泛发性萎缩性良性大疱性表皮松解症1例的基因突变研究

针对一例泛发性萎缩性良性大疱性表皮松解症（GABEB）患者进行基因突变研究，在编码大疱性类天疱疮抗原2（BPAG2）的基因COL17A1基因上发现了致病的突变，并通过等位基因特异性扩增的方法验证结果。结果显示：先证者COL17A1基因的第11外显子上有一个未被报道过的纯合性突变S265C，可能与GABEB的致病有关，先证者的父亲携带该致病突变基因，对50个正常人进行等位基因特异性扩增，未发现该突变，进一步证实S365C为该家系中的致病突变。     

Hallopeau-Siemens型隐性营养不良型大疱性表皮松解症一例的基因突变研究

目的鉴定一常染色体隐性遗传营养不良型大疱性表皮松解症家系的基因突变。方法应用PCR、DNA直接测序明确突变位点,根据突变位点设计特异性引物,用PCR检测突变位点从而进一步确定该家系的致病原因。结果发现该患者COL7A1基因的一条等位基因第2号外显子上存在S48P的错义突变,而另一条等位基因第27号外显子上存在3625del11缺失突变,造成编码区阅读框架的移位,最终导致蛋白终止密码(PTC)的产生。隐性营养不良型大疱性表皮松解症患者这种两个突变的组合在国际上为首次报道。结论 COL7A1基因的缺失突变和错义突变引起该患者临床症状的特异突变。     

一毛囊角化病家系ATP2A2基因突变检测

目的:检测一毛囊角化病家系的ATP2A2基因突变。方法:提取2例患者外周血DNA,采用聚合酶链式反应及DNA直接测序方法,检测患者ATP2A2基因突变。结果:该家系患者及其两女儿存在ATP2A2基因的碱基缺失突变,即ATP2A2基因第10个外显子1220位开始缺失了AA 2个碱基。而该家系中其他正常者未发现此突变。结论:ATP2A2基因第10个外显子1220delAA突变可能与该家系患者临床表型有关。     

先天性厚甲症2家系中角蛋白16和17的基因突变

目的了解先天性厚甲症Ⅰ型(PC-Ⅰ)及Ⅱ型(PC-Ⅱ)患者家系的基因突变。探讨其基因突变和临床表现的关系。方法扩增外周血基因组DNA中角蛋白16基因的第1~6外显子及K17基因的第1外显子,对PCR产物进行序列分析。结果PC-Ⅰ家系(家系1)中患者K16基因第127位密码子由CGC突变CCC,导致K16角蛋白1A区的精氨酸由脯氨酸替代(R127P);PC-Ⅱ家系(家系2)中2例患者K17基因第99位密码子由CTG突变为CCG,导致K17角蛋白1A区的亮氨酸由脯氨酸替代(L99P),而这两个家系中的正常人及与此两家系无关的50例正常人未发现此突变。结论该PC-Ⅰ家系存在角蛋白16的R127P突变,PC-Ⅱ家系存在角蛋白17的L99P突变。3例厚甲症患者检测到的2个角蛋白突变均由K16及K17发生错义突变,导致其编码的相应氨基酸由脯氨酸替代。此类突变可引发较重的临床表现,即呈现典型PC-Ⅰ型或PC-Ⅱ型,不会呈现其他较轻的临床亚型。     

遗传性对称性色素异常症家系的DSRAD基因突变

目的研究遗传性对称性色素异常症(DSH)家系中的DSRAD基因突变情况。方法收集了2个遗传性对称性色素异常症家系的外周血标本,用聚合酶链反应(PCR)扩增DSRAD基因的全部外显子并测序,检测2个家系中的患者及正常人和50例无关正常人的DSRAD基因。结果家系1中所有患者的DSRAD基因第2 565位至2 568位缺失GACT。家系2中所有患者的DSRAD基因第2 433位至2 434位均缺失AG。2家系中的正常人及50例无关正常人未发现突变。结论2个DSH家系患者均有DSRAD基因突变,可能由此引起编码蛋白的结构和功能改变,致皮肤色素异常。     

家族性良性天疱疮患者ATP2C1基因突变研究

目的 探讨3个家族性良性天疱疮家系和1例散发患者的ATP2C1基因突变。方法 采取家系中患病成员外周血,应用外周血细胞DNA抽提、PCR扩增和DNA直接测序等方法检测ATP2C1基因突变情况,用反向测序验证突变,用100例无血缘关系个体作正常人对照。结果 在2个家族性良性天疱疮家系和1例散发患者中发现3个未曾报道的错义突变。家系1第20外显子2048位碱基G→A,导致错义突变R619K;家系2第8外显子853位碱基A→C,导致错义突变T221P;散发患者第23外显子2323位碱基T→C,导致错义突变Y711H。家系中非患病成员和100例无血缘关系正常人均未发现这些改变。在1个家族性良性天疱疮家系未检测到基因突变。结论 发现家族性良性天疱疮3种新的ATP2C1基因突变位点。     

Hallopeau-Siemens型常染色体隐性遗传大疱性表皮松解症一家系的基因突变研究

目的鉴定一Hallopeau—Siemens型常染色体隐性遗传真皮型大疱性表皮松解症家系的基因突变，为进一步开展产前诊断奠定基础。方法提取患者及其父母的基因组DNA，应用聚合酶链反应、DNA直接测序明确突变位点，并使用限制性片段长度多态性分析进一步确定该家系的致病原因。结果发现患者COL7A1基因存在2个突变：①第12号外显子上第4326位碱基由胞嘧啶突变为胸腺嘧啶，使第525位氨基酸由精氨酸（G）突变为终止密码（R525X）；②第105号外显子上第27716位碱基由胞嘧啶突变为胸腺嘧啶，使第2510位氨基酸由精氨酸（G）突变为终止密码（R2510X）。其母为R525X突变杂合子，其父为R2510X突变杂合子。结论COL7A1基因的R525X无义突变和R2510X无义突变是引起该患者临床症状的特异突变。     

两个X连锁鱼鳞病家系中类固醇硫酸酯酶基因缺失

检测2个中国X连锁鱼鳞病家系中的基因突变。用PCR方法扩增类固醇硫酸酯酶(STS)基因的10个外显子，并对扩增产物进行测序。第一个家系中先证者的STS基因6、7外显子缺失，第二个家系先证者的整个STS基凶缺失。本研究明确了这两个家系中的基因突变，从而为这两个家系的后代进行产前诊断提供了可能。     

Hallopeau-Siemens型营养不良型大疱性表皮松解症一例产前诊断

目的 鉴定一常染色体隐性遗传营养不良型大疱性表皮松解症家系的突变后,对患者的下一代开展产前诊断.方法 首先对患者和患者妻子进行COL7A1基因全部118个外显子的扩增和直接测序.然后从孕15周患者妻子的羊水中提取胎儿的DNA,应用聚合酶链反应(PCR)、DNA直接测序和限制性片段长度多态性(RFLP)的方法来检测突变位点,从而进一步确定该胎儿是否患病.结果 发现该患者COL7A1基因的1条等位基因第2号外显子上存在S48P的错义突变,而另1条等位基因第27号外显子上存在3625del11缺失突变,造成编码区阅读框架的移位,最终导致蛋白终止密码(PTC)的产生.患者妻子该基因全序列完全正常.胎儿COL7A1基因的1条等位基因第27号外显子上存在3625del11缺失突变,而另1个第2号外显子序列正常.因此证实该胎儿为携带者,胎儿出生后临床表型正常.结论 完成我国首例常染色体隐性遗传的营养不良型大疱性表皮松解症的DNA基础的产前诊断.     

多发性皮脂腺囊肿一家系角蛋白17基因突变检测

目的 研究多发性皮脂腺囊肿一家系中角蛋白17的基因突变情况。方法 收集1个多发性皮脂腺囊肿家系中3例患者及3例表型正常者和50例无亲缘关系健康个体的外周血标本,采用PCR结合DNA直接测序检测角蛋白17基因突变。结果 该家系患者角蛋白17基因上第428位碱基胞嘧啶（C）突变为胸腺嘧啶（T）,使角蛋白17基因的第1号外显子94位密码子由CGC突变成TGC,第94位精氨酸被组氨酸取代,即R94C突变,而该家系的正常人对照及无亲缘关系健康个体不存在此突变。结论 本多发性皮脂腺囊肿家系患者角蛋白17基因存在错义突变（428C→T）,这可能是导致多发性皮脂腺囊肿发病的分子机制之一。     

New fillers for the new man

ABSTRACT:  Two new collagen-based lidocaine-containing dermal fillers, ArteSense™/ArteFill™ (Artes Medical, San Diego, CA) and Evolence® (Colbar LifeScience Ltd., Herzliya, Israel), have proved to be of particular interest to men, many of whom seek a long-lasting or permanent correction. ArteFill™ has been available in the United States since 2006, and it is expected that Evolence® will reach the American market in 2008. The properties of the two products will be described, and experience based on the administration of many hundreds of syringes of both products by a Canadian dermatologist will be detailed here, with tips and precautions to optimize patient outcomes.     

Outcomes and adverse effects of ablative vs nonablative lasers for skin resurfacing: A systematic review of 1093 patients

It is generally believed that ablative laser therapies result in prolonged healing and greater adverse events when compared with nonablative lasers for skin resurfacing. To evaluate the efficacy of ablative laser use for skin resurfacing and adverse events as a consequence of treatment in comparison to other modalities, a PRISMA‐compliant systematic review (Systematic Review Registration Number: 204016) of twelve electronic databases was conducted for the terms “ablative laser” and “skin resurfacing” from March 2002 until July 2020. Studies included meta‐analyses, randomized control trials, cohort studies, and case reports to facilitate evaluation of the data. All articles were evaluated for bias. The search strategy produced 34 studies. Of 1093 patients included in the studies of interest, adverse events were reported in a total of 106 patients (9.7%). Higher rates of adverse events were described in nonablative therapies (12.2% ± 2.19%, 31 events) when compared with ablative therapy (8.28% ± 2.46%, 81 events). 147 patients (13.4%) reported no side effects, 68 (6.22%) reported expected, transient self‐resolving events, and five (0.046%) presented with hypertrophic scarring. Excluding transient events, ablative lasers had fewer complications overall when compared with nonablative lasers (2.56% ± 2.19% vs 7.48% ± 3.29%). This systematic review suggests ablative laser use for skin resurfacing is a safe and effective modality to treat a range of pathologies from photodamage and acne scars to hidradenitis suppurativa and posttraumatic scarring from basal cell carcinoma excision. Further studies are needed, but these results suggest that ablative lasers are a superior, safe, and effective modality to treat damaged skin.     

Genetic alterations in RAS‐regulated pathway in acral lentiginous melanoma

Studies integrating clinicopathological and genetic features have revealed distinct patterns of genomic aberrations in Melanoma. Distributions of BRAF or NRAS mutations and gains of several oncogenes differ among melanoma subgroups, while 9p21 deletions are found in all melanoma subtypes. In the study, status of genes involved in cell cycle progression and apoptosis was evaluated in a panel of 17 frozen primary acral melanomas. NRAS mutations were found in 17% of the tumors. In contrast, BRAF mutations were not found. Gains of AURKA gene (20q13.3) were detected in 37.5% of samples, gains of CCND1 gene (11q13) or TERT gene (5p15.33) in 31.2% and gains of NRAS gene (1p13.2) in 25%. Alterations in 9p21 were identified in 69% of tumors. Gains of 11q13 and 20q13 were mutually exclusive, and 1p13.2 gain was associated with 5p15.33. Our findings showed that alterations in RAS‐related pathways are present in 87.5% of acral lentiginous melanomas.     

Self‐resolving superficial primary cutaneous mucormycosis in a 7‐week‐old infant

A 7‐week‐old girl, born at 30 weeks' gestational age, presented to clinic for evaluation of a crop of vesicular lesions that were noted after removal of a bandage that had been in place for 4 days. A punch biopsy of the lesion revealed fungal elements that were later identified as Rhizopus spp. The lesion began to self‐resolve, and no further treatment was needed, with full resolution of the lesion by 1 month after presentation. Clinicians should be aware of the variable presentations of mucormycosis and consider fungal infection in the differential diagnosis when evaluating vulnerable patients with skin eruptions.     

Multiple New-Onset Subcutaneous Nodules of the Upper Extremity Digits: Giant Cell Tumor of Tendon Sheath and Lipoma

A black woman with the concurrent onset of two subcutaneous nodules located on the digits of her upper extremities is described. Initially, a single systemic disorder was considered; yet, the lesions differed in morphology and consistency. Microscopic examination of the nodules showed a giant cell tumor of tendon sheath and a lipoma. Although Occam's “razor” suggests that multiple lesions in the same person are more likely to represent variable manifestations of a single disorder than several different diseases in that individual, the simultaneously appearing lesions in this patient represented two different conditions.