Marie Unna遗传性少毛症一家系7例

遗传性少毛症(hereditary hypotrichosis)即先天性脱发症(congenital alopecia),临床罕见,有常染色体显性、隐性和性连锁三种遗传方式,Marie Unna遗传性少毛症(Marie Unna hereditary hypotrichosis, MUHH)属常染色体显性遗传,现将我们所见一家系报道如下.     

常染色体显性遗传性少毛症研究进展

常染色体显性遗传性少毛症是一组较少见的临床和遗传异质性较强的疾病,表现为出生时或出生后不久即出现头皮或身体其他部位的毛发稀疏甚至完全缺失。该病既可单独发病,也可以作为其他综合征的一项临床表型。根据遗传表型的不同,该病可分为单纯性遗传性少毛症、遗传性头皮单纯性少毛症、Marie Unna型遗传性少毛症及常染色体显性遗传性羊毛状发。该文针对单独发病的常染色体显性遗传性少毛症的遗传学研究进展作一综述。     

遗传性皮肤病与妊娠

遗传性皮肤病包括单基因遗传性皮肤病和多基因遗传性皮肤病。经典遗传性皮肤病即单基因遗传性皮肤病,其遗传方式包括常染色体显性遗传、常染色体隐性遗传、X连锁隐性遗传、X连锁显性遗传。经典遗传性皮肤病目前尚无有效治疗手段,预防遗传性皮肤病的主要措施是减少患病胎儿出生。文中在介绍遗传性皮肤病的分类基础上,探讨不同种类和不同遗传方式的遗传性皮肤病在妊娠时应采取的对策。     

遗传性皮肤松弛症的研究进展

遗传性皮肤松弛症是一种可累及全身多个富含弹性纤维组织器官的遗传性疾病.其临床表现为进行性皮肤松弛.该病有三种临床类型:常染色体显性遗传、常染色体隐性遗传和X连锁隐性遗传,致病基因分别为弹性蛋白基因,Fibulin5(FBLN5)基因,Fibulin4(FBLN4)基因和ATP7A基因.该病目前无有效的治疗方法,显性遗传型主要影响美容,预后较好,隐性遗传型预后较差.     

先天性角化不良研究新进展

先天性角化不良(DC)是一种罕见的遗传性皮肤病,其临床特征为皮肤色素沉着、甲营养不良、黏膜白斑和骨髓增生障碍。分子遗传学研究显示,本病存在遗传异质性,其遗传方式为X连锁隐性遗传、常染色体显性遗传和常染色体隐性遗传3种,目前发现前2种遗传类型的致病基因为DKC1和TERC。该病治疗比较棘手,目前尚无根治方法。     

q遗传性秃发／少毛症分子遗传学研究进展

遗传性秃发／少毛症是一组临床少见的遗传性脱发性疾病。近年确定多种遗传性秃发／少毛症的致病基因及其染色体定位,包括Marie—Unna型遗传性少毛症（U2HR,8p21．3）、常染色体显性遗传性单纯性少毛症（APCDDl,18p11．22;RPL21,13q12）、常染色体隐胜遗传性单纯性少毛症（DSG4,18q12．1;DSC3,18q21．1;LIPH,3q26—27;P2RY5,13q13—14;10q11．23—22．3;7p21．3-22-3）、常染色体隐陛遗传性羊毛状发（LIPH,3q26—27;P2RY5,13q13—14）、常染色体显性遗传性羊毛状发（KRT74,12q12—14）和毛囊性鱼鳞病一秃发一畏光综合征（MBTPS2,Xp22）。这些基因在毛囊发生和毛囊生长周期过程中具有重要的调控作用,各种致病性突变均可导致毛囊发生和生长异常,引起秃发／少毛症。     

遗传性秃发或少毛症研究进展

遗传性秃发或少毛症是皮肤科一组比较少见的疾病.根据临床类型不同其具有特征性的临床表现各异.该组疾病的遗传方式可表现为常染色体显性遗传、常染色体隐性遗传和X连锁显性或隐性遗传.在分子遗传学方面,已有多个致病基因位点和/或致病基因被确定,如8p21、6p21、18p11、16q22、18q12、3q26、1p21、Xq13、5q32等致病基因位点和HR、CDH3、CDSN、DSG4、LIPH、ATP7A等基因.     

Marie Unna遗传性稀毛症的遗传异质性

目的对中国汉族人Marie Unna遗传性稀毛症进行基因组精细定位,从而为进一步找到该病的致病基因奠定基础。方法用覆盖8p21的18个微卫星标记对2个家系进行局部基因组扫描,利用Linkage软件(5.10版)和Cyrillic软件(2.02版)进行连锁和单倍型分析。结果家系1在常染色体显性遗传模式、外显率为99.9％时,在8号染色体上的微卫星标记D8S298和D8S1725处获得LODS(连锁分数)为3.01(θ=0.00)；单倍型分析将其定位于D8S282～D8S1839之间的1.1 cM内。家系2的连锁分析排除与8p21连锁。结论 Marie Unna遗传性稀毛症存在遗传异质性。     

遗传性单纯性少毛症1例及SNRPE基因突变研究

目的:报告国内首例由SNRPE基因突变导致的常染色体显性遗传性单纯性少毛症(少毛症11型)1例,并对其家系进行基因突变研究。方法:抽取患儿及其父母外周血,提取血液基因组DNA,同时取100例健康汉族人基因组DNA样品作对照,采用PCR方法扩增APCDD1、RPL21、SNRPE、HR基因所有外显子及其侧翼序列,并对产物进行测序分析。结果:患儿SNRPE基因存在剪切位点杂合突变,c.144+4AC。患儿父母及100例健康对照均未发现该杂合突变。结论:SNRPE基因的杂合突变c.144+4AC可能为导致该遗传性单纯性少毛症家系的原因。     

无汗性外胚叶发育不全遗传类型及临床特点分析

目的 分析无汗性外胚叶发育不全 的遗传类型和临床特点。方法 采用临床检查和家系调查的方法，对5个无汗性外胚叶发育不全家系共计35例患者进行遗传类型和临床表现分析。结果 ① 家系Ⅰ、Ⅱ、Ⅳ和Ⅴ中所有患者合部为男性，女性只是隐性携带者，属X连锁隐性遗传 男子型；家系Ⅲ中的患者既有男性，又有女性，男女发病比例接近1：1，属常染色体显性遗传 。②在X连隐性遗传家系中，首次按照各家系的表现不同，又分为X连锁隐性遗传Ⅰ 型（眼睛型）和Ⅱ型（牙齿型），其中家系Ⅰ和家系Ⅳ属X连锁隐性遗传Ⅰ型，除表现为汗腺、毛囊缺陷外，还有先天低下，智力低于正常人；家系Ⅱ和家系Ⅴ属X连锁隐性遗传 Ⅱ型，除表现为汗腺、毛囊缺陷外，还有先天缺牙或牙齿发育不全，智力与同龄正常人相同，这也是中国汉族人无汗性外胚 叶发育不全患者与国外的不同之处。在常染色体显性遗传家系中，家系Ⅲ的患者均表现为无汗毛或汗毛稀少，身体部分无汗，无其它特殊体征。 ③X连锁隐性遗传患者的组织病理表现为毛囊、汗腺等皮肤附属器先天性, 缺失，而常染色体显性遗传患者的组织病理表现为汗腺发育不良，少于正常人，而毛囊先天性缺失。结论 无汗性外胚叶发育不全的遗传类型和临床表现真有多样性。     

A Sporadic Case of Congenital Hypotrichosis Simplex of the Scalp: Difficulties in Diagnosis and Classification

Hereditary hypotrichosis simplex of the scalp is a genotrichosis characterized by a hair defect limited to the scalp in the absence of other ectodermal or systemic abnormalities. Only large pedigrees consistent with autosomal dominant transmission have been described to date. In this article the clinical and scanning electron microscopy findings of a nonfamilial case of congenital scalp hypotrichosis simplex are reported. In some patients the diagnosis of sporadic hypotrichosis simplex of the scalp should be considered after ruling out all other possible causes of congenital and hereditary hypotrichosis.     

Marie-Unna hereditary hypotrichosis: case report and review of the literature

We present an 18-year-old girl with progressively worsening hair thinning and loss since puberty. Her clinical history, physical examination, and pathology results were consistent with Marie-Unna hereditary hypotrichosis, a rare cause of autosomal dominant hereditary hair loss. She had no family history of similar hair loss and represents the first report of a new case of Marie-Unna hereditary hypotrichosis within a previously unaffected family.     

Progressive patterned scalp hypotrichosis,with wiry hair,onycholysis, and intermittently associated cleft lip and palate: clinical and genetic distinction from Marie Unna

Marie Unna hereditary hypotrichosis has been described in over a dozen families since 1924. Features include scant or no eyebrows at birth, the development of firm wiry hair in the first few years of life followed by a progressive patterned scalp alopecia in the second or third decade. This is associated with generalized hypotrichosis of the body and the condition is nonsyndromic. We have identified a novel form of autosomal dominant ectodermal dysplasia that resembles Marie Unna hereditary hypotrichosis in a family of 23 members over four generations. Affected individuals have patterned hair loss and associated hair shaft dystrophy similar to that seen in Marie Unna hereditary hypotrichosis. It differs from Marie Unna hereditary hypotrichosis by an absence of signs of affectation at birth, relative sparing of body hair, distal onycholysis, and intermittent cosegregation with autosomal dominant cleft lip and palate. Linkage studies to the known Marie Unna locus at 8p21 near the Hairless gene were performed. Linkage analysis using markers D8S298, D8S560, D8S258, and D8S282 revealed significant exclusion of this locus (Z = -2.0 or lower) at theta = 0.1. This demonstrates that this novel ectodermal dysplasia is both phenotypically and genetically distinct from Marie Unna hereditary hypotrichosis.     

Alopezien und Hypotrichosen im Kindesalter

The monogenic inherited isolated alopecias comprise a group of clinically and genetically heterogeneous disorders with decreased or absent hair. Clinical classification of the isolated alopecias is based upon the onset of the disorder, the regions affected, and the structure of the hair shaft. Men and women are equally affected, and the mode of inheritance is autosomal dominant or autosomal recessive. Therapy does not exist for these rare forms of alopecia. However, molecular genetic diagnosis is possible for the identification of the genetic causes and for the specification of the recurrence risk. Since the identification of the keratin gene KRT86 as a cause of the so called monilethrix in 1997, mutations in eleven other genes have been identified for various isolated alopecias. These include other keratin genes for monilethrix, the HR gene for atrichia congenita, the genes CDSN, APCDD1 and SNRPE for the autosomal dominant form of hypotrichosis simplex, and the genes DSG4, LIPH and LPAR6 for the autosomal recessive forms of hypotrichosis as well as U2HR for hypotrichosis type Marie Unna. Molecular genetic and pathophysiological studies of these rare disorders of hair development have significantly contributed to our understanding of the basic mechanisms of hair loss as well as the physiological mechanisms of hair growth.     

Mutations in the P2RY5 gene underlie autosomal recessive hypotrichosis in 13 Pakistani families

Background  Autosomal recessive hypotrichosis is a rare genetic irreversible hair loss characterized by sparse scalp hair, sparse to absent eyebrows and eyelashes, and sparse axillary and body hair. Affected male individuals have normal beard hair.
Objectives  To search for pathogenic mutations in the human P2RY5 gene in Pakistani families with autosomal recessive hereditary hypotrichosis.
Methods  In the present report, 16 unrelated consanguineous Pakistani families having multiple affected individuals with autosomal recessive hypotrichosis were investigated. Linkage in these families was searched by genotyping microsatellite markers linked to autosomal recessive hypotrichosis loci LAH1, LAH2 and LAH3. Thirteen of the families showed linkage to the LAH3 locus on chromosome 13q14.11–q21.32. These families were then subjected to direct sequencing of the P2RY5 gene, which encodes a G protein-coupled receptor.
Results  Sequence analysis of the P2RY5 gene revealed two novel missense mutations (c.742A>T; p.N248Y and c.830C>T; p.L277P) in three families. Five previously described mutations including three missense (c.188A>T; p.D63V, c.436G>A; p.G146R, c.562A>T; p.I188F), one insertion (c.69insCATG; p.24insHfsX52) and one complex deletion (c.172–175delAACT; 177delG; p.N58–L59delinsCfsX88) were detected in the other 10 families.
Conclusions  Mutations revealed in the present study extend the body of evidence implicating the P2RY5 gene in the pathogenesis of human hereditary hair loss.     

Mutations in the CDSN gene cause peeling skin disease and hypotrichosis simplex of the scalp

Peeling skin disease is a rare genodermatosis characterized by superficial exfoliation or peeling of the skin. Peeling skin disease is caused by biallelic mutations in CDSN as an autosomal recessive trait. Monoallelic mutations in CDSN have also been described in an autosomal dominant inherited genodermatosis: hypotrichosis simplex of the scalp. This disease is characterized by progressive hair loss of the scalp with onset after early childhood. Clinical data were obtained from a patient with lifelong generalized skin peeling and both his parents. The patient's parents did not suffer from skin peeling, but the mother had a history of thin scalp hair since early childhood. Mutation analysis in the patient showed compound heterozygous mutations in exon 2 of CDSN, a nonsense mutation c.598C>T (p.[Gln200*]), previously associated with hypotrichosis simplex of the scalp, and a frame-shift mutation c.164_167dup (p.[Thr57Profs*6]), previously described in peeling skin disease. The p.(Gln200*) mutation was also found in the mother of the proband. Our study strengthens the previously established link between mutations in CDSN to peeling skin disease and hypotrichosis simplex of the scalp.     

More than one gene involved in monilethrix: intracellular but also extracellular players

Monilethrix, an autosomal dominant human hair disorder, is caused by mutations in three type II hair cortex keratins. Rare cases of the disease with non-vertical transmission have now been found to overlap with localized autosomal recessive hypotrichosis. The underlying gene, desmoglein 4 (DSG4), belongs to the desmosomal cadherin superfamily and is also expressed in the cortex of the hair follicle.     

Hypohidrotic Ectodermal Dysplasia: Argument Against an Autosomal Recessive Form Clinically Indistinguishable from X-Linked Hypohidrotic Ectodermal Dysplasia (Christ-Siemens-Touraine Syndrome)

Hypohidrotic ectodermal dysplasia (HED) is a well-described, X-linked recessive disorder characterized by hypohidrosis, hypodontia, and hypotrichosis in males. Reports of similarly affected females have suggested autosomal recessive inheritance in some families. The evidence for two clinically identical but genetically distinct disorders is not convincing, however. In two families with X-linked recessive inheritance of HED, the condition was severe in females. A critical review of previously reported cases of presumed autosomal recessive HED suggests that an autosomal recessive form of the condition identical to the X-linked HED may not exist. All sporadic instances of females with classic HED should be considered to be X-linked recessive, and counseling for X-linked recessive inheritance as well as autosomal recessive inheritance should be given.     

Hereditary hypotrichosis simplex of the scalp

A peculiar variety of hereditary hypotrichosis is described. The abnormality has affected a large family over the course of eight generations. This genealogy is the fullest so far known of hereditary hypotrichosis. The condition is a hypotrichosis limited to the scalp, which first manifests itself in the early school-years. Afterwards the loss of scalp hair gradually progresses to almost total alopecia. This terminal stage is reached between the ages of 20 and 25 years, and the condition affects males and females in a similar way. From the genetic point of view, the abnormality is transmitted with an autosomal dominant mode of inheritance with full penetrance.