摘要:

Retinitis pigmentosa (RP) is an hereditary degenerative disease of the retina and a major cause of visual impairment, prevalence estimates ranging from 1 in 3000 to 1 in 7000. The condition may segregate as an autosomal dominant, autosomal recessive or an X‐linked recessive trait and it may also occur on a sporadic basis in up to 50% of cases. In the autosomal dominant form, close linkage to the DNA marker C17 (D3S47) was recently established in a large family of Irish origin displaying early‐onset disease (McWilliam et al. 1989), multipoint analysis indicating the gene for rhodopsin as a likely candidate (Farrar et al. 1990). In that gene, a C→A transversion in codon 23, resulting in a proline→histidine substitution has now been identified in 17 of 148 unrelated ADRP patients in the United States (Dryja et al. 1990). This mutation is absent however in the original Irish pedigree (it is also absent in 21 other dominant Irish pedigrees, representing approximately 70% of the estimated ADRP population) indicating that another mutation, either in rhodopsin itself, or in a gene very closely linked to rhodopsin is responsible for the disease in that family. Analysis of other dominant pedigrees using the C17 and/or rhodopsin probes has indicated either tight linkage (Bhattacharya, Personal Communication), looser linkage, possibly indicative of a second locus on 3q (Olsson et al. 1990) or no linkage (Farrar et al. 1990, Blanton et al. 1990, Inglehearn et al. 1990). Extensive genetic heterogeneity thus exists in the autosomal dominant form of this disease, and in the light of these new observations, earlier tentative evidence for linkage of ADRP to the Rhesus locus on chromosome I will be re‐evaluated. A locus for type II Usher syndrome (classical RP combined with congenital pedial deafness, and normal vestibular function) has now been established on the long arm of chromosome 1 (Kimberling et al. 1990). Type I Usher families, in which hearing loss is more profound and vestibular function absent, do not segregate with the same chromosome 1q markers, indicating the existence of another, as yet unlocated gene. In the X‐linked form of the disease, two genes, XLRP2 and XLRP3, have been located on the proximal short arm of the X chromosome using a combination of physical and linkage mapping techniques, and there is some evidence to suggest a possible third locus more distally located. Advances thus being made, in the localization, isolation and characterization of RP‐causing genes, are likely radically to extend our knowledge of the molecular pathology of this prevalent group of conditions over the n

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1990.tb03541.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Appropriate counselling and clinical management of the pregnant woman with a mosaic amniotic fluid cell karyotype are difficult. The majority of the data on mosaicism and pseudomosaicism are derived from studies employing the flask technique for the analysis of amniotic fluid cell cultures. Since the majority of laboratories now utilize thein‐situtechnique, such data may not be relevant when analyzing results from thein‐situcolony technique. We reviewed the incidence of mosaicism in 6339 amniotic fluid samples using thein‐situtechnique. Data are presented on the types of aberrations and clinical outcomes. A classification of mosaicism is presented that distinguishes mosaicism of clinical importance from that which is obviously of extrafetal origin or artifactual. This approach clarifies the significance of mosaic states detected by thein‐situcolony technique and provides a rational foundation for genetic counselling and for planning clinical interv

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1990.tb03542.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

We have performed a reinvestigation of a family with a presumably autosomal recessive form of pseudoinflammatory dystrophy, which we have followed for 25 years. The symptoms in this family are subretinal haemorrhages appearing at age 13–40 years in the central fundus, resulting in glial cicatrication in the outer retinal layers, progressive myopia and profound choroidal atrophy in the advanced stages of the disease. During the follow‐up study, a new affected subject was found in the younger generation, and two collateral cases, who had earlier been considered as probably affected subjects, were now considered to have other fundus affections. The new case is the daughter of an affected female. The possibilities of an autosomal dominant mode of inheritance or pseudodominance are discussed. Extended genealogical studies showed that the parents of all the affected subjects, with the exception of the new case, have their origin in an area which was isolated until recently and have several common ancestors within the last 8–10 generations. Recessive inheritance also logically explains the appearance of the disease in so few other members in the vertical line of the family. To this fundus dystrophy, the rule of Lenz seems to apply: If more or less the same phenotype can be caused by both a recessive and a dominant gene, the phenotype caused by the recessive gene is generally manifested earlier and by more severe sym

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1990.tb03543.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

The annual prevalence rates of ten selected informative morphogenetic variants (IMVs) were studied in 31 194 newborn infants over a period of 8 years (1980–1987). Two of them (preauricular sinus and ocular hypertelorism) revealed a highly significant decrease by logistic regression analysis. The other eight presented a stable pattern or small fluctuations which did not reach statistical significance. These data may serve as valuable baseline rates for monitoring IMVs in a specific newborn population. Their potential informative value as indicators of altered morphogenesis and their power for monitoring programs of environmental teratogenicity should be carefully verifie

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1990.tb03544.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Using Southern hybridization with the DNA probe pY3.4, we were not able to detect fetal DNA in blood of 36 pregnant women carrying male fetuses. Gestational ages ranged from 8–40 weeks of pregnancy. Using the same DNA probe, we were able to detect the male‐specific signal in experimental dilution series down to 1/5000 on autoradiograms. We conclude that the ratio of fetal DNA in maternal circulation, in contrast to previous estimations, must be lower than 1/5

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1990.tb03545.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Various authors have allocated a diagnosis of tricho‐dento‐osseous syndrome to cases originally reported as amelogenesis imperfecta (hypomaturation‐hypoplasia type) with taurodontism. The resulting confusion has prompted this critical review of the literature, and further information has been obtained from the authors concerned. Criteria for diagnosis of the two conditions are pro

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1990.tb03546.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

We have conducted investigations on members of three families with increased predisposition to cancer which appears to be inherited as an autosomal dominant trait. The aim of our studies overall is to provide markers for the mutant genes involved, so that gene carriers may be monitored closely for signs of malignant disease. This paper reports on studies of chromosome breakage in lymphocytes from affected and at‐risk family members and control subjects. No increase in spontaneous chromosome breakage was observed in family members compared with controls. An increased sensitivity to chromosome damage induced by the alkylating agent, N‐methyl‐N1‐nitro‐N‐nitrosoguanidine (MNNG), was observed in three members from two families; one person was affected, the others at risk. These families included cases of osteosarcoma, in addition to various types of cancer of epithelial origin. Two members (one affected, one at‐risk) of a third family showed increased sensitivity to the radio‐mimetic agent, bleomycin. This family appeared to represent the cancer family syndrome. Whilst not conclusive at present, our results appear to justify investigation of members of cancer families with respect to sensitivity to chromosome

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1990.tb03547.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

A large New England family with autosomal dominant familial spastic paraplegia is described. In a pedigree of 173 individuals, 71 affected individuals are identified. Seventeen cases examined by the authors are described with regard to the natural history of FSP in this family. A staging system for following progress and planning interventions is proposed. Three illustrative cases are presented. In this family, FSP is found to have a homogeneous clinical course with nearly complete penetrance. Onset occurs at or before 3 years of age with involvement limited to the lower extremities. After the initial onset, no significant progression was noted. Early aggressive habilitative care may result in more functional ambulation.

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1990.tb03548.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Two patients with oro‐facio‐digital syndrome type II (OFD‐II, Mohr syndrome) with associated cerebellar atrophy are described. Three other cases of the Mohr syndrome with cerebellar abnormalities are cited from the literature. Cerebellar involvement seems to be a clinical feature of this syndrome. Unfortunately, there is a lack of CNS reports for many of the previously described patients. In all cases with this entity, careful neurological and radiological examinations of the cerebellum are recomm

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1990.tb03549.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

The authors report a patient affected with mental retardation, dysarthria, bilateral testicular hypoplasia and extensive ulcers of the lower limbs. Clinical study and laboratory tests revealed 48,XXYY syndrome. The authors confirm the importance of differential diagnosis from Klinefelter syndrome, illustrating the parameters and the pathology of both syndromes. They discuss the hypotheses concerning the pathogenesis of the ulcerations, and stress the importance of clinical and genetic characterization, leading to a differentiated prognosis of social capacity and prospect of working.

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1990.tb03550.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY