Intelligence impairment, personality features and psychopathology disturbances in a family affected with CADASIL

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a small-vessel disease of the brain that is characterized by headache, recurring lacunar strokes, mood changes and progressive cognitive deterioration. The disease is transmitted with an autosomal dominant pattern and usually starts during midadulthood (at 30-50 years of age). Cognitive deficits in patients with CADASIL develop slowly. The dementia causes frontal-like symptoms and it typically develops after a history of recurrent stroke. We describe three patients from one Spanish family affected by this disease. All three cases underwent comprehensive clinical and neuropsychological examination, and were monitored for seven years. The results obtained in this study describe a) a significant loss of the intelligence quotient (IQ) and noticeable damage to abstract ability (g factor), b) mood and psychopathological disturbances (major depression and dysthymia), and c) a personality with neurotic features.     

家族性高胆固醇血症基因治疗的思考

家族性高胆固醇血症是最典型的常染色体显性遗传性疾病,是早发冠心痛的主要病因。随着目前人类基因组学的研究进展,基因治疗有望解决患者遗传基因缺陷,从根本上治疗家族性高胆固醇血症。期待在不久的将来,当人类娴熟的应用基因治疗技术时可以从根本上治愈多种基因相关疾病。推动人类医疗事业的巨大发展。     

Maternal Uniparental Isodisomy Causing Autosomal Recessive GM1 Gangliosidosis: A Clinical Report

Uniparental disomy is a genetic cause of disease that may result in the inheritance of an autosomal recessive condition. A child with developmental delay and hypotonia was seen and found to have severely abnormal myelination. Lysosomal enzyme testing identified an isolated deficiency of beta-galactosidase. Subsequently, homozygous missense mutations in the galactosidase, beta 1 (GLB1) gene on chromosome 3 were found. Parental testing confirmed inheritance of two copies of the same mutated maternal GLB1 gene, and no paternal copy. SNP analysis was also done to confirm paternity. The patient was ultimately diagnosed with autosomal recessive GM1 gangliosidosis caused by maternal uniparental isodisomy. We provide a review of this patient and others in which uniparental disomy (UPD) of a non-imprinted chromosome unexpectedly caused an autosomal recessive condition. This is the first case of GM1 gangliosidosis reported in the literature to have been caused by UPD. It is important for genetic counselors and other health care providers to be aware of the possibility of autosomal recessive disease caused by UPD. UPD as a cause of autosomal recessive disease drastically changes the recurrence risk for families, and discussions surrounding UPD can be complex. Working with families to understand UPD when it occurs requires a secure and trusting counselor-family relationship.     

Concomitant neuropsychiatric symptoms in a case of Ehlers-Danlos syndrome

The case of a 15-year-old boy with Ehlers-Danlos-Syndrome (EDS) is described. Clinically the symptoms of considerable hyperextension of joints, abnormal extensibility of skin, moderate bleeding tendencies and slight vulnerability of the skin, deformity of the thorax are corresponding with type I of EDS. Ocular symptoms are missing. Histologically the picture is that of mitis type resp. type II of EDS. An autosomal dominant inheritance is to be supposed. Psychically an imbecillity likely as a result of perinatally acquired brain damage, and an autistic syndrome of broken home situation are present. Differential diagnosis and genetic significance of EDS are discussed.     

Is synaesthesia an X-linked dominant trait with lethality in males?

In previous research the inheritance patterns of synaesthesia (eg experiencing colours from graphemes) has been studied and it was concluded that synaesthesia is most likely to be the outcome of a single gene passed on the X chromosome in a dominant fashion. In addition, it has been reported that the female-male ratio of synaesthetes is as high as 6:1 and the families of synaesthetes contain more female than male members. This raises the possibility that the gene may be associated with lethality in males. In this study we replicate and extend previous research by investigating the female-male ratio and inheritance patterns in a large sample of synaesthetic families (N = 85). We were able to verify the authenticity of grapheme-colour associates in at least one proband from each family using internal consistency. As before, our results show a female-male bias and are broadly consistent with an X-linked dominant mode of inheritance. However, there was no evidence of male lethality (eg synaesthetes are just as likely to give birth to sons as to daughters). Moreover, our female-male ratio of synaesthetes within families was 2:1--considerably lower than previous estimates. We speculate that men may be more reluctant to disclose synaesthesia than women (indeed, our female-male ratio based on self-referral was 3.7: 1). Finally, we discuss how the genotype may give rise to the phenotype in terms of changes in synaptogenesis or plasticity extending into childhood, to be subsequently shaped by the environment.     

Muscle biopsy--sampling and preparation of muscle fiber bundles

Biopsy pathology of muscle will be useful in the diagnoses of neuromuscular diseases. Techniques used for muscle biopsy provide muscle tissue in order to obtain high quality of histological and ultrastructural preparations and tissue for biochemical investigations. Therefore muscle should be obtained by open biopsy fulfilling anatomical conditions. Experiences received in about 500 open biopsies are reported.     

Evaluation of arm dominance by using the mechanomyographic signal

The authors collected and compared mechanomyo-graphic (MMG) signal behavior from the biceps brachii of left and right arms of right-handed men (n = 19) and women (n = 20) who performed isometric contractions at 5 contraction levels. Mean frequency (MF) and RMS values were calculated from the MMG signals that arose from lateral oscillations of muscle fibers. Across genders and arms, RMS values increased with contraction level and MF values decreased with increase in muscle contraction. The authors found no significant difference in those parameters between dominant and nondominant arms. Therefore, summation of muscle twitches obtained from the MMG signal collected in biceps brachii muscle does not reveal any difference between dominant and nondominant arms.     

Bayesian Risk Assessment in Genetic Testing for Autosomal Dominant Disorders with Age-Dependent Penetrance

Risk assessment is an essential component of genetic counseling and testing, and the accuracy of risk assessment is critical for decision making by consultands. However, it has been shown that genetic risk calculations may have high error rates in practice. Risk calculations for autosomal dominant disorders are frequently complicated by age-dependent penetrance and sensitivities of less than 100% in genetic testing. We provide methods of risk calculation for prototypical pedigrees of a family at risk for an autosomal dominant disorder with age-dependent penetrance. Our risk calculations include scenarios in which the sensitivity of genetic testing is less than 100%, and in which the sensitivity of genetic testing varies for different family members at risk. Our Bayesian methods permit autosomal dominant disease probabilities to be calculated accurately, taking into account all relevant information. Our methods are particularly useful for hereditary cancer syndromes, in which genetic testing can seldom achieve 100% sensitivity. Our methods can be applied to many different scenarios, including those where the sensitivity of genetic testing varies for different family members at risk. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.     

Behavior genetic analysis of Water-T-Maze learning in inbred strains of mice,their hybrids,and selected second generation crosses

Summary The Water-T-Maze was used to investigate the genetically determined apparatus-dependent behavior of mice. Special importance was attached to the mode of inheritance involved. For this purpose we used NMRI, C3H/HeJ, Balb/c, Balb/cN, DBA/2, C57Bl/6 inbred mouse strains, together with their offspring and the F₂-hybrids of C3H/HeJ and DBA/2. Furthermore investigations were carried out to examine the effect of the environment on the expression of behavior. After these experiments had proved that there is a predominantly genetic derivation for behavioral expression, a possible relationship between the conditioning effect and the age of the animals was investigated. The animal's age has quantitative effects on the expression of behavior, but it does not lead to any qualitative behavioral changes. Nevertheless early conditioning of the animals apparently manifests itself in long-term memory. On the whole the mode of inheritance in Water-T-Maze learning appears to imply a polygene-dependent model in which clear dominant effects are present, as shown in the results of the F₂-generation. No sex-related differences were observed. In general, the results demonstrate a definite involvement of genetic factors in the areas of conditioning and behavior.     

Genetically-determined abnormal behavior in dogs: Results of behavioral tests

Starting with relatively stable and with very timid purebred pointer stock, we have accumulated data on exploratory activity, reactions to a loud noise, and reactions to friendly and threatening humans which demonstrate clear-cut strain differences. These differences appear as early as 2 months on some tests, and later at early maturity on others. A general factor of fear or timidity explains most of the atypical behavior of the unstable animals. Further, the consistency of results over three generations of offspring suggests a relatively simple mode of autosomal inheritance.     

Time course of changes in novice jumpers' countermovement vertical jump performance

Time course of changes in jump height was examined to assess whether it was related to changes in the underlying mechanics or muscle activity. In Phase I, 11 novice female students performed 10 maximal jumps for eight consecutive days from two force plates. Jump height, impulse duration (t(IMP)), and mean vertical ground reaction force (VGRF) were compared using repeated-measures analysis of variance. Jump height was significantly higher (7.7%) on Days 3-8 when compared to Days 1 and 2; t(IMP) and VGRF were unchanged across days. In a followup study (Phase II), 14 novice female students performed 10 maximal jumps for five consecutive days. Electromyographic activity of five leg muscles was recorded to identify the relative onset of each muscle's activity. Using repeated-measures analysis of variance, jump height was significantly higher (4.2%) on Days 2 to 5 compared to Day 1; however, no significant changes were found across Days, for t(IMP), VGRF, or the onset of muscle activity. The findings indicate that jump performance can improve rapidly in novice jumpers but the underlying muscle activation remained unchanged.     

A Twin and Family Study of the Association Between Immune System Dysfunction and Dyslexia Using Blood Serum Immunoassay and Survey Data

We conducted a study of the association between developmental reading disability (DRD) and immune disorders (ID) using both survey and immunoassay data in two separate samples of families. One sample was made up of twins and their parents and was ascertained through a population-based sampling scheme. The other sample was a set of extended pedigrees selected for apparent autosomal dominant transmission of DRD. We failed to find an association between DRD and ID in either sample, regardless of the method used to assess immune system function. Even though our twin sample provided evidence that both DRD and immune conditions were significantly heritable, there was no evidence for a genetic correlation between ID and DRD nor was there any clear indication that a special subgroup of individuals may be comorbid for these conditions because of genetic reasons. How these negative findings can be reconciled with the developmental hypothesis of Geschwind, Behan, Galaburda, and colleagues, and how they may relate to the gene locus influencing DRD that has been recently located in the HLA region of the short arm of chromosome 6 is discussed.     

Family Communication in Inherited Cardiovascular Conditions in Ireland

Over 100,000 individuals living in Ireland carry a mutated gene for an inherited cardiac condition (ICC), most of which demonstrate an autosomal dominant pattern of inheritance. First-degree relatives of individuals with these mutations are at a 50 % risk of being a carrier: disclosing genetic information to family members can be complex. This study explored how families living in Ireland communicate genetic information about ICCs and looked at the challenges of communicating information, factors that may affect communication and what influence this had on family relationships. Face to face interviews were conducted with nine participants using an approved topic guide and results analysed using thematic analysis. The participants disclosed that responsibility to future generations, gender, proximity and lack of contact all played a role in family communication. The media was cited as a source of information about genetic information and knowledge of genetic information tended to have a positive effect on families. Results from this study indicate that individuals are willing to inform family members, particularly when there are children and grandchildren at risk, and different strategies are utilised. Furthermore, understanding of genetics is partially regulated not only by their families, but by the way society handles information. Therefore, genetic health professionals should take into account the familial influence on individuals and their decision to attend genetic services, and also that of the media.     

Biochemical costs of a three day long cohabitation in dominant and submissive male Betta splendens

A 3 day long cohabitation in pairs of previously isolated adult male Betta splendens was studied. The first two mornings started with intense fighting, the frequency of which decreased during the day. The bursts of aggression noticed in the mornings were associated with a significant carbohydrate metabolism activation, while daytime activity resulted in a reduction of muscle proteins in the evenings. These changes were more pronounced in submissives than in dominants. The third day marked a shift in the behavior of the pairs: bursts of attack activity were not noticed, while the threatening display frequency increased. During this day a similar reduction in lipids was observed in dominants and submissives. While during the first 2 days the dominant position offered some metabolic advantage, this advantage disappeared during the third day when both members of the dyad seemed to do equally less well than their isolated counterparts. Combined with previous findings obtained in this series of experiments, the present results support the assumption that in this species the presence of one opponent is less well tolerated than the presence of four conspecifics. © 1994 Wiley-Liss, Inc.     

双血供胸大肌皮瓣修补咽颈部缺损

探讨双血供胸大肌皮瓣修补咽颈部缺损的可行性。介绍应用双血供胸大肌皮瓣修补咽颈部缺损36例,窄蒂胸大肌皮瓣修补咽颈部缺损7例。结果前者愈合23例,出血3例,感染5例,咽瘘5例,皮瓣坏死无;后者愈合2例,出血1例,感染1例,咽瘘2例,皮瓣坏死1例。双血供胸大肌皮瓣修补咽颈部缺损更利于术后愈合、预防咽瘘。     

Parental Decisions Regarding a Prenatally Detected Fetal Chromosomal Abnormality and the Impact of Genetic Counseling: An Analysis of 38 Cases with Aneuploidy in Southeast Turkey

This study investigated parental decision-making to terminate or continue a pregnancy after prenatal diagnosis of a chromosomal abnormality among a sample of patients in Southeast Turkey. Between 2004 and 2007, 1068 amniocentesis tests were performed in the Medical Biology and Genetic Department Laboratory at Dicle University. Aneuploidy was found in 38 cases (3.56%). Genetic counseling was provided for the couples that received abnormal results, and they were later interviewed and asked if they had continued or interrupted the pregnancy after the diagnosis. When confronted with autosomal aneuploidy in which a severe prognosis was expected, 85% of cases decided to terminate the pregnancy. When confronted with sex chromosome aneuploidy with a low risk of an abnormal clinical phenotype 60% of cases decided to continue the pregnancy. Among the diagnoses with aneuploidy, pregnancy was continued in 21.1% of cases due to religious beliefs regardless of whether there was a low or severe risk of an abnormal clinical phenotype. These findings indicate that both severity of abnormality and religiosity play an important role in genetic counseling patients’ decision-making processes and outcomes in Turkey. In addition, the findings suggest the need for legislation that reduces the differences in approaches between the physicians and institutions regarding parental decision-making to terminate or continue a pregnancy in our country.     

Pavlov's view of the inheritance of acquired characteristics as it relates to theses concerning scientific change

Pavlov's position on the inheritance of acquired characteristics was used to test selected theses of Laudan et al. (1986) concerning scientific change. It was determined that, despite negative experimental findings, Pavlov continued to accept the possibility of the inheritance of acquired habits. This confirms the main thesis I that, once accepted, theories persist despite negative experimental evidence. Pavolv's adherence to the concept of inheritance of acquired characteristics might possibly be explained by his early experiences. Adolescent readings of a popularized version of Darwin's theory, which included the concept of inheritance of acquired characteristics, profoundly influenced Pavlov's subsequent intellectual life. Overwhelmed by the theory, as originally presented, Pavlov was unable to alter his views in light of contrary findings.     

The effects of trunk extensor and abdominal muscle fatigue on postural control and trunk proprioception in young,healthy individuals

The purpose of this study was to induce both trunk extensor and abdominal muscle fatigue, on separate occasions, and compare their effects on standing postural control and trunk proprioception, as well as look at the effects of a recovery period on these outcome measures. A total of 20 individuals participated, with 10 (5 males and 5 females) completing either a standing postural control or lumbar axial repositioning protocol. Participants completed their randomly assigned protocol on two occasions, separated by at least 4 days, with either their trunk extensor or abdominal muscles being fatigued on either day. Postural control centre of pressure variables and trunk proprioception errors were compared pre- and post-fatigue. Results showed that both trunk extensor and abdominal muscle fatigue significantly degraded standing postural control immediately post-fatigue, with recovery occurring within 2 min post-fatigue. In general, these degradative effects on postural control appeared to be greater when the trunk extensor muscles were fatigued compared to the abdominal muscles. No statistically significant changes in trunk proprioception were found after either fatigue protocol. The present findings demonstrate our body’s ability to quickly adapt and reweight somatosensory information to maintain postural control and trunk proprioception, as well as illustrate the importance of considering the abdominal muscles, along with the trunk extensor muscles, when considering the impact of fatigue on trunk movement and postural control.     

Chotzen-Saethre syndrome with oligophrenia and psychological abnormal development

A weak minded man aged 31 years exhibited with moderate acrobrachycephalia, basal cutaneous syndactylies of the 2nd and 3rd fingers, marking symptoms of the Saethre-Chotzen syndrome (SCS), with dominant inheritance in three generations. Additionally there were symptoms of Ascher's syndrome, blepharochalasis, goitre and broad lower lip. The psychic maldevelopment is considered in association with a syndrome of the frontal lobe. Severe craniostenosis is rare at SCS; cosmetic handicap and obstruction of the nasal airway can be corrected by craniofacial surgeon.     

Behavioral comparisons of nervous,stable, and crossbred pointers at ages 2, 3, 6, 9, and 12 months

To clarify some effects of inheritance on abnormal behavior we have maintained by line breeding and selective matingnervous (E) andstable (A) strains within the pointer breed of dogs. We now have comparable measures on behavioral tests of brief activity, startle reactions to a 122-decibel hom, and reactions to humans (Effect of Person) at ages 2, 3, 6, 9, and 12 months, for the two strains as well as for 26 crossbred offspring. In spite of the small crossbred (AE) sample size and limitations of a general nature, the offspring performances are surprisingly like the nervous side of their ancestry, suggesting dominant inheritance.