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1.
The association of motor nerve conduction velocity (MNCV) to (1) duration of symptoms, (2) deep tendon reflex responses, (3) clinical muscle atrophy, and (4) ultrastructure of quadriceps muscle was studied in 18 patients with myotonia dystrophica of Steinert and nine normal controls. These patients had neither diabetes mellitus nor any other type of muscle dystrophy. Ultrastructural features of muscle fibers and intercellular spaces between atrophic fibers provided a basis for identifying degenerative changes and evaluating them semi-quantitatively. Our study indicates presence of an association between the pattern of muscle degeneration and both MNCV (correlation coefficients, gamma = +0.60) and duration of symptoms (gamma = -0.62), but not between MNCV and duration of symptoms (gamma = +0.28). Further analysis of the association between the degeneration of quadriceps and the MNCV of a distant peroneal nerve (which does not innervate quadriceps) suggested that the systemic nerve degeneration occurred in some groups of myotonia patients. Our study indicates that while in some patients the muscle degeneration may have been associated with the impairment of neurogenic elements, in others it occurred in the absence of any MNCV abnormality. Our findings favor the role of both neuropathic and myopathic factors in the muscle degeneration seen in myotonia dystrophica. 相似文献
2.
The Bcl-2 family in autoimmune and degenerative disorders 总被引:1,自引:0,他引:1
Delphine Mérino Philippe Bouillet 《Apoptosis : an international journal on programmed cell death》2009,14(4):570-583
Members of the Bcl-2 family are essential regulators of programmed cell death and thus play a major role in the development
and function of many tissues. The balance between pro-survival and pro-apoptotic members of the family decides whether a cell
will live or die. This mechanism allows organisms to get rid of cells that are no longer needed or have become dangerous.
Deregulation of apoptosis is a major contributing factor in the development of many diseases. A deeper understanding of how
the Bcl-2 family proteins orchestrate death in normal and pathologic conditions is thus relevant not only for disease etiology,
but also to try to prevent these various disorders. Experiments with transgenic and gene-ablated mice have helped elucidate
the function of the different members of the Bcl-2 family and their physiological roles. The present review highlights the
role of Bcl-2 family members in autoimmune and degenerative disorders, with a particular focus on the mouse models that have
been used to study their function. 相似文献
3.
J. M. Matsen M. H. Jones J. L. Sever E. D. Goldenberg M. R. Gilkeson K. M. Justus 《The Western journal of medicine》1970,112(3):14-19
A prospective study was initiated before the expected rubella epidemics in 1964 and 1965 in Los Angeles. Seventy-six families were evaluated by means of rubella complement fixing (cf) antibodies. The cf test, which has notable limitations, was chosen as a serologic test because it was possible to secure repeated samples of sera from all members of the families if venipuncture could be avoided.Definite evidence of clinical or serological rubella occurred in 13 of 399 persons enrolled in 1964, an attack rate of 3.3 percent. Four persons had clinical rubella only, five had clinical disease with seroconversion and four had seroconversion only. The ratio of apparent to unapparent disease was nine to four.There were four key families, each of which had more than one individual with definite clinical or serological evidence of rubella, suggesting that clustering of rubella cases does occur in families having an index case. In these families three types of intra-family spread were demonstrated: (1) all affected members had clinical disease, (2) all those affected had only inapparent disease, and (3) both apparent and inapparent disease in the same family. 相似文献
4.
Morales F Cuenca P del Valle G Vásquez M Brian R Sittenfeld M Johnson K Lin X Ashizawa T 《Revista de biología tropical》2008,56(1):1-11
Myotonia congenita is a muscular disease characterized by myotonia, hypertrophy, and stiffness. It is inherited as either autosomal dominant or recessive known as Thomsen and Becker diseases, respectively. Here we confirm the clinical diagnosis of a family diagnosed with a myotonic condition many years ago and report a new mutation in the CLCN1 gene. The clinical diagnosis was established using ocular, cardiac, neurological and electrophysiological tests and the molecular diagnosis was done by PCR, SSCP and sequencing of the CLCN1 gene. The proband and the other affected individuals exhibited proximal and distal muscle weakness but no hypertrophy or muscular pain was found. The myotatic reflexes were lessened and sensibility was normal. Electrical and clinical myotonia was found only in the sufferers. Slit lamp and electrocardiogram tests were normal. Two affected probands presented diminution of the sensitive conduction velocities and prolonged sensory distal latencies. The clinical spectrum for this family is in agreement with a clinical diagnosis of Becker myotonia. This was confirmed by molecular diagnosis where a new disease-causing mutation (Q412P) was found in the family and absent in 200 unaffected chromosomes. No latent myotonia was found in this family; therefore the ability to cause this subclinical sign might be intrinsic to each mutation. Implications of the structure-function-genotype relationship for this and other mutations are discussed. Adequate clinical diagnosis of a neuromuscular disorder would allow focusing the molecular studies toward the confirmation of the initial diagnosis, leading to a proper clinical management, genetic counseling and improving in the quality of life of the patients and relatives. 相似文献
5.
Guo H Zhuang XY Zhang AM Zhang W Yuan Y Guo L Yu D Liu J Yang DK Yao YG 《Biochimica et biophysica acta》2012,1822(10):1535-1543
Essential hypertension (EH, MIM 145500) is the most common cardiovascular disease and affects one-quarter of the world's adult population. Families with EH in a mode of maternal transmission have been occasionally observed in clinical settings and suggested an involvement of mitochondrial DNA (mtDNA) mutation. We aimed to characterize the role of mtDNA mutation in EH. We reported a large Han Chinese family with a maternally inherited EH and an extraordinarily high percentage of sudden death mainly in affected females. Analysis of the entire mtDNA genome of the proband identified a homoplasmic primary mutation m.14484T>C for Leber's hereditary optic neuropathy (LHON), along with several variants indicating haplogroup F1 status. Intriguingly, no maternal member in this family had LHON though they all harbored m.14484T>C. The arterial stiffness of the members carrying mutation m.14484T>C was significantly increased than that of non-maternal members without this mutation. No environmental factor (including age, sex, smoking, diabetes, hyperlipidemia) was correlated with the decreased aortic elastic properties observed in affected members. Mitochondrial respiration rate and membrane potential (ΔΨ(m)) were significantly reduced in lymphoblastoid cell lines established from affected members carrying m.14484T>C when compared to control cell lines (P<0.05). There was an elevation of reactive oxygen species and a compensatory increase of mitochondrial mass in mutant cell lines. Our results suggest that m.14484T>C causes EH under certain circumstance. This study provides a paradigm for diverse phenotypes of the primary LHON mutation and suggests for the necessity of routine cardiac evaluation in patients with the primary LHON mutation. 相似文献
6.
Von Hippel-Lindau disease, an autosomal dominant condition with complete penetrance, has been recognized in a large family that originated in Newfoundland but has some members who live in New Brunswick and Ontario. A collaborative investigation was begun in 1982 to document the number of affected members and the extent of their disease and to improve management of the disease. The condition has been documented in 38 members of the family, 28 living and 10 dead. The most common manifestations are retinal angioma (present in 60% of the gene carriers) and pheochromocytoma (present in 53%). Of the 28 living affected members 14 had been identified before the study began. Only 3 of the 14 patients in whom the disease was subsequently diagnosed presented with symptoms; in the remaining 11 the condition was detected by routine screening. Overall the mean age at the time of diagnosis was 23 years; in the 21 affected members of the fourth generation it was 18 years. The authors outline a regimen of regular screening for members at risk that has evolved as a result of their experience with this family. 相似文献
7.
R J Jorgenson J S Dowben S L Dowben 《Journal of craniofacial genetics and developmental biology》1987,7(4):403-412
A three generation family with hypohidrotic ectodermal dysplasia (ED) is presented. Attempts to categorize the disorder in the family as one of the recognized types of ED were unsuccessful. Affected members of the family have mild hypotrichosis, mild hypodontia, and variable degrees of hypohidrosis. Autosomal dominant inheritance is proposed. Scanning electron microscopy on the hair of members of the family is presented. While there is no specific pattern of defects of the hair of affected persons, the cuticular layer is defective and there are longitudinal grooves in the hair shafts. 相似文献
8.
Y. L. Ko J. J. Chen J. J. Cheng P. Kuan W. P. Lien T. K. Tang S. Y. Lin Y. C. Liou C. W. Wu C. C. Liew 《Human genetics》1996,97(5):585-590
Recent genotype-phenotype correlation studies in familial hypertrophic cardiomyopathy (FHC) have revealed that some mutations
in the β-myosin heavy chain (BMHC) gene may be associated with a high incidence of sudden death and a poor prognosis. Coexistence
of sudden death and end-stage heart failure in several families with FHC has recently being reported; however, the genetic
basis of such families has not been clearly demonstrated. A three-generation Chinese familial hypertrophic cardiomyopathy
(FHC) family (family HL1) with two cases of end-stage heart failure and three cases of sudden death was analyzed. The average
age of death in the affected members in this family was 34 years old. Genetic linkage analysis using polymorphisms in the
α- and β-myosin heavy chain genes revealed that FHC in this family is significantly linked to the BMHC gene without recombinations.
Single-strand conformation polymorphism analysis of exons 8, 9 and 13 to 23 in the BMHC gene showed a polymorphic band on
exon 14 that is in complete linkage with the disease status in this family. DNA sequencing analysis in the affected members
revealed an 453Arg→Cys mutation in the BMHC gene. To our knowledge this is the first reported mutation of FHC in Chinese.
Our data suggest that the 453Arg→Cys mutation is associated with a malignant clinical course in FHC due not only to sudden
death but also to end-stage heart failure.
Received: 6 July 1995 / Revised: 20 September 1995 相似文献
9.
Several members of a family living on the west coast of Scotland and on one of the islands off the coast had serious thrombotic disease. The plasma antithrombin III (ATIII) concentrations were measured by both functional and immunological assay in all available members of the family. Concentrations were 25% to 66% of normal in 12 people, including all seven with thrombotic disease. The inheritance pattern was characteristic of an autosomal dominant disorder. Thrombotic disease generally affected the leg, mesenteric, and axillary veins, although one man who had died before the study began had had severe arterial atheroma. In women the first thrombotic symptoms usually occurred during pregnancy. None of these patients have developed thrombotic symptoms until they were at least 18, so four younger members of the family who have ATIII deficiency but no thrombotic disease may eventually develop symptoms. 相似文献
10.
Anna T. vant Noordende Zoica Bakirtzief da Silva Pereira Pritha Biswas Mohammed Ilyas Vijay Krishnan Jayaram Parasa Pim Kuipers 《PLoS neglected tropical diseases》2021,15(4)
BackgroundLeprosy and leprosy-related stigma can have a major impact on psychosocial wellbeing of persons affected and their family members. Resilience is a process that incorporates many of the core skills and abilities which may enable people to address stigma and discrimination. The current study aimed to develop and pilot an intervention to strengthen individual and family resilience against leprosy-related discrimination.MethodologyWe used a quasi-experimental, before-after study design with a mixed methods approach. The 10-week family-based intervention was designed to strengthen the resilience of individuals and families by enhancing their protective abilities and capacity to overcome adversity. The study was conducted in two sites, urban areas in Telangana state, and in rural areas in Odisha state, India. Persons affected and their family members were included using purposive sampling. Two questionnaires were used pre-and post-intervention: the Connor-Davidson Resilience Scale (CD-RISC, maximum score 100, with high scores reflecting greater resilience) and the WHOQOL-BREF (maximum score of 130, with higher scores reflecting higher quality of life). In addition, semi-structured interviews were conducted post-intervention. Data were collected at baseline, a few weeks after completion of the intervention, and in the Odisha cohort again at six months after completion. Paired t-tests measured differences pre- and post- intervention. Qualitative data were thematically analysed.FindingsEighty participants across 20 families were included in the study (23 persons affected and 57 family members). We found a significant increase in CD-RISC scores for persons affected and family members from Odisha state (baseline 46.5, first follow-up 77.0, second follow-up 70.0), this improvement was maintained at six-month follow-up. There was no increase in CD-RISC scores post-intervention among participants from Telangana state. WHOQOL-BREF scores were significantly higher at follow-up for persons affected in both states, and for family members in Odisha state. No families dropped out of the study. In the qualitative feedback, all participants described drawing benefit from the programme. Participants especially appreciated the social dimensions of the intervention.ConclusionThis pilot study showed that the 10-week family-based intervention to strengthen resilience among persons affected by leprosy and their family members was feasible, and has the potential to improve resilience and quality of life. A large-scale efficacy trial is necessary to determine the effectiveness and long-term sustainability of the intervention. 相似文献
11.
目的:分析一家族性肥厚型心肌病的特点。方法:对我院就诊的一肥厚型心肌病大家系进行临床调查研究,分析其临床特点,绘制家系图谱。结果:该家系为连续四代遗传,家系成员共35例,患者11例,猝死3例,死亡2例。有1例患者房颤及脑梗塞,2例患者行永久性起搏器植入术,猝死年龄最小3岁,符合肥厚型心肌病高发病率、高猝死率、发病年龄早等特点。结论:家族性肥厚型心肌病详细的家系调查有助于了解疾病全貌,更好地揭示其遗传规律。 相似文献
12.
13.
Jou SB Lin HM Pan H Chiu YL Li SY Lee CC Hsiao KM 《Proceedings of the National Science Council, Republic of China. Part B, Life sciences》2001,25(1):40-44
Myotonic dystrophy (DM) is an inherited, autosomal dominant muscular disease which is primarily caused by a CTG trinucleotide expansion mutation on chromosome 19q13.3. The size of this trinucleotide repeat is related both to the age of onset and to the severity of the clinical manifestation. This disease is very rare in Taiwan, and clinical and genetic study on DM has not yet been documented in this area. Here, we present both clinical features and degrees of CTG expansion for a Taiwanese DM family. All of the DM patients examined in this family showed obvious clinical manifestations by age 30, which included facial and limb muscle weakness with atrophy, myotonia, and ptosis. In addition, individual DM members also exhibited variable phenotypes, which may reflect the complexity of the pathogenic mechanism. Because the collection of blood specimens was considered to be an invasive procedure, a genetic study on this DM family was performed using buccal cells. Our results confirmed that four members showing classic symptoms of DM had CTG repeat expansion in the DMI locus, and that one member with ptosis and minor muscle weakness in the right foot was a normal homozygote for CTG repeat. These data demonstrate that buccal cells can provide clear and reliable results, and thus, are suitable for a family study of DM. 相似文献
14.
Additional copies of the proteolipid protein gene causing Pelizaeus-Merzbacher disease arise by separate integration into the X chromosome
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Hodes ME Woodward K Spinner NB Emanuel BS Enrico-Simon A Kamholz J Stambolian D Zackai EH Pratt VM Thomas IT Crandall K Dlouhy SR Malcolm S 《American journal of human genetics》2000,67(1):14-22
The proteolipid protein gene (PLP) is normally present at chromosome Xq22. Mutations and duplications of this gene are associated with Pelizaeus-Merzbacher disease (PMD). Here we describe two new families in which males affected with PMD were found to have a copy of PLP on the short arm of the X chromosome, in addition to a normal copy on Xq22. In the first family, the extra copy was first detected by the presence of heterozygosity of the AhaII dimorphism within the PLP gene. The results of FISH analysis showed an additional copy of PLP in Xp22.1, although no chromosomal rearrangements could be detected by standard karyotype analysis. Another three affected males from the family had similar findings. In a second unrelated family with signs of PMD, cytogenetic analysis showed a pericentric inversion of the X chromosome. In the inv(X) carried by several affected family members, FISH showed PLP signals at Xp11.4 and Xq22. A third family has previously been reported, in which affected members had an extra copy of the PLP gene detected at Xq26 in a chromosome with an otherwise normal banding pattern. The identification of three separate families in which PLP is duplicated at a noncontiguous site suggests that such duplications could be a relatively common but previously undetected cause of genetic disorders. 相似文献
15.
Anna T. vant Noordende Moges Wubie Aycheh Tesfaye Tadesse Tanny Hagens Eva Haverkort Alice P. Schippers 《PLoS neglected tropical diseases》2021,15(2)
A key issue for persons with leprosy-, lymphatic filariasis- and podoconiosis-related disabilities is the life-long need to practice self-management routines. This is difficult to sustain without regular encouragement and support of others. Family-based support may be a sustainable and feasible strategy to practice self-management routines. This proof of concept study aimed to develop and pilot a family-based intervention to support prevention and self-management of leprosy, lymphatic filariasis and podoconiosis-related disabilities in Ethiopia.We used a quasi-experimental pre/post intervention study design with a mixed methods approach. The study population included persons affected by leprosy, lymphatic filariasis and podoconiosis and their family members. All persons affected had visible impairments due to their condition. We collected physical impairment outcomes, data on activity limitations, stigma and family quality of life using the SALSA scale (range 0–80), the SARI stigma scale (range 0–63) and the Beach Centre Family Quality of Life scale (range 0–125) and conducted in-depth interviews and focus group discussions. Quantitative data were analysed using paired t-tests, unequal variances t-tests, linear regression and binary logistic regression. Qualitative data were coded using open, inductive coding and content analysis.The family-based intervention consisted of self-management of disabilities, awareness raising and socio-economic empowerment. The intervention was delivered over several monthly group meetings over the course of several months. A total of 275 (100%) persons affected attended at least one session with a family member, and 215 (78%) attended at least three sessions. There was no significant improvement in eye and hand problems after the intervention. However, foot and leg impairments, number of acute attacks, lymphedema and shoe wearing all significantly improved at follow-up. In addition, family quality of life significantly improved from 67.4 at baseline to 89.9 at follow-up for family members and from 76.9 to 84.1 for persons affected (p<0.001). Stigma levels significantly decreased from 24.0 at baseline to 16.7 at follow-up (p<0.001). Activity levels improved, but not significantly.This proof of concept study showed that the family-based intervention had a positive effect on impairments and self-management of disabilities, family quality of life and stigma. We recommend a large-scale efficacy trial, using a randomised controlled trial and validated measurement tools, to determine its effectiveness and long-term sustainability. 相似文献
16.
Hao Guo Xin-Ying Zhuang A-Mei Zhang Wen Zhang Yong Yuan Li Guo Dandan Yu Juan Liu Da-Kuan Yang Yong-Gang Yao 《生物化学与生物物理学报:疾病的分子基础》2012,1822(10):1535-1543
Essential hypertension (EH, MIM 145500) is the most common cardiovascular disease and affects one-quarter of the world's adult population. Families with EH in a mode of maternal transmission have been occasionally observed in clinical settings and suggested an involvement of mitochondrial DNA (mtDNA) mutation. We aimed to characterize the role of mtDNA mutation in EH. We reported a large Han Chinese family with a maternally inherited EH and an extraordinarily high percentage of sudden death mainly in affected females. Analysis of the entire mtDNA genome of the proband identified a homoplasmic primary mutation m.14484T>C for Leber's hereditary optic neuropathy (LHON), along with several variants indicating haplogroup F1 status. Intriguingly, no maternal member in this family had LHON though they all harbored m.14484T>C. The arterial stiffness of the members carrying mutation m.14484T>C was significantly increased than that of non-maternal members without this mutation. No environmental factor (including age, sex, smoking, diabetes, hyperlipidemia) was correlated with the decreased aortic elastic properties observed in affected members. Mitochondrial respiration rate and membrane potential (ΔΨm) were significantly reduced in lymphoblastoid cell lines established from affected members carrying m.14484T>C when compared to control cell lines (P < 0.05). There was an elevation of reactive oxygen species and a compensatory increase of mitochondrial mass in mutant cell lines. Our results suggest that m.14484T>C causes EH under certain circumstance. This study provides a paradigm for diverse phenotypes of the primary LHON mutation and suggests for the necessity of routine cardiac evaluation in patients with the primary LHON mutation. 相似文献
17.
Glenn Gladys M. Daniel Lambert N. Choyke Peter Linehan W. Marston Oldfield Edward Gorin Michael B. Hosoe Shigeto Latif Farida Weiss Gary Walther McClellan Lerman Michael I. Zbar Berton 《Human genetics》1991,87(2):207-210
Summary As part of an attempt to locate the von Hippel-Lindau locus (VHL) on chromosome 3, we evaluated 41 families with von Hippel-Lindau disease from the United States and Canada. One large family was identified whose disease phenotype was distinct from typical VHL. The most common disease manifestation was pheochromocytoma occuring in 57% (27/47) of affected family members. Few (4/47) affected family members had symptomatic spinal or cerebellar hemangioblastomas; no affected family member had renal cell carcinoma (0/47) or pancreatic cysts (0/24). Previously, genetic analysis demonstrated that the disease manifestations in this family were linked to RAF1 and D3S18, markers shown to be linked to typical VHL. These results suggest that there are mutant alleles at the VHL locus associated with distinct tissue specificities. 相似文献
18.
Improved predictive testing for Huntington disease by using three linked DNA markers. 总被引:8,自引:6,他引:2
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M R Hayden C Robbins D Allard J Haines S Fox J Wasmuth M Fahy M Bloch 《American journal of human genetics》1988,43(5):689-694
Eighty-five persons at risk for Huntington disease (HD) have enrolled in a predictive-testing pilot program. Informativeness of the test has been determined for 41 of these candidates by using linked DNA probes. Nine (21.9%) of these persons have been excluded from the test as a result of the unavailability of DNA from crucial family relatives. Homozygosity for all of the three DNA markers (D4S10, D4S62, and D4S95) was not found in any affected parent. Only one (2%) of the 41 test candidates has had an uninformative result. Results have been given to 20 persons, of whom 12 (60%) received a decreased risk and eight (40%) received an increased risk of having inherited the mutant gene for HD. The combined use of three DNA markers significantly increases the informativeness of family structures such that some change in the estimation of genetic risk is now possible for approximately 75% of all persons who request predictive testing. 相似文献
19.
Summary Three families with at least three generations of family members affected with spino-cerebellar ataxia transmitted in a dominant fashion were studied. In each family every available member, above the lowest age at onset observed in that family, was subject to a thorough clinical investigation and blood was sampled for HLA,A,B and C-typing. In all three families the affected members had signs which were characteristic for cerebellar ataxia, without spasticity or dementia. In two families the mean age at onset was in accordance with the literature, viz. in the fourth and fifth decade, while in the third family mean age at onset was over 50 years. In the two pedigrees with the usual age at onset there was evidence of linkage between the disease and the HLA-system with a combined lod score of 1.499 at a recombination fraction of 0.05 for males. The third pedigree gave negative lod scores for linkage between HLA and the disease locus for both males and females but in this family also the high age at onset was indicative of genetic heterogeneity. 相似文献
20.
Huntington Disease without CAG Expansion: Phenocopies or Errors in Assignment? 总被引:7,自引:3,他引:4
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Susan E. Andrew Y. Paul Goldberg Berry Kremer Ferdinando Squitieri Jane Theilmann Jutta Zeisler Hkan Telenius Shelin Adam Elisabeth Almquist Maria Anvret Gerard Lucotte A. Jon Stoessl Giuseppe Campanella Michael R. Hayden 《American journal of human genetics》1994,54(5):852-863
Huntington disease (HD) has been shown to be associated with an expanded CAG repeat within a novel gene on 4p16.3 (IT15). A total of 30 of 1,022 affected persons (2.9% of our cohort) did not have an expanded CAG in the disease range. The reasons for not observing expansion in affected individuals are important for determining the sensitivity of using repeat length both for diagnosis of affected patients and for predictive testing programs and may have biological relevance for the understanding of the molecular mechanism underlying HD. Here we show that the majority (18) of the individuals with normal sized alleles represent misdiagnosis, sample mix-up, or clerical error. The remaining 12 patients represent possible phenocopies for HD. In at least four cases, family studies of these phenocopies excluded 4p16.3 as the region responsible for the phenotype. Mutations in the HD gene that are other than CAG expansion have not been excluded for the remaining eight cases; however, in as many as seven of these persons, retrospective review of these patients' clinical features identified characteristics not typical for HD. This study shows that on rare occasions mutations in other, as-yet-undefined genes can present with a clinical phenotype very similar to that of HD. 相似文献