先天性小眼球合并视网膜脱离一例

先天性小眼球是一种先天性发育异常的眼科疾病,并伴有其它眼部畸形,该病遗传方式多样,可为常染色体显性遗传、常染色体隐性遗传及X连锁隐性遗传,本文对临床上的一例先天性小眼球病例作一分析报道。     

先天性白内障的分子遗传学研究进展

先天性白内障(congenital cataract)是指在孕期或胎儿期由于各种因素使晶状体发育受到影响,是儿童致盲的首要原因之一.先天性白内障有明显的临床异质性和遗传异质性,一般与晶体蛋白基因、缝隙连接蛋白基因、转录因子基因及其他基因突变有关,常见的遗传方式有常染色体显性遗传、常染色体隐性遗传和性染色体连锁遗传,其中以常染色体显性遗传最为常见.近几年先天性白内障的分子遗传学水平有了新的突破,此文就其研究进展进行综述.     

显性遗传病的发病机理

一般记录、讨论遗传病的出发点是采用一定的遗传模型,然后观察某种疾病在一个家系中的出现方式是符合那一种模型。到目前为止已经确定或推测了所谓正常特征的2,300个以上的基因位点。根据遗传特征的不同,对遗传病可作如下分类:常染色体显性遗传,常染色体隐性遗传、X连锁显性遗传、X连锁隐性遗传,Y连锁遗传。现已知先天性代谢异常症的突变基因大部分为纯合子,因而表现出酶的“缺陷”或“缺少”的隐性遗传病。换句话说,只要在2个等位基因当中有一个是正常基因的杂合子,就能维持正常生理机能而不发病。     

性连锁遗传病的产前诊断与优生

从遗传学角度分析,遗传病分基因改变与染色体畸变两种,基因改变的遗传病的遗传方式又可分为:常染色体显性遗传,常染色体隐性遗传,X—连锁显性遗传,X—连锁隐性遗传及多基因遗传等;染色体畸变可分为染色体结构畸变和数目改变。染色体畸变可以通过染色体检查直接观察到,对于基因的改变,虽然有了一些方法,还存在着很大的局限性,而有一些性连锁的遗传病的产前诊断,是可以比较容易地看到的。根据性连锁的遗传病的遗传方式,通过鉴定胎儿性别决定留取胎儿达到优生的目的。     

两兄弟患一新型肌营养不良:应用DNA探针分析提示为常染色体隐性遗传

常见的肌营养不良为X连锁的DMD,另一X连锁类型为BMD。应用DNA探针的连锁分析已证实DMD、BMD为位于Xp21的等位突变基因引起。第三种X连锁的肌营养不良为罕见的Emery-Dreifuss型(E-DMD),其特点为早期发生挛缩和心肌病变,该基因已被定位于Xq27-q28。另外有一种临床症状与DMD相似的儿童肌营养不良,为常染色体隐性遗传病。本文作者报导了一个两兄弟同时患有肌营养不良症的家系,其临床所见不能确定为常染色体隐性遗传或X连锁隐性遗传,并进行了RFLP连锁分析。     

328例非特异性精神发育迟滞的隐性基因分析

采用分离分析和血缘分析方法，对山东省遗传病调查中发现的３２８个父母双方均正常的中、重度非特异性精神发育迟滞（ＮＳＭＲ）家系进行了分析。结果表明，多发家庭先证者的平均近婚系数显著高于一般群体，分离比接近０．２５。提示隐性基因在中、重度ＮＳＭＲ发生中起一定作用。在重度ＮＳＭＲ，散发病例占４０．７％，Ｘ连锁隐性遗传占９．１２％，常染色体隐性遗传占５０．１８％。常染色体隐性基因位点数的最小估计值为２４，各位点的平均基因频率为０．００３５，携带者总频率为１７．５４％；在中度ＮＳＭＲ，散发病例占６１．５％，Ｘ连锁隐性遗传占１１．５３％，常染色体隐性遗传占２６．９７％，常染色体隐性基因位点数的最小估计值为１３２，各位点的平均基因频率为０．００２１，携带者总额率为５４．９５％。     

X性连锁视网膜色素变性遗传学研究进展

视网膜色素变性 (retinitis pigmentosa,RP)是一组具有遗传异质性的单基因遗传性视网膜疾病。分为常染色体显性、常染色体隐性和 X-性连锁三种遗传形式。本文就 X-性连锁视网膜色素变性 (XL RP)的遗传学研究进展予以综述。     

心脏病的遗传

本文论述了孟德尔式、染色体及多基因三种主要遗传学原则,列举有心脏病表现的遗传性综合征及介绍遗传咨询过程,以期帮助心脏病学家能在医学实践中运用遗传学的概念。孟德尔式遗传孟德尔式遗传包括常染色体显性遗传、常染色体隐性遗传及X连锁隐性遗传三个类型。常染色体显性遗传如果一个病人只需一个致病基因就可致     

X性连锁视同多膜色素变性遗传学研究进展

视网膜色素变性（retinitis pigmentosa,RP)是一组具有遗传异质性的单基因遗传性视网膜疾病。分为常染色体显性、常染色体隐性和X－性连锁三种遗传形式。本就X－性连锁视网膜色素变性（XLRP）的遗传学研究进展予以综述。     

先天性遗传性白内障的基因学研究进展

先天性白内障是儿童常见的致盲性疾病,发病机制多种多样。非同系的人群中,大部分遗传性白内障是外显率较高的常染色体显性遗传,但也有X连锁和常染色体隐性遗传存在。随着分子生物学技术的发展,已经明确了先天性白内障的十几个基因、几十个独立位点的突变。基因学研究有助于揭示早期白内障的发病机制,为晶状体的发育和生理学研究提供新的见解,有助于进一步了解遗传、环境和营养等因素对晶状体的作用方式;遗传白内障的致病基因可能是老年性白内障的致病因素之一。就遗传性白内障的基因学研究进展进行综述。     

Genetic heterogeneity of syndromic X-linked recessive microphthalmia-anophthalmia: is Lenz microphthalmia a single disorder?

Nonsyndromic congenital microphthalmia or anophthalmia is a heterogeneous malformation with autosomal dominant, autosomal recessive, and X-linked modes of inheritance. Lenz microphthalmia syndrome comprises microphthalmia with mental retardation, malformed ears, skeletal anomalies, and is inherited in an X-linked recessive pattern. Prior studies have shown linkage of both isolated (or nonsyndromic) anophthalmos (ANOP1, [MIM 301590]) and Lenz syndrome [MIM 309800] to Xq27-q28. Nonsyndromic colobomatous microphthalmia [MIM 300345] has been linked to Xp11.4-Xq11.1. We describe a five-generation African-American family with microphthalmia or anophthalmia, mental retardation, and urogenital anomalies, in an X-linked recessive inheritance pattern, consistent with Lenz syndrome. Initial linkage analysis with microsatellite markers excluded the region in Xq27-q28 previously reported as a candidate region for ANOP1 [MIM 301590]. An X-chromosome scan revealed linkage to a 10-cM region between markers DXS228 and DXS992 in Xp11.4-p21.2. Multipoint analysis gave a maximum LOD score of 2.46 at marker DXS993. These data show that X-linked recessive syndromic microphthalmia exhibits genetic heterogeneity. In addition, it suggests that Lenz microphthalmia syndrome, previously thought to be a single disorder, may represent an amalgam of two distinct disorders.     

Genetic heterogeneity of syndromic X‐linked recessive microphthalmia‐anophthalmia: Is Lenz microphthalmia a single disorder?

Nonsyndromic congenital microphthalmia or anophthalmia is a heterogeneous malformation with autosomal dominant, autosomal recessive, and X‐linked modes of inheritance. Lenz microphthalmia syndrome comprises microphthalmia with mental retardation, malformed ears, skeletal anomalies, and is inherited in an X‐linked recessive pattern. Prior studies have shown linkage of both isolated (or nonsyndromic) anophthalmos (ANOP1, [MIM 301590]) and Lenz syndrome [MIM 309800] to Xq27–q28. Nonsyndromic colobomatous microphthalmia [MIM 300345] has been linked to Xp11.4–Xq11.1. We describe a five‐generation African‐American family with microphthalmia or anophthalmia, mental retardation, and urogenital anomalies, in an X‐linked recessive inheritance pattern, consistent with Lenz syndrome. Initial linkage analysis with microsatellite markers excluded the region in Xq27–q28 previously reported as a candidate region for ANOP1 [MIM 301590]. An X‐chromosome scan revealed linkage to a 10‐cM region between markers DXS228 and DXS992 in Xp11.4–p21.2. Multipoint analysis gave a maximum LOD score of 2.46 at marker DXS993. These data show that X‐linked recessive syndromic microphthalmia exhibits genetic heterogeneity. In addition, it suggests that Lenz microphthalmia syndrome, previously thought to be a single disorder, may represent an amalgam of two distinct disorders. © 2002 Wiley‐Liss, Inc.     

Genetic mapping of a novel X-linked recessive colobomatous microphthalmia

Colobomatous microphthalmia is a common ocular malformation with a heterogeneous phenotype. The majority of cases without associated systemic abnormalities have an autosomal dominant inheritance pattern [McKusick, 1990: Mendelian inheritance in man]. A few isolated cases with autosomal recessive transmission have been described [Zlotogora et al., 1994: Am J Med Genet 49:261--262]. To our knowledge, no cases of X-linked colobomatous microphthalmia that are not a part of a syndrome or a multisystem disorder have been reported. In this study, we describe a genetic and clinical evaluation of a large pedigree in which colobomatous microphthalmia is segregating in an X-linked recessive fashion. Based on recombination breakpoint analysis, we have determined that the critical interval exists between markers DXS989 and DXS441, placing the disease locus on the proximal short arm or the proximal long arm of the X chromosome. Using linkage analysis, we obtained two-point lod scores of 2.71 at zero recombination with markers DXS1058, DXS6810, DXS1199, and DXS7132. Overlapping multipoint analysis established a broad maximum from marker DXS1068 to marker DXS7132, a region spanning approximately 28 cM. This study provides evidence for the presence of a new locus for colobomatous microphthalmia.     

Autosomal recessive colobomatous microphthalmia

Colobomatous microphthalmia was studied in multiple relatives of 5 families. In these families, the disorder was an autosomal recessive trait as opposed to the usual autosomal dominant form of the disorder. A relatively high incidence of this recessive allele is found in the Iranian Jewish community. © 1994 Wiley-Liss, Inc.     

The PDAC syndrome (pulmonary hypoplasia/agenesis, diaphragmatic hernia/eventration, anophthalmia/microphthalmia, and cardiac defect) (Spear syndrome, Matthew-Wood syndrome): report of eight cases including a living child and further evidence for autosomal recessive inheritance

The combination of pulmonary agenesis/dysgenesis/hypoplasia, microphthalmia/anophthalmia, and a diaphragmatic defect (agenesis or eventration) is a rare syndrome presumed to have an autosomal recessive mode of inheritance based on a report of affected siblings born to unaffected parents [Seller et al., 1996]. The condition is known as Spear syndrome and Matthew-Wood syndrome, although genetic heterogeneity cannot be ruled out. We report on eight patients with this condition including a living child, three sibs and three isolated cases. Most presented with fetal ultrasound findings of microphthalmia/anophthalmia, and diaphragmatic eventration/hernia and in five, cardiac abnormalities were also found. The earliest detection was at 20 weeks gestation. This is the second report of sibs affected with this condition, which supports an autosomal recessive mode of inheritance. We present the first and only reported living patient with this condition and expand the intrafamilial, interfamilial, and ethnic variability of this condition. We suggest changing the condition's name to PDAC to reflect the most important components of this condition.     

Dominant syndrome with isolated cryptophthalmos and ocular anomalies.

We report on a mother and daughter with nonsyndromal cryptophthalmos. Both patients have additional ocular anomalies, including microphthalmia, retinal dysplasia, and Peters anomaly. The periocular and lid changes seen in these individuals are distinct from those seen in typical cryptophthalmos. The apparent dominant mode of inheritance in this family distinguishes this condition from autosomal recessive isolated cryptophthalmos and from the Fraser or cryptophthalmos syndrome.     

Macrosomia, microphthalmia, ± cleft palate and early infant death: a new autosomal recessive syndrome

An Arab girl with macrosomia, severe microphthalmia and early infant death is reported. Four other sibs were similarly affected; three of them had median cleft palate. All five sibs showed respiratory infections in early life and died either unexpectedly or because of a documented overwhelming infection. Parental consanguinity and affected sibs of both sexes strongly suggest autosomal recessive inheritance in this apparently new syndrome.     

Syndrome of microcephaly, microphthalmia, cataracts, and intracranial calcification.

We present two sisters with microcephaly, developmental delay, marked microphthalmia, congenital cataracts, cerebral and cerebellar hypoplasia, and intracranial calcification. No evidence of intrauterine infection was found. There have been previous reports of microcephaly, intracranial calcification, and an intrauterine infection-like autosomal recessive condition, but the sibs in this report appear to represent a more severe form of such a condition or a previously undescribed entity.