点状掌跖角化病遗传学研究进展

点状掌跖角化病是一种以掌跖部不规则分布、进行性加重的角化性丘疹为特征的常染色体显性遗传性皮肤病.目前已报道AAGAB基因和COL14A1基因是点状掌跖角化病致病基因,除此之外,可能还存在其他致病基因.迄今为止,在多个种族或民族点状掌跖角化病家系中已发现39种AAGAB基因突变和1个COL14A1基因突变位点.AAGAB基因突变导致其编码的p34蛋白功能缺失或不足,使表皮生长因子受体再循环发生障碍,角质形成细胞发生过度增殖,导致点状掌跖角化病发生.COL14A1基因突变的致病性有待于蛋白质功能学研究、体外细胞实验以及该基因突变在其他点状掌跖角化病家系内重复性验证等进一步证实.     

中国汉族人6家系42例进行性对称性红斑角化症的临床和遗传特点分析

目的：了解中国汉族人进行性对称性红斑角化症(PSEK)的临床表型和遗传学特点。方法：对我们收集的一个PSEK家系中患者的临床表型和遗传特点进行总结和分析，并将结果与1980年以来文献报道的5个中国汉族人PSEK家系进行系统对比分析。结果：(1)PSEK在家系中的传递符合常染色体显性遗传模式；(2)中国汉族人群中PSEK的临床表型特征为初发于掌跖的固定、边界清楚的角化性红色斑块，对称分布，部分患者皮损可扩展至四肢近端及躯干等处，但多局限，不影响患者健康，多幼年发病；(3)同一家系中不同患者的表现度可存在明显差异；(4)患者多不伴发其他疾病；(5)部分家系的发病情况呈现不规则显性。结论：PSEK是一种具有高外显率的常染色体显性遗传性皮肤病，中国汉族人群中报道不多；临床表型以对称分布的散在、固定的角化性红色斑块为特征，但不同患者表现度可存在差异。     

五个汗孔角化病家系的临床和遗传特点

目的 调查5个3种类型汗孔角化病家系的临床和遗传资料,进而分析3种类型汗孔角化病的临床表现和遗传特点。方法 当5个家系先证者的临床诊断明确后(主要诊断依据是特征性皮损和组织病理),现场调查家系资料,对每个家系的家庭成员进行相关临床检查和遗传调查。这5个家系包括3个播散性浅表光线性汗孔角化病(DSAP,共266人,其中患者100例)家系,1个散发性跖汗孔角化病及播散性汗孔角化病(PPPD,共90人,其中患者26例)家系和1个经典斑块型(PM,共34人,其中患者17例)家系。结果 5个家系都为常染色体显性遗传,都具有以边缘呈堤状隆起、中央萎缩的典型皮损,有角化不全细胞柱的病理变化。可分为3种亚型,每一类型各有自身特色。DSAP型是汗孔角化病的一种常见类型,疾病初发年龄较其他类型早(一般8-20岁),初发皮损在颜面部。PPPD型初发年龄为14-20岁,初发皮损为掌跖部或面部,初发皮损为掌跖部者病情较重,初发皮损为面部者病情较轻。PM型的初发年龄较迟,为20-30岁,初发皮损为前臂、手背、耳际和前额等非特定部位。PPPD型家系和PM型家系都有汗孔角化病不同类型的共存现象。结论 汗孔角化病是一种具有不同表现度的常染色体显性遗传病,具有多种临床类型和不同的遗传基础,不同临床类型间既存在一致性也存在差异性,而且不同临床类     

掌跖及泛发性汗孔角化症一家系报道

报告我国首例掌跖及泛发性汗孔角化症一家系调查。先证者10岁时右手中指掌尺侧出现一油菜籽大小的圆形角化性丘疹，继后发现面部出现相似丘疹，且皮损逐渐扩大并泛发全身；组织病理检查可见角化不全柱，符合汗孔角化症；家系调查为5代共90人，结果患病26例，其中男性17例，女性9例，符合常染色体显性遗传特点。诊断为显性遗传性掌跖及泛发性汗孔角化症。对该病的临床特征、组织病理、遗传方式及鉴别诊断等进行了讨论。     

Progressive palmoplantar keratoderma:a pedigree study

报告1例进行性掌跖角化病及其家系调查结果.先证者男,17岁.掌跖角化性斑块15年.皮肤科检查见双掌、跖部弥漫性角化性斑块,逾越至手背、足背,形成条状角化性斑块,并特征性累及足跟.皮损组织病理检查示表皮棘层及颗粒层肥厚伴显著正角化过度.诊断:进行性掌跖角化病.该家系4代中有4例该病患者(男3例,女1例),属常染色体显性遗传.     

点状掌跖角化病研究进展

点状掌跖角化病是一种少见的常染色体显性遗传性皮肤病，随着国内外家系报道的不断增多，对该病的临床表现、发病机制等方面的研究已成为热点。综述点状掌跖角化病的流行病学、临床表现、鉴别诊断、定位研究和伴发疾病等方面的研究进展。     

点状掌跖角化病研究进展

点状掌跖角化病是一种少见的常染色体显性遗传性皮肤病,随着国内外家系报道的不断增多,对该病的临床表现、发病机制等方面的研究已成为热点。综述点状掌跖角化病的流行病学、临床表现、鉴别诊断、定位研究和伴发疾病等方面的研究进展。     

毛囊角化病1例及家系调查

毛囊角化病(keratosis follicularis)又称Darier 病,是一种少见的常染色体显性遗传性皮肤病[1],人群患病率约为数万分之一.临床表现为脂溢性部位(胸腹部、腋窝、头面部等)的角化性丘疹,有时伴掌跖损害.多于20 岁前发病.日晒、潮湿可加重病情.组织学特征为棘层和角质层中的角化不良细胞形成圆体和谷粒,棘层松解形成裂隙,角化过度伴角化不全[2].我院近期诊治一家系毛囊角化病2 例,现报告如下.     

角化性皮肤病

20090162 β-Catenin在角化性皮肤病与非黑素细胞性皮肤肿瘤中的表达;20090163点状掌跖角化病一家系;20090164一例表皮松解性掌跖角化病家系的角蛋白9基因突变检测研究;20090165副肿瘤性肢端角化病误诊1例     

角化性皮肤病

中国汉族人5家系40例点状掌跖角化病临床及遗传特点分析；遗传性掌跖角化病一家系；掌跖角化症并发牙周病；阿维A治疗多发性日光性角化病1例；日光性角化病的治疗（综述）；     

Identification of a locus for punctate palmoplantar keratodermas at chromosome 8q24.13-8q24.21

Punctate palmoplantar keratodermas (PPK) is a rare autosomal dominant cutaneous disorder characterized by numerous hyperkeratotic papules that are irregularly distributed on the palms and soles. The genetic basis for this disease is unknown. We performed a genome-wide search in two Chinese families with punctate PPK to map the chromosome location of the responsible gene. We identified a locus at chromosome 8q24.13-8q24.21 with a cumulative maximum two-point LOD score of 5.41 at markers D8S1793 and D8S1774 (at recombination fraction theta=0.00). Haplotype analysis indicated that the disease gene is located within 9.20 cM region between markers D8S1804 and D8S1720. It is the first locus identified for the punctate PPK. This study provides a map location for isolation of a disease gene-causing punctate PPK.     

47 patients in 14 families with the rare genodermatosis keratosis punctata palmoplantaris Buschke-Fischer-Brauer

We summarize the clinical data of 47 patients with the rare genodermatosis keratosis punctata palmoplantaris Buschke-Fischer-Brauer. The pedigrees of 14 German families were studied. In three families there was only one member affected, two or more affected members were found in the other families. These family pedigrees were consistent with autosomal dominant inheritance. Variable expression of the disease was noted in members within one family. Over pressure points punctate keratoses coalesced into hyperkeratotic plaques. There was palmoplantar hyperhidrosis in 3 families associated with keratosis. Continuous systemic retinoid treatment can clear symptoms. Future genetic classification on a molecular basis may reveal the existence of more than one entity of this clinically heterogeneous genodermatosis.     

A new family with the rare genodermatosis keratosis punctata palmoplantaris Buschke-Fischer-Brauer

We describe a new family with the rare genodermatosis keratosis punctata palmo-plantaris Buschke-Fischer-Brauer (keratoma disseminatum). In all, 3 family members in 3 generations were affected, a pattern consistent with autosomal dominant inheritance. Clinical symptoms started in the third decade with disseminated, small, round, hyperkeratotic papules on the palms and soles. Punctate keratoses coalesced into hyperkeratotic plaques on pressure points. Identification of additional families is necessary to permit definitive genetic classification of this genodermatosis.     

Refined localization of a punctate palmoplantar keratoderma gene to a 5.06-cM region at 15q22.2-15q22.31

BACKGROUND: Punctate palmoplantar keratoderma (PPK) is a rare autosomal dominant cutaneous disorder characterized by numerous hyperkeratotic papules distributed on the palms and soles. Two loci for punctate PPK were recently found to be located on 8q24.13-8q24.21 and 15q22-15q24. However, no genes for this disease have been identified to date. Objectives To refine the previously mapped regions and to identify the disease gene locus in a four-generation Chinese family with punctate PPK. METHODS: Genetic linkage analysis was carried out in this family using microsatellite markers on chromosomes 8q and 15q. Two-point linkage analysis was performed using Linkage programs version 5.10 and the haplotype was constructed using Cyrillic version 2.02 software. RESULTS: We failed to confirm our previous locus at 8q24.13-8q24.21, but significant evidence for linkage was observed in the region of 15q with a maximum two-point LOD score of 5.38 at D15S153 (theta = 0.00). Haplotype analysis localized the punctate PPK locus within the region defined by D15S651 and D15S988. This region overlaps by 5.06 cM with the previously reported punctate PPK region. CONCLUSIONS: This study refines a disease gene causing punctate PPK to a 5.06-cM interval at 15q22.2-15q22.31.     

点状掌跖角皮症家系报道1例

报道点状掌跖角皮症一家系共30名成员，其中患者8例（男性3例，女性5例），属于常染色体显性遗传。先证者为70岁男性农民，于10岁时掌跖部开始出现圆形或椭圆形的角质丘疹，大小不一，直径为0．2－0．5cm，色泽暗黄，质地坚硬，剥除角质丘疹后，局部留有小凹陷，无出血。该家系中其他患者的皮损同先证者类似。     

Punctate palmoplantar keratoderma and malignancy in a four-generation family

Summary We report a large kindred in which a punctate palmoplantar keratoderma (PPK) is associated with malignancy, including Hodgkin's disease, renal, breast, pancreatic and colonic adenocarcinomas. The family was traced through four generations, and over 520 individuals were identified, of whom 49 had punctate PPK. The punctate PPK appeared to be inherited as an autosomal dominant trait with variable penetrance. Ten of the 43 adults (23%) with punctate PPK developed malignancies, and five of these developed before the age of 50. Of the 271 unaffected individuals, six (2%) have developed malignancies, one prior to the age of 50. The association of keratoderma and malignancy is discussed.     

Epidermolytic palmoplantar keratoderma of Vörner: re-evaluation of Vörner's original family and identification of a novel keratin 9 mutation

In 1901, Hans V?rner observed a family with a diffuse non-transgredient palmoplantar keratoderma of autosomal dominant inheritance. Histopathologically, he found epidermolytic hyperkeratosis as a characteristic sign and diagnostic criterion of this disorder. We performed a follow-up study of the family originally seen by V?rner in 1901 with clinical, histopathological, and molecular investigations. Clinically, affected family members showed the typical diffuse keratoses over the entire surface of the palms and soles sharply bordered by red margins. A mycotic infection was additionally found in two patients examined. Histopathological investigations confirmed epidermolytic hyperkeratosis. Molecular studies revealed a novel mutation in keratin 9, N160I, in patients from the family. The mutation in the coil-1A domain is thought to have a dominant negative effect on the assembly of keratin intermediate filaments, explaining the dominant inheritance of the phenotype. These findings give further evidence that palmoplantar keratoderma of V?rner represents the same entity as palmoplantar keratoderma of Thost, which was recently re-evaluated in Thost's original family and shown to be caused by a similar mutation, R162 W, in the same segment of keratin 9.     

Palmoplantar keratodermas: clinical and genetic aspects

Palmoplantar keratodermas comprise a diverse group of acquired and hereditary disorders marked by excessive thickening of the epidermis of palms and soles. Early onset and positive family history suggest a genetic cause. While hereditary forms of palmoplantar keratoderma (PPK) may represent the sole or dominant clinical feature, they may also be associated with other ectodermal defects or extracutaneous manifestations. In recent years, much progress has been made in deciphering the genetic basis of PPK, which has led to the emergence of new disorders and syndromes. The elucidation of disease mechanisms has opened new avenues for specific therapies, increasingly sparking interest in this field. Given the high heterogeneity with respect to clinical features, genetic defects, and disease mechanisms, the classification of PPK is based on various criteria. These include extent of disease manifestations, morphology of palmoplantar skin involvement, inheritance patterns, and molecular pathogenesis. Though not always feasible, the clinical distinction of various PPK entities is based on fine‐tuned criteria or clues. Remarkably, apparently distinct disorders have been shown to be allelic, as they are caused by mutations in the same gene. By contrast, similar clinical pictures may result from mutations in different genes. Because of this complexity, mutation analysis is required to determine the precise type of PPK. The best‐defined entities are described in this review.     

Homozygosity at chromosome 8qter in individuals affected by mal de Meleda (Meleda disease) originating from the island of Meleda

BACKGROUND: The inherited palmoplantar keratodermas (PPKs) are a clinically heterogeneous group of disorders characterized by thickening of the skin of the palms and the soles. These diseases also exhibit genetic heterogeneity and many autosomal dominant and recessive forms have been described. Mal de Meleda (Meleda disease, MD) is an autosomal recessive form of PPK first described on the Dalmatian island of Meleda. A gene for MD has recently been assigned to the most telomeric portion of chromosome 8q using two large Algerian families. OBJECTIVES: To determine whether the same gene underlies the skin disease in Meleda islanders. METHODS: We have examined five affected individuals originating from the Dalmatian island itself for 8qter homozygosity. RESULTS: This region was found to be homozygous in all five affected individuals but in none of the 20 other unaffected family members examined. CONCLUSIONS: The current study confirms the localization of a gene for MD to 8qter using samples from the island of Meleda, highlighting the clinical and genetic homogeneity of this condition.