不完全外显的遗传性痉挛性截瘫一家系临床与致病基因排除定位分析

目的 描述一个遗传了4代的不完全外显的遗传性痉挛性截瘫(hereditary spastic paraplegia,SPG)大家系的临床特征,并进行致病基因排除定位分析.方法 对SPG家系内11例患者的临床资料进行回顾性分析,并采用荧光多重PCR、毛细管凝胶电泳、Linkage软件包,选择对已定位常染色体显性遗传致病基因位点附近微卫星标记进行连锁分析.结果 该SPG家系的11例患者的发病年龄2～10岁,表现为缓慢进展的双下肢僵硬无力,四肢肌张力轻度增高,双上肢为主的腱反射亢进,剪刀步态和病理征阳性,无小便失禁或尿频、感觉障碍、眼震、痴呆等;遗传学分析该家系符合常染色体显性遗传,但外显不完全,连锁分析和突变分析发现该家系与已知的常染色体显性遗传SPG致病基因位点不连锁.结论 该SPG家系具有典型的"单纯型"痉挛性截瘫临床特点,发病年龄早,上肢体征较下肢明显,遗传学分析不支持该家系与已定位常染色体显性遗传位点相连锁,是一种新的SPG亚型.     

常染色体显性遗传腓骨肌萎缩症的分子遗传学进展

腓骨肌萎缩症(CMT)亦称遗传性运动感觉神经病,是最常见的遗传性周围神经病之一,多数呈常染色体显性遗传,也可呈常染色体隐性或X连锁遗传。根据临床和电生理特征,CMT一般分为两型:CMT1型(脱髓鞘型)和CMT2型(轴突型),另外还有介于二者之间的CMTDI型。CMT1和CMT2及CMTDI都可呈常染色体显性遗传,到目前为止已定位12型,其中9型的疾病基因已被克隆。本文主要对各型常染色体显性遗传CMT的分子遗传学进展加以综述。     

常染色体显性遗传腓骨肌萎缩症的分子遗传学进展

腓骨肌萎缩症（CMT）亦称遗传性运动感觉神经病，是最常见的遗传性周围神经病之一，多数呈常染色体显性遗传，也可呈常染色体隐性或X连锁遗传。根据临床和电生理特征，CMT一般分为两型：CMT1型（脱髓鞘型）和CMT2型（轴突型），另外还有介于二者之间的CMTDI型。CMT1和CMT2及CMTDI都可呈常染色体显性遗传，到目前为止已定位12型，其中9型的疾病基因已被克隆。本文主要对各型常染色体显性遗传CMT的分子遗传学进展加以综述。     

SPG4基因的遗传学研究

遗传性痉挛性截瘫(hereditary spastic paraplegia,HSP),又称为家族性Strümpell-Lorrain病,是一种具有临床及遗传高度异质性的神经系统遗传病,患病率为2/10万～9.6/10万,表现为缓慢进展的双下肢无力及痉挛性截瘫.根据遗传方式不同HSP可分为常染色体显性遗传、常染色体隐性遗传和X-连锁隐性遗传,以常染色体显性遗传最常见.目前已经发现40个HSP基因位点,已克隆19个疾病基因.其中spastin基因突变所致的遗传性痉挛性截瘫4型(spastic paraplegia-4,SPG4)约占常染色体显性遗传的HSP的40%.基因检测是诊断该病的金标准,有助于早期诊断、症状前诊断及产前诊断.动物模型的研究对揭示HSP的分子病理机制有重要作用,本文就SPG4基因的遗传学研究作一概述.     

遗传性痉挛性截瘫12例临床报告

目的研究遗传性痉挛性截瘫的临床表现和遗传特点。方法回顾性分析12例患者的临床资料。结果本组起病年龄为10～52岁,平均年龄22岁;35岁以下11例,35岁以上1例;单纯型9例,复杂型3例;3个家族有阳性家族史,共7例患者,散发病例5例。结论本组遗传性痉挛性截瘫患者多于青少年或青年发病,男性多于女性,单纯性较复杂型多见,遗传方式以常染色体显性遗传多见。     

新生儿大疱表皮松解症病例报告及综合临床分析

新生儿大疱表皮松解症（epidermolysisbullosa）是一组遗传性皮肤疾病,是常染色体显性或者隐性遗传,其特征为皮肤和粘膜损害,轻微机械性损伤,引起大小不等的疱疹,以水疱及血疱为主,是非炎症性皮肤病,Nikolsky征阳性或者阴性。根据本病的遗传方式,临床表现,病理特点,电镜检查等可分为4型：1.单纯型大疱表皮松解症[epider-molysisbullosasimplex（Koebner型）]是1965年由Passarg首次报道,属于常染色体显性遗传,发病率为1/5万属于轻型。又分为两种类型：①手足大疱表皮松解症（Cockanye）型;②疱疹样型大疱表皮松解症（Dowling-Meare型）较常见。2.显性遗传营养不良型大疱表皮松解症是常染色体显性遗传（AD）,基因定位于3p21。3.隐性遗传营养不良型大疱表皮松解症（Hallopeau-Siemens型）,是1952年由BOOK首次报道。Ⅳ型胶原纤维突变引起大庖性表皮松解症,致病基因定位于染色体11q11-q23发病率：0.3/10万。4.致死性大疱表皮松解症型又称交接性大疱松解症,是常染色体隐性遗传病。     

三姐弟的先天性成骨不全

根据流行病学和遗传学研究,1979年Sillence等提出至少存在四种不同的成骨不全综合征:具有兰色巩膜的常染色体显性遗传的成骨不全(I型);具有扭曲的股骨和串珠状肋骨的常染色体隐性遗传的成骨不全(Ⅱ型);具有正常巩膜的常染色体隐性遗传的进行性变形的成骨不全(Ⅲ型);具有正常巩膜的常染色体显性遗传的成骨不全(Ⅳ型)。这些疾病类型的主要临床和遗传特征列于表。然而有关成骨不全Ⅱ型的遗传方式还有争论。     

妊娠期抗IgA抗体

IgA缺乏的男女发病率相等,可以表现为常染色体隐性遗传,也可表现为常染色体显性遗传.由于这种缺陷由母体遗传给小儿的机会要大于父体,故不易单纯从遗传学的角度加以解释.本文提示非α-2基因在先天     

伴远端肌萎缩遗传性痉挛性截瘫的分子遗传学研究进展

遗传性痉挛性截瘫(hereditary spastic paraplegia,HSP or SPG)是一组具有高度临床和遗传异质性的神经系统变性疾病,以缓慢进展的双下肢痉挛性截瘫和无力为主要临床特点,病理特点为皮质脊髓束及后索的轴突纤维退行性变.根据是否伴有脊髓外损害,又可将HSP分为复杂型和单纯型.近年来发现越来越多的HSP伴有远端肌萎缩症状,其致病基因到目前为止已定位16型,其中13型已被克隆.随着越来越多的基因被克隆,本病的分子遗传学机制将逐渐被揭示.     

常染色体显性遗传视网膜色素变性的研究概况

视网膜色素变性是视网膜感光细胞和色素上皮细胞变性导致夜盲和进行性视野缺损的一类眼底遗传病。常染色体显性遗传视网膜色素变性占视网膜色素变性的 2 0 %～ 2 5 %,已克隆至少 11个常染色体显性遗传基因。本文就常染色体显性遗传视网膜色素变性临床分型、基因定位、克隆和治疗等方面研究进展作一综述     

On the variable expression of the Brachmann-de Lange syndrome

A mother of normal intelligence and her moderately mentally retarded son, both with the typical facial features of the Brachmann-de Lange syndrome, are reported. We discuss the variable expression of the Brachmann-de Lange syndrome by comparing the autosomal dominant cases with the sporadic or presumed autosomal recessive cases. The autosomal dominant cases show milder symptoms in general. In our opinion, a de novo autosomal dominant mutation causes the severe form of the syndrome, recurrence within sibships being explained by germline mosaicism. In all convincingly autosomal dominant cases we found that the mother is the transmitting parent, suggesting genomic imprinting.     

Possible autosomal-recessive ocular coloboma

Ocular coloboma as an isolated anomaly often is inherited as an autosomal dominant trait. Possible autosomal recessive inheritance is suggested by the presence of colobomatous malformations in a brother and sister whose parents have apparently normal eyes. Possible genetic heterogeneity of isolated ocular coloboma makes genetic counseling in sporadic cases difficult since cases may be due to autosomal dominant and autosomal recessive mutations and non-genetic causes.     

Confirmation of the Zechi-Ceide syndrome

Atretic cephaloceles associated with multiple congenital anomalies are known to follow either autosomal dominant or autosomal recessive patterns of inheritance. Zechi-Ceide syndrome (OMIM 612916) is an autosomal recessive disorder, characterized by an occipital atretic cephalocele, characteristic facial features, and large feet. Here we describe a patient with findings fitting Zechi-Ceide syndrome, in whom some of the manifestations were also present in his mother, indicating either autosomal dominant inheritance with variable expression, X-linked inheritance, or a manifesting carrier of an autosomal recessive inheritance.     

Autosomal dominant inheritance in familial angiolipomatosis

A patient with familial angiolipomatosis in whom an autosomal dominant mode of inheritance could be established is described. This patient also had coincidental autosomal dominant polycystic kidney disease.     

Dominant branchial cleft syndrome with characteristics of both branchio-oto-renal and branchio-oculo-facial syndrome

A father and son are described with an autosomal dominant branchial cleft syndrome resembling both the branchio-oto-renal and the branchio-oculo-facial syndrome. Both syndromes may represent variant expressions of the same autosomal dominant gene.     

Genetic heterogeneity in Noonan syndrome: evidence for an autosomal recessive form

Most Noonan syndrome (NS) families are compatible with autosomal dominant inheritance with predominance of maternal transmission. Sporadic patients can be explained by new autosomal dominant mutations. Here we report four Dutch NS patients, two male and two female, each with unaffected consanguineous parents. All four had a typical NS phenotype and presented with hypertrophic obstructive cardiomyopathy (HOCM) at birth. In two cases the HOCM improved, in one case it deteriorated, and in one case it remained constant over 12 years. These patients support the existence of an autosomal recessive form of NS in which HOCM is more frequent than in autosomal dominant NS.     

Melorheostosis may originate as a type 2 segmental manifestation of osteopoikilosis

Melorheostosis is a non-hereditary disorder involving the bones in a segmental pattern, whereas osteopoikilosis is a rather mild disseminated bone disorder inherited as an autosomal dominant trait. Interestingly, melorheostosis and osteopoikilosis may sometimes occur together. In analogy to various autosomal dominant skin disorders for which a type 2 segmental manifestation has been postulated, melorheostosis may be best explained in such cases as a type 2 segmental osteopoikilosis, resulting from early loss of the corresponding wild type allele at the gene locus of this autosomal dominant bone disorder.     

Chorio-retinal dysplasia, microcephaly and mental retardation. An autosomal dominant syndrome

A condition is described which is characterized by chorio-retinal dysplasia, microcephaly and mental retardation, transmitted in an autosomal dominant fashion with variable expressivity. It is suggested that this condition is a distinct autosomal dominant syndrome.     

Spino-cerebellar ataxia in Western Norway

The cerebellar ataxia of Marie (SCA) was investigated in Western Norway, a region with a population of 725,000, and with several isolated communities. Two modes of transmission were found: autosomal dominant SCA segregating in four families, and autosomal recessive SCA segregating in nine families. Within the second category, two distinct clinical types were observed. One exhibited ataxia with additional spinal involvement, including both upper and lower motor neuron affection and sensory disturbances. In some cases there were also ophthalmoplegias, dementia, epilepsy, and Parkinsonian signs. The other type exhibited mostly ataxic signs with little additional spinal involvement, but with dementia, epilepsy, and ophthalmoplegias in some cases, and occasionally hyperkinesia and optic nerve atrophy. The autosomal dominant SCA cases showed a varied spino-cerebellar symptomatology, but lacked ocular signs and had less mental disturbances than recessive SCA. Additionally, the disease course was more benign in autosomal dominant than in autosomal recessive SCA. The dominant form did not affect life expectancy, whereas autosomal recessive SCA considerably reduced the life span. In four families displaying autosomal dominant SCA, 32 persons were examined: 11 were affected, 10 had unspecific neuropathy (Un), and 11 were unaffected. In six families with autosomal recessive SCA of the spino-cerebellar type, 53 persons were examined, of whom 11 were affected, 14 had Un, and 28 were unaffected. In two families (the third has been described elsewhere) with autosomal recessive SCA of the cerebellar type, 57 persons were examined: 12 were affected, 19 had Un, and 26 were unaffected. In the diagnosis of Un, a score system was used to record all types of neurological signs. The scores were corrected for effects of age and sex, based on findings in a normal population. The estimated prevalence figures in the region investigated were: 3.2/100,000 for autosomal dominant, 1.8/100,000 for spino-cerebellar autosomal recessive, and 1.2/100,000 for cerebellar autosomal recessive SCA; the gene frequencies were 3.9.10^-5, 2.5.10^-3, and 4.8.10^-4, respectively. The distribution of Un in SCA families indicated different aetiologies. Ratios in the recessive SCA families were compatible with Un sometimes representing a heterozygous SCA manifestation. The prevalence in dominant SCA families fitted with a hypothesis that Un behaved here as a polygenic trait. Clinical Un differences also supported these contentions. Un polygenes are assumed to be important contributors to the inter- and intrafamilial variation of phenotypes in autosomal dominant SCA.     

Unilateral partial tibia defect with preaxial polydactyly,general micromelia,and trigonomacrocephaly with a note on “developmental resistance”

We report a boy with predominantly unilateral severe tibia defect with a high grade of preaxial polydactyly. Family history suggests the possibility of autosomal dominant inheritance with reduced penetrance and quite variable expressivity. The boy's phenotype and other previously reported examples of predominantly unilateral involvement in autosomal dominant and autosomal recessive limb mutations strongly suggest a hypothesis of developmental resistance in the uninvolved parts.