毛囊角化病ATP2A2基因突变分析

目的检测毛囊角化病患者ATP2A2基因的突变。方法提取全部患者及健康对照个体的外周血DNA,采用聚合酶链反应扩增ATP2A2基因的全部外显子,并进行DNA测序。结果在收集到的2个家系和3例散发患者中共发现3个突变,包括1个缺失突变(1622delAACA),1个插入突变(180insCTTAA)和1个错义突变(698GT),均为未见报道的突变。在100例正常对照中均未发现上述突变。结论收集到的毛囊角化病患者存在ATP2A2基因的突变,这些突变可能会影响角质形成细胞中钙离子的转运,使表皮细胞的连接和分化出现异常。     

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。     

一毛囊角化病家系ATP2A2基因突变的检测

目的 检测一毛囊角化病家系中ATP2A2基因的突变。方法 1例经组织病理结合临床诊断为毛囊角化病,采用聚合酶链反应和DNA测序方法对此家系进行基因突变情况检测。结果 家系中患者在ATP2A2上第1541位腺嘌呤A变为鸟嘌呤G,使编码ATP酶结合域第514位氨基酸由赖氨酸变为精氨酸,家系中未患病者及对照的健康人均不存在此突变。结论 K514R是引起该家系临床病变的一个新的特异突变,不是多态性变化。     

毛囊角化病一家系及三例散发患者ATP2A2基因突变研究

目的：对毛囊角化病（Darier's disease, DD）一家系及三例散发患者进行ATP2A2基因的突变分析。方法：收集先证者及其家系成员、散发病例的临床资料和外周血,采用PCR技术扩增ATP2A2基因所有编码区及侧翼序列,用Sanger法测序检测潜在的突变,选取与患者无亲缘关系的100例健康人作为对照,同时对已报道的ATP2A2基因突变进行文献回顾。结果：家系中三例患者均检测出ATP2A2基因第5号外显子c.380 G>A(p.G127D)新发错义突变;散发患者S1检测出第13号外显子C.1676G>A(p.R559Q)错义突变,散发患者S2检测出第14号外显子c. 2001C>T(p.D667D)同义突变,散发患者S3未检测出突变。结论：本研究中共发现三个突变,其中c.380G>A(p.G127D)在中国人群中首次报道,拓展了ATP2A2的基因突变谱。     

毛囊角化病患者ATP2A2基因新剪切位点突变的检测研究

目的:检测1例严重表型毛囊角化病患者ATP2A2基因的突变.方法:采用聚合酶链反应及直接测序法对该患者进行ATP2A2基因的突变位点检测,运用反转录技术检测突变导致的RNA水平的变化,同时对120名无血缘关系健康者作为对照进行测序验证.结果:通过筛查在患者ATP2A2基因中发现一个新的剪切位点突变IVS18+5G＞C,反转录分析证实该突变的发生导致ATP2A2基因转录后在其突变等位基因的18号和19号外显子之间插入了27个核苷酸.结论:该例毛囊角化病患者的检测结果进一步扩充了ATP2A2基因的突变库,并为阐明ATP2A2基因的突变导致该病发生的分子机制提供了帮助.     

毛囊角化病九例ATP2A2基因突变研究

目的:检测9例毛囊角化病(Darier's disease,DD)患者的基因突变.方法:提取1家系中2例患者、7例散发患者及100名正常对照外周血基因组DNA,用Sanger测序检测9例DD患者ATP2A2的致病突变.对不携带ATP2A2突变的患者,应用全外显子组测序(WES)寻找可能导致该疾病的其他变异.364名健康...     

毛囊角化病ATP2A2基因突变二例及家系调查

【摘要】 例1男,16岁,面部、颈部及双腋下见密集褐色毛囊角化性丘疹,部分融合成斑块,局部可见疣状增生;母亲与其有相似的病史及临床表现。例2男,21岁,头面部、颈部、躯干、双腋下及臀部见弥漫性毛囊角化性丘疹,部分融合成片,局部可见疣状增生;家族成员均无类似症状。例2颈部皮损组织病理：表皮角化过度伴灶状角化不全,棘层部分区域棘刺松解并有腔隙形成,可见绒毛、圆体和谷粒细胞,真皮浅层炎症细胞浸润。2例患者及其父母基因检测：例1及母亲ATP2A2基因存在第15外显子c.2300A>G错义突变;例2第15外显子与第15内含子交界处存在c.2097+5G>A 剪切区域突变。2例患者其他家族成员未见上述突变。     

毛囊角化病一家系中ATP2A2基因新的剪接突变

目的: 检测毛囊角化病一家系中ATP2A2基因新的剪接突变。方法: 提取家系中2例患者和2名正常人外周血DNA,采取聚合酶链反应技术对ATP2A2基因进行扩增,并对其产物进行测序,以100名正常人作对照。结果:该家系中患者ATP2A2基因的第13号内含子第1761+2位碱基由胸腺嘧啶(T)转化为胞嘧啶(C)。结论: 该家系发病可能是由ATP2A2基因发生剪接突变所致。     

哈萨克族毛囊角化病一家系ATP2A2基因突变研究

目的 探讨哈萨克族毛囊角化病一家系患者ATP2A2基因突变.方法 收集哈萨克族毛囊角化病49人家系的临床资料,采集44名家系成员和100例无亲缘关系健康人外周血,提取基因组DNA.采用PCR和DNA测序对该家系进行ATP2A2基因突变检测.结果 该家系毛囊角化病遗传方式属于常染色体显性遗传.家系中11例患者在ATP2A2基因12号外显子的剪切位点发生杂合突变(1288-1G→A),即第1288-1位碱基由G突变为A,而家系中33例正常成员及100例健康对照均未发现该突变.结论 该家系毛囊角化病发病可能是由ATP2A2基因12号外显子的剪切位点发生杂合突变(1288-1G→A)所致.     

阿维A酸治疗毛囊角化病2例

毛囊角化病是一种临床上较少见的皮肤病。我科曾于2002年用阿维A酸（商品名：新体卡松，上海罗氏制药有限公司）治疗2例毛囊角化病患者，并取得了满意疗效，现报告如下。     

Mutation analysis of the ATP2A2 gene in Taiwanese patients with Darier's disease

BACKGROUND: Darier's disease (DD) is an autosomal dominant skin disorder characterized by abnormal keratinization and acantholysis. Pathogenic mutations in the ATP2A2 gene encoding SERCA2, a calcium pump of the sarco/endoplasmic reticulum, have recently been identified. OBJECTIVES: To identify mutations of the ATP2A2 gene in Taiwanese patients with DD. METHODS: Mutation analysis of genomic DNA was performed on five families with DD and two sporadic cases. All 21 exons and the flanking intron boundaries were amplified and followed by direct sequencing. Restriction fragment analysis or direct sequencing in each family and in normal controls further verified the mutations. RESULTS: Mutations in the functional domains of the ATP2A2 gene were identified and verified in all seven pedigrees. They consisted of four mis-sense mutations (R131Q, P680L, G703S, G807R), one altered splice-site mutation (2980 + 5insA) and one frameshift deletion mutation (1457-1458delAG). Of these, R131Q, which was reported twice previously, was detected in two unrelated families. The remaining five were novel mutations. CONCLUSIONS: Six pathogenic mutations in the ATP2A2 gene were identified in seven Taiwanese DD pedigrees. The results confirmed that most mutations in the ATP2A2 gene are private and of the mis-sense type.     

The ATP2A2 gene in patients with Darier's disease: one novel splicing mutation

Background Darier’s disease (DD) is a rare, inherited skin disorder characterized by warty papules and plaques over the seborrheic area, such as central trunk, flexures, scalp, and forehead. Mutations in ATP2A2 gene encoding the enzyme sarco/endoplasmic reticulum Ca²⁺ATPase type 2 are responsible for the disease. Here we report two Chinese families affected by DD with two ATP2A2 mutations. Materials and methods DNA was extracted from the peripheral blood samples and then subjected to polymerase chain reaction amplification and direct automated DNA sequencing. Results A heterozygous G to T transition in the first nucleotide of intron 7 (c.630 + 1G > T) and G to A transversion at nucleotide 2898 in exon 20 of the ATP2A2 gene were identified in two pedigrees, respectively. The former mutation in the splice site is a novel mutation and is thought to lead to aberrant splicing and premature protein truncation. The latter has already been described, which leads to premature termination codons (PTC) (W966X). Conclusion The results will contribute to the expanding database of ATP2A2 mutations in patients with DD and be useful for inherited counseling and prenatal examination for affected families.     

Novel mutations of ATP2A2 gene in Japanese patients of Darier's disease

Darier's disease (DD) is a rare, dominantly inherited skin disorder with abnormal keratinization and acantholysis. Recently, mutations of ATP2A2 encoding the sarco/endoplasmic reticulum Ca(2+)-ATPase type 2 isoform (SERCA2) have been reported in Caucasian DD families. In the present study, we examined the ATP2A2 gene mutations of three sporadic (AS1,AS3,AS4) and one familial (AS2) Japanese DD patients. Sequence analysis revealed that the patients had novel mutations, one nonsense mutation (AS1 (C613X)) and three single base changes leading to amino acid substitutions (AS2 (L321F), AS3 (I274V), and AS4 (M719I)). These results demonstrate that distinct ATP2A2 gene mutations are present in Japanese DD patients.     

Identification of mutations in the ATP2A2 gene in patients with Darier's disease from Hungary

Mutation analysis in the ATP2A2 gene had been performed in eight Hungarian patients with Darier's disease (DD), to get more information about phenotype-genotype relations. All patients had moderate to severe skin symptoms. Polymerase chain reaction (PCR) amplification of the entire coding region of ATP2A2 was performed. Mutation detection strategies included heteroduplex scanning by conformation-sensitive gel electrophoresis (CSGE) and direct nucleotide sequencing. We found distinct, heterozygous mutations (five missense, one nonsense, one deletion, and one insertion), six of which were novel. In a 31-year-old DD woman with learning difficulties we disclosed a previously described missense mutation (D702N) in exon 15. A 44-year-old DD woman had a novel T insertion at nucleotide 559 in exon 7 of the ATP2A2 gene, which resulted in a premature termination codon (PTC) at codon 192. A woman, whose skin symptoms developed unusually late, at the age 50, had a new T deletion (1320delT) in exon 11 resulting in a PTC at codon 448. Our most severe case had a known missense mutation N39T, resulting in a non-conservative amino acid change at the upstream stalk region. Three new missense mutations (A161D, R164S, and Q790P) affected conservative regions of the SERCA2 protein within the activation (A)-domain and the M6 transmembrane region. A further new nonsense mutation (C909X) was detected in the M8 transmembrane domain. Our data suggest that differences in DD phenotypes are probably also related to factors different from the type of causative mutation.