Familial cold urticaria

Familial cold urticaria (FCU) is a rare autosomal dominant condition, first described in 1940. ¹ The onset is in early life in all reported cases. Symptoms are triggered by generalized exposure to cold air, particularly in damp and windy weather. The cutaneous lesions consist of erythematous macules or plaques, urticarial lesions and sometimes petechiae. Associated fever, chills, joint pains, nausea, stiffness and swelling of the hands and feet frequently occur. The symptoms are variable, ranging from mild to incapacitating. The pathogenesis of FCU remains unknown. To our knowledge only 10 pedigrees have been published, seven from the USA and one each from Holland, France and South Africa. ^2-12 We wish to report another extensive pedigree after having had the opportunity to investigate one member of the family in detail. A short form of this pedigree has been published elsewhere. ¹³     

单纯型大疱性表皮松解症Dowling-Meara亚型基因突变检测

目的探讨单纯型大疱性表皮松解症Dowling-Meara亚型(EBS-DM)的遗传学发病机制。方法报告1例单纯型大疱性表皮松解症Dowling-Meara亚型(EBS-DM)的家系,选择该家系中2例患者、1名正常人及50名无血缘关系者,扩增外周血基因组DNA中编码角蛋白14(K14)和角蛋白5(K5)的所有外显子,PCR产物进行序列分析。结果在此EBS-DM家系患者中,位于K14第1外显子的125位密码子由CGC突变CAC,导致精氨酸由组氨酸替代(R125H),而家系中正常人及与家系无关的50例正常人无此突变。结论该EBS-DM家系患者的K14第1外显子存在R125H突变。     

MBTPS2 mutation in a British pedigree with keratosis follicularis spinulosa decalvans

Keratosis follicularis spinulosa decalvans (KFSD; OMIM 308800) is an X-linked disorder characterized by widespread hyperkeratotic follicular papules (including keratosis pilaris-like lesions), facial erythema, hypotrichosis and scarring alopecia. KFSD results from mutations in the MBTPS2 gene. Mutations in this gene also underlie ichthyosis follicularis, alopecia and photophobia syndrome. We report a British pedigree with KFSD resulting from the mutation p.Asn508Ser. This particular mutation has been reported in three other pedigrees with KFSD (Dutch, American, British) and is the only pathogenic mutation reported in this disorder to date. However, the same mutation has also been reported in a Chinese pedigree with IFAP syndrome, highlighting the clinical heterogeneity and overlapping molecular pathology of these two disorders.     

Two novel mutations of the ATP2C1 gene in Chinese patients with Hailey–Hailey disease

Hailey–Hailey disease (HHD; OMIM 169600) is an autosomal dominant blistering disease. Pathogenic mutations in ATP2C1 encoding the human secretory pathway Ca²⁺/Mn²⁺-ATPase protein 1 (hSPCA1) have been identified since 2000. The aim of this study was to report a Chinese pedigree and a sporadic case of HHD and to explore the genetic mutations. The Chinese pedigree and the sporadic case of typical HHD were subjected to mutation detection of ATP2C1. The 27 coding exons and their flanking sequences were amplified and sequenced. The heterozygous C to T transition at nucleotide 2753 in exon 26 and G to T transition at nucleotide 2090 in exon 21 of the ATP2C1 gene were identified in a pedigree and a sporadic case of HHD, respectively. The C2753T transition resulted in a novel nonsense mutation of glutamine codon (CAG) to a stop codon (TAG) at amino acid residue 865 (Q865X) and the G2090T transition resulted in a novel missense mutation of glycine condon (GGA) to Valine (GUA) at amino acid residue 645 (G645V) in hSPCA1. This study should be useful for genetic counseling and prenatal diagnosis for affected families and in expanding the repertoire of ATP2C1 mutations underlying HHD. This work was supported by grant from the Natural Science Foundation of China (30471564).     

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。     

Homozygous missense mutation in fibulin-5 in an Iranian autosomal recessive cutis laxa pedigree and associated haplotype

Cutis laxa is a rare group of inherited and acquired disorders characterized by loose and redundant skin with reduced elasticity. Mutations in the elastin coding gene have been shown to cause autosomal dominant cutis laxa in three families. A homozygous mutation in the fibulin-5 coding gene was discovered in a Turkish pedigree showing recessive inheritance, and a different mutation in this gene was found in the heterozygous state in a sporadic case of the disease. Here, we report the third case of a mutation in the fibulin-5 coding gene in a recessive Iranian cutis laxa pedigree. The mutation is the same as previously reported in the Turkish pedigree, further confirming that it is causative of disease. A haplotype consisting of seven intragenic sequence variations common to both pedigrees is described for the mutation-carrying fibulin-5 allele.     

先天性甲肥厚症Ⅰ型一家系调查

报告先天性甲肥厚症一家系,4代17人中有8人患病,8例患者均于出生后不久即有甲变色,继而甲增厚．2-4岁时出现掌跖角化,局部摩擦后可发生水疱和糜烂。部分患者有舌苔白腻,所有患者均未见胎生齿及脂囊瘤。先证者双肘膝关节毛囊角化性丘疹,足趾及跖部灶性胼胝样角化过度,20甲营养不良。该家系中有2例患者2岁时因突发急性呼吸困难抢救无效而死亡。     

斑驳病一家系调查及基因突变研究

目的 探讨中国汉族斑驳病一家系的临床特征和基因突变情况。方法 对该家系临床资料进行收集、整理、照相存档及临床遗传学特征分析,并绘制系谱图。提取家系成员和正常人对照者外周血基因组DNA,采用PCR及DNA直接测序的方法对该家系进行基因突变检测。结果 该家系成员共73人。根据典型的临床特征,先证者及其他患者共14例均确诊为斑驳病,遗传方式为常染色体显性遗传。家系中患者均存在KIT基因13号外显子第1900位ATGA插入（1900insATGA）,导致第634位密码子处出现移码突变,KIT蛋白多肽翻译提前终止于第641位密码子。家系其他成员及50例正常人对照者未发现此突变。该突变位点此前未见报道。结论 一种新的KIT基因突变（1900insATGA）可能是引起该斑驳病家系临床表型的原因。     

Epidermolytic palmoplantar keratoderma in a Hispanic kindred resulting from a mutation in the keratin 9 gene

Epidermolytic palmoplantar keratoderma (EPPK) is a localized keratinization disorder caused by mutations in the highly conserved coil 1A domain of the keratin 9 gene, KRT9. We present a Hispanic pedigree spanning three generations, with affected individuals in all generations. Using polymerase chain reaction amplification and direct sequencing we demonstrated a previously reported missense mutation in KRT9, which is expressed almost exclusively in the skin of palms and soles. The C-->T missense mutation R162W changes a basic amino acid (arginine) to a neutral amino acid (tryptophan). We describe this mutation in a Hispanic pedigree with EPPK for the first time, extending the finding of this mutation in other genetic backgrounds, and demonstrating the prevalence of this mutation in diverse populations.     

Mal de Meleda: a new geographical localization in Anatolia

BACKGROUND: Mal de Meleda (MDM) is an autosomal recessive form of palmoplantar keratoderma first described on the Dalmatian island of Meleda. MDM has been observed in many other countries so that the origin of the MDM gene may be elsewhere than in Meleda. OBJECTIVE: After identification of the first MDM patient during a medical visit, a study was planned to reveal other families with MDM in the K?prü?ay region in Anatolia. METHODS: The patient was interviewed with a questionnaire including a pedigree drawing. All the subsequent cases reported to be of MDM were visited for clinical examination and pedigree drawings. RESULTS: Thirty-nine patients, 8 families and 2 additional cases with MDM were identified in a 50-km(2) mountainous region in K?prü?ay canyon in Anatolia. The prevalent clinical features were nail involvement (80%), 'glove-and-sock' distribution of the keratoderma (60%), edema on the hands/feet (60%), conical tapering of the fingertips (60%) and hyperhidrosis on the palms and soles (50%). CONCLUSION: To our knowledge, this is the largest series reported. The relationship between the patients in Meleda and those in Anatolia awaits discovery by further researches that will be carried out with the collaboration of dermatology, genetics and medical history departments.     

A syndrome of keratosis palmo-plantaris congenita, pes planus, onychogryphosis, periodontosis, arachnodactyly and a peculiar acro-osteolysis

A family with a symptom complex of pes planus, onychogryphosis, palmoplantar hyperkeratosis and periodontosis is reported. A detailed pedigree is given and the mode of inheritance is suggested.     

Dowling-Meara亚型单纯型大疱性表皮松解症一家系的基因突变检测

目的：研究Dowling-Meara亚型单纯型大疱性表皮松解症（DM－EBS）一家系的基因突变。方法：采用了免疫组化、电镜、聚合酶链反应－异源双链分析和DNA测序方法。结果：免疫组化显示裂隙发生于致密层以上;电镜显示本病的基底细胞下出现裂隙,张力微丝减少;通过聚合酶链反应－异源双链分析检测到K14的基因突变,进而应用直接测序法确定了突变位点：K14的1A区N123R。结论：本DM－EBS家系存在K14的基因突变。     

Progressive symmetric erythrokeratoderma: report of a Chinese family

A large pedigree of progressive symmetric erythrokeratoderma is reported. The proband was a 22-year-old male with generalized asymptomatic lesions characterized by symmetrical well-demarcated erythematous hyperkeratotic plaques mainly distributed on the extremities. The proband's parents were also affected, and they were first cousins. Thus, a case of familial progressive symmetric erythrokeratoderma is described.     

Familial atrophia maculosa varioliformis cutis: case report and pedigree analysis

Atrophia maculosa varioliformis cutis (AVMC) was first described in 1918, as a rarely reported form of idiopathic macular atrophy on the cheeks. Nineteen patients have been reported in the past 86 years. Recently we diagnosed a 25-year-old woman as AMVC and investigated her family history. We collected the clinical data of the pedigree and presumed that AVMV is in a autosomal dominant inheritance.     

Both low‐dose arotinoid ethylester and acitretin are effective in the treatment of familial erythrokeratodermia variabilis

We previously reported a large Chinese pedigree of erythrokeratodermia variabilis (EKV). A unique feature was that some of the affected members experienced transitory pustules on the border of classic lesions. Here we prescribed oral arotinoid ethylester and acitretin to two of the affected members in the pedigree, at starting dosage of 0.03 mg/day for arotinoid ethylester and 30 mg/day for acitretin, maintenance dosage of 0.03 mg every other day and 20 mg/day, respectively. Both patients reached complete clearance of the lesions during the treatment period. Side effect was negligible for the case on arotinoid ethylester. The patient on acitretin experienced elevated level of serum triglyceride and alanine aminotransferase that restrained further use.     

痒疹样营养不良型大疱性表皮松解症1例及家系调查

报告1例痒疹样营养不良型大疱性表皮松解症,并进行了家系调查.先证者男,26岁.患者1岁左右时双踝部出现数个水疱,双胫前皮肤在外伤、搔抓后形成圆形或卵圆形丘疹、结节,米粒至花生米大,暗红色,质地较硬,部分皮损表面有痂壳.双足多个趾甲增厚或脱失.皮损组织病理检查:多处表皮下裂隙形成,真皮内散在较多的表皮样囊肿,并有少量淋巴细胞浸润.该家系共4代30名成员,14人患有本病(男9例,女5例),属常染色体显性遗传.     

Rothmund-Thomson综合征2例及家系调查

报告2例Rothmund Thomson综合征病例,为表兄弟,分别3岁5个月和2岁8个月。他们的母亲是姐妹关系。2个病例都是在出生后的3-4个月时发病,主要表现为面部的皮肤异色症及身材稍矮小,智力和发育仍属正常。包括两病例在内,整个家系中在2-5代共有10人发病,全是男性患者。本家系的遗传方式与通常认为的常染色体遗传方式不符,而与性连锁隐性遗传较为吻合,该综合征是否也存在着多种遗传方式值得进一步探讨。     

Whole exome sequencing identified two point mutations of COL7A1 and FLG in a Chinese family with dystrophic epidermolysis bullous pruriginosa and ichthyosis vulgaris

We report a 21‐year‐old man with recurrent bullous eruptions and severe itching on the lower legs and feet since 5 years of age. Dry, dirty brown, tile‐like scales covered his lower legs with dystrophic toenails. Nodular prurigo‐like lesions, scarring papules and milia remitted after the bullous eruptions. His father and another two family members had similar but mild presentations with recurrent bullae on the lower legs. Whole exome sequencing detected the heterozygous variants of COL7A1 c.6698G>A and FLG c.7249C>T in this pedigree. COL7A1 c.6698G>A was reported in bullous dermolysis of the newborn and FLG c.7249C>T was reported in ichthyosis vulgaris. Thus, the diagnosis of dystrophic epidermolysis bullosa pruriginosa associated with ichthyosis vulgaris was made.     

表型差异的Brooke-spiegler综合征一家系基因突变检测研究

目的分析报道首例中国汉族B rooke-sp iegler综合征(BSS)家系中的圆柱瘤(CYLD)基因突变。方法收集家系资料并采集家系成员血样,从外周血中提取全基因组DNA,利用PCR反应扩增整个CYLD基因的编码序列,并对扩增产物进行直接测序分析。同时总结了PubM ed上2000年以来所报道的所有CYLD基因突变。结果迄今为止,共报道了33个CYLD基因的突变,笔者检测到一个过去曾报道与家族性圆柱瘤(FC)发生相关的无义突变2272C>T(R758X)。结论CYLD基因型与表型之间无一致关联性,报道的该突变可以导致中国汉族人BSS的发生。     

A Chinese pedigree of lymphoedema–distichiasis syndrome with a novel mutation in the FOXC2 gene

Lymphoedema–distichiasis syndrome (LDS) is a syndromic form of primary lymphoedema associated with double rows of eyelashes (distichiasis). Mutations in the FOXC2 gene were reported to be associated with this syndrome. In this study, we identified in a Chinese LDS pedigree a novel FOXC2 gene mutation, C.370C>T, leading to p.Leu124Phe. The novel mutation is not a common polymorphism, but is co‐inherited with the disease.