a hyperpolarizing shift in channel activation and an increase in amplitude of the response to slow, small depolarizations.INTERPRETATION:Founder mutations in Na(v)1.7, which can confer hyperexcitability on peripheral sensory neurons, can underlie sporadic erythermalgia.

OBJECTIVE:To identify the DSRAD gene; mutations in three Chinese families with dyschromatosis symmetrica hereditaria.METHODS:All exons of DSRAD gene were analyzed in each person of these families with PCR-DNA sequencing. DNA samples from 100 unrelated, normally pigmented adult individuals were also included as control.RESULTS:We identified a missense mutation of C3220T (R1074C) in DSRAD gene in family A, and another missense mutation of G3325T (D1109Y) in DSRAD gene in family B and C. No same mutation was found in unaffected individuals in the families and the controls.CONCLUSION:We found two special missense mutations in DSRAD gene in three families of dyschromatosis symmetrica hereditaria. These mutations may impair DSRAD protein function, and as a consequence, cause skin dyschromatosis.

BACKGROUND:Xeroderma pigmentosum (XP) is a group of autosomal recessive diseases characterized by hypersensitivity to ultraviolet rays. Among its eight complementation groups, XP group A (XPA) is the most severe type. The XPAC gene has been identified as the defective gene in XPA patients.OBJECTIVES:To examine genomic DNA from a Chinese family with XPA, to determine the XPAC mutation and, after genetic counselling, to undertake DNA-based prenatal diagnosis in a subsequent pregnancy.METHODS:Fetal DNA was extracted from amniotic fluid and used to amplify exon 5 of XPAC containing the potential mutation. Direct sequencing and restriction endonuclease digestion were used for prenatal diagnosis.RESULTS:We identified a homozygous nonsense XPAC mutation of 631C-->T, which results in an R211X mutation in XPA protein, in the proband. Both her parents are heterozygous. Prenatal diagnosis demonstrated a heterozygous sequence predicting an unaffected child, and a healthy girl was born.CONCLUSIONS:These data provide the first example of a DNA-based prenatal test for genodermatosis in China.

A new missense mutation in the keratin 5 gene (KRT5) in a Chinese family with Weber-Cockayne type epidermolysis bullosa simplex is reported. Direct sequencing identified a heterozygous A --> C substitution at nucleotide 596 altering codon 199 of KRT5 from lysine to threonine in all affected family members, but not in the unaffected family members or in 50 unrelated control samples. The mutation is designated K199T. This mutated lysine residue is sited within the 1A domain of keratin 5 and is highly conserved among all type II keratins. The mutation may perturb the alignment of tonofilaments and, as a consequence, result in skin fragility and blistering.

Research in the field of genetic skin disease has grown rapidly over the past two decades. Even though the fundamental molecular pathways are still not fully understood, there have prominent advances in our understanding of the underlying mechanisms involved in the pathogenesis of genodermatosis. Dermatologists in China contributed to this field in recent years. They found the causative genes involved in primary erythermalgia and familial trichoepithelioma. Different gene mutations involved in more than twenty kinds of genodermatosises have been detected. This review will synthesize recent findings of the genodermatosises in China.

目的 对原发性红斑性肢痛症的致病基因进行定位及突变研究.方法收集一个原发性红斑性肢痛症家系成员和一个散发病例的血样抽提基因组DNA.选用2号染色体长臂上已知致病区域的6个微卫星标记对该家系成员进行基因扫描,并对基因分型结果进行连锁分析及单倍型分析.PCR扩增SCN9A基因的全部外显子,并进行测序.针对所发现的突变以Hph Ⅰ、BsrS Ⅰ内切酶行限制性片段长度多态性(RFLP)分析.结果连锁分析结果发现本家系在微卫星标记D2S2370和D2S2330的两点最大LOD值为2.11(重组率=0.00),单倍型分析发现本家系在微卫星标记D2S1353和D2S2345存在重组.家系患者和散发病例均存在SCN9A基因第15外显子的错义杂合点突变:家系全部患者均存在T2573A杂合突变,散发病例存在T2543C杂合突变,分别导致Nav1.7第858位的亮氨酸被替换为组氨酸(L858H)及第848位的异亮氨酸被苏氨酸替换(I848T).RFLP证实了正常对照无此突变.结论在世界上首次证明SCN9A基因是原发性红斑性肢痛症的候选致病基因。

OBJECTIVE:To clone and express xeroderma pigmentosum, complementation group A (XPA) cDNA and to identify its recombinant protein.METHODS:Coding region of XPA cDNA was amplified from human tonsil cDNA by reverse transcription and nested PCR. The PCR product was cloned into pBluescript vector, confirmed by DNA sequencing, cloned in frame into a prokaryotic expression vector pTrcHis C and expressed in E. coli. TOP10. The recombinant fusion protein was identified by immunoblotting.RESULTS:The entire coding region of XPA cDNA was cloned and expressed. The fusion XPA protein was identified by anti-XPA monoclonal antibody on western blot.CONCLUSION:Cloning of human XPA cDNA and successful expression of recombinant XPA protein will be useful for the construction of a viral gene transfer vector for the gene therapy of XPA.