Pseudocholinesterase activity and E1 phenotypes in Down's syndrome and mental retardation.

Pseudocholinesterase activity and the phenotypes controlled by the E1 locus have been determined in a sample of 307 Down's syndrome patients and 206 patients suffering from nonspecific mental retardation and compared to those in the healthy population. Both groups of patients have an elevated frequency of phenotypes possessing the rate E1f allele. The mentally retarded patients have a higher mean pseudocholinesterase activity than those with Down's syndrome who, in turn, have activity than the healthy controls.     

Relationship between dermatoglyphic variability and finger length in genetic disorders: Down's syndrome]

Palmar and digital dermatoglyphics were compared in Down's syndrome patients with that in a control sample from a population. All dermatoglyphic changes characteristic of Down's syndrome were confirmed. The ridge counts along digital midlines were significantly lower in Down patients as compared to control data, especially, in little fingers, which corresponds to finger shortening in Down's syndrome. The findings agree with a suggestion that digital growth in man could be controlled by morphogenetic gradients which may be altered in genetic disorders.     

Chromatin structure in Down's syndrome.

In the chromatin of patients with Down's syndrome, changes are shown to occur in a short-term lymphocyte culture of the human peripheral blood. Some of them are induced by the patient's blood serum and are reversible when this is replaced by normal serum. A 100-fold dilution of the blood serum taken in subjects with Down's syndrome does not produce any changes in the structure of the lymphocyte chromatin of the patients. A similar procedure with the blood serum of healthy donors resulted in a drastic activation of their lymphocyte chromatin. These experiments, and investigations on the effect produced by the blood serum on the model desoxyribonucleoprotein systems, support the suggestion that the changed state of the chromatin in subjects with Down's syndrome is caused by a complex set of components contained in the blood serum, whose degree of dissociation deviates from the normal.     

Immunological aberrations in patients with aneuploid chromosome abnormalities and in their parents

Summary Studies of autoantibody reactions towards different organs in patients with aneuploid sex chromosome aberrations have been controversial, and no conclusions can be drawn at present. If the findings by certain authors of increased thyroid autoantibody titers in patients with Down's syndrome as well as in the mothers are confirmed by further studies, this might indicate that the increased thyroid autoantibody titers found in mothers of patients with Down's syndrome in some way might be aetiologically connected with the risk of non-disjunction resulting in trisomy 21.     

Lymphocyte proliferation in Down's syndrome measured by sister chromatid differential staining

Summary Lymphocyte proliferation in PHA stimulated cultures from Down's syndrome patients and normals was measured by the BrdU/Giemsa method for demonstrating sister chromatid differential staining. Both Down's syndrome patients and normals had 1st, 2nd and 3rd divisions present. However, Down's syndrome patients had more 3rd division metaphases and fewer 2nd division metaphases than the normals. There was no difference in the mitotic index between the two groups.     

Familial transmission of a (21q22q) translocation.

A large family is described in which a (21q22q) Robertsonian translocation is segregating through three generations. The assessment of the risk of a translocation carrier producing an offspring with Down's syndrome is calculated from the data in this family and eight others reported in the literature. The risk when the translocation carrier is a female is approximately 6 in 100, or 0.06. For the male translocation carrier the risk can only be guessed, since the patients with Down's syndrome born to these parents were probands. The risk for Down's syndrome from the combined data of male and female translocation carriers in 3 is 100, or 0.03.     

Two cases of trisomy 21 and one XXY case with atypical clinical features

Summary Three patients with mental retardation and multiple congenital abnormalities are described.Although their clinical appearance was not suggestive of Down's syndrome, chromosome studies showed a non-disjunctional trisomy 21 in two of the patients. The third case had an unsuspected XXY karyotype.     

Radiosensitivity of chromosomes in lymphocytes from Down's syndrome patients

A study was made of the yield of chromosome aberrations in gamma-irradiated G0 peripheral blood lymphocytes from 6 patients with different forms of Down's syndrome. The doses used were from 0.25 to 3.0 Gy. Seven healthy donors of different age made the control group. There was a significant increase in the yield of chromosome exchanges in lymphocytes from all the patients as compared to control. The spontaneous level of chromosome aberrations and the frequency of radiation-induced fragments did not differ from the control values. The yield of exchanges in diploid and trisomic cells from patients with the mosaic form of Down's syndrome did not change significantly as the time of cultivation was raised. The origin of DNA repair defects leading to the increased chromosome radiosensitivity in Down's syndrome is discussed.     

Red blood cell glucose metabolism in Down's syndrome

The specific activity of red blood cell glycolytic enzymes was determined in 20 Down's syndrome patients and compared with 20 normal controls. According to previous evidence, a 50% increase of phosphofructokinase and a 30% increase of glucose-6-phosphate dehydrogenase and glutathione peroxidase activity was found. Metabolic studies of the patients' erythrocytes revealed a decrease in fructose-6-phosphate and 2, 3-diphosphoglycerate concentrations, while fructose-1, 6-diphosphate and ADP both increased. Glucose utilization by intact erythrocytes from Down's syndrome patients did not differ from that of normal controls. However, addition of methylene blue or inorganic phosphate produced a higher stimulation of erythrocyte glycolysis in patients with Down's syndrome compared to controls. These metabolic abnormalities could be, at least in part, ascribed to the increased phosphofructokinase activity which is due to a gene-dosage effect.     

Trisomy 6p22→6pter due to familial t(6;13)(p22;q34 or 33) translocation

Summary 235 cases of Down's syndrome were ascertained in a 10-year study of Down's syndrome in Western Australia. Although cytogenetic studies performed on 222 subjects confirmed that 95% of cases were trisomic due to nondisjunction, 4% were trisomic due to translocation, and 1% were mosaic, the ratio of inherited/sporadic translocations differed from that usually reported. Comparison of the results with those of an earlier Australian survey of Down's syndrome demonstrated a real fall in the incidence of Down's syndrome in Australia but no significant change in maternal age-specific incidences.     

Non-random centromere division: a mechanism of non-disjunction causing aneuploidy?

Early centromere separation was investigated in 12 normal children, 14 patients with Down's syndrome and in 12 patients of children with autosomal trisomies. A significantly non-random centromere division of chromosomes was found in each of the cases. A higher frequency of early separated G chromosomes was observed in Down's syndrome. In 2 mothers of trisomy-18 patients, the early division of chromosomes 18, generally seen in normal individuals, could not be demonstrated. The possible assoication between altered sequence of centromere disision and non-disjunction needs further confirmation.     

Down's syndrome: abnormal neuromuscular junction in tongue of transgenic mice with elevated levels of human Cu/Zn-superoxide dismutase

To investigate the possible involvement of Cu/Zn-superoxide dismutase (CuZnSOD) gene dosage in the neuropathological symptoms of Down's syndrome, we analyzed the tongue muscle of transgenic mice that express elevated levels of human CuZnSOD. The tongue neuromuscular junctions (NMJ) in the transgenic animals exhibited significant pathological changes, namely, withdrawal and destruction of some terminal axons and the development of multiple small terminals. The ratio of terminal axon area to postsynaptic membrane decreased, and secondary folds were often complex and hyperplastic. The morphological changes in the transgenic NMJ were similar to those previously seen in muscles of aging mice and rats as well as in tongue muscle of patients with Down's syndrome. The findings suggest that CuZnSOD gene dosage is involved in the pathological abnormalities of tongue NMJ observed in Down's syndrome patients.     

Dermatoglyphics of Down's syndrome patients in Malays--a comparative study

There has been no recent report on the dermatoglyphics of the Malays (normal population as well as patients with Down's syndrome). A study on the frequencies of the dermal patterns (dermatoglyphics) of the digits, palms and hallucal areas was done therefore in 40 Malay patients with Down's syndrome and 200 unrelated normal controls. Only the patients with the standard 21 trisomy karyotype were included in the study. Comparison was made with the published data on studies done in various racial groups. Significant differences of the dermal patterns were found not only between the controls but also among patients of different races.     

Ultrastructure of amyloid fibrils in Alzheimer's disease and Down's syndrome

Amyloid fibrils in brains of patients with Alzheimer's disease and Down's syndrome were examined by light and electron microscopy. In addition, replicas of amyloid fibrils produced by a quick freezing method from the brain of a patient with Down's syndrome were examined by electron microscopy. The amyloid fibrils were shown to consist of hollow rods. These were composed of filaments arranged as a tightly coiled helix, each turn of which consisted of five globular subunits. This structure appears to be similar to the prion filament observed in Creutzfeldt-Jakob disease (CJD). The possibility therefore arises that amyloid fibrils in Alzheimer's disease and Down's syndrome may be related to the transmissible agents responsible for diseases such as CJD, kuru and Gerstmann-Str?ussler Syndrome (GSS).     

Birth weight corrected for gestational age is related to the incidence of Down's syndrome pregnancies.

Three recent studies reported that early depletion of the primordial follicle pool is likely to be an independent risk factor for Down's syndrome pregnancies. The size of the primordial follicle pool at birth is determined by oogenesis and by the rate of follicle atresia during the intra uterine period. Since intra uterine growth retardation was reported to be associated with a significantly reduced primordial follicle pool at birth, we investigated the possibility of a relation between low birth weight for gestational age and the risk of a Down's syndrome pregnancy. In a case control study, 95 women with a history of a Down's syndrome pregnancy and 85 controls provided information on their own birth weight and length of gestation. Birth weight standard deviation scores, indicating the difference in birth weight from a reference group, were significantly lower in Down's syndrome mothers than in controls. These findings illustrate that the risk of a Down's syndrome pregnancy is related to a low birth weight corrected for gestational age, possibly by a causal relation between intra uterine growth retardation and the size of the primordial follicle pool.     

Short rib-polydactyly syndrome,Majewski type,in two male siblings

Summary C-band polymorphisms of chromosomes 1, 9, and 16 were investigated in (1) 165 newborn infants, (2) 93 Down's syndrome patients, (3) 69 patients with acquired mental retardation, (4) 54 idiopathic patients, and (5) 48 idiopathics with multiple congenital malformations. The C-band size of chromosomes 1 and 9 showed a similar nonnormal distribution in all five groups. A significantly higher frequency of C bands, some of which were located on the short arm of chromosome 9, was observed in the groups of patients with Down's syndrome and with idiopathic mental retardation.     

Reexamination of paternal age effect in Down's syndrome

Summary The recent discovery that the extra chromosome in about 30% of cases of 47, trisomy 21 is of paternal origin has revived interest in the possibility of paternal age as a risk factor for a Down syndrome birth, independent of maternal age. Parental age distribution for 611 Down's syndrome 47,+21 cases was studied. The mean paternal age was 0.16 year greater than in the entire population of live births after controlling for maternal age. There was no evidence for a significant paternal age effect at the 0.05 level. For 242 of these Down's syndrome cases, control subjects were selected by rigidly matching in a systematic manner. Paternal age was the variable studied, with maternal age and time and place of birth controlled. There was no statistically significant association between paternal age and Down's syndrome. After adjustment for maternal age, these two studies were not consistent with an increase of paternal age in Down's syndrome.     

Dermatoglyphics of schizophrenics, patients with Down's syndrome and mentally retarded males as compared with Australian Europeans using multivariate statistics.

Dermatoglyphics of schizophrenics, patients with Down's syndrome and mentally retarded males were compared with those of normal Australian Europeans. A computer programme of multivariate analysis of fifteen dermatoglyphic features was utilized. This analysis produces two significant variates of each of the populations plotted in two-dimensional space. The distance, measured in arbitrary units, between any two populations was studied for its significance. It was noticed that the patients with Down's syndrome separated significantly from the rest of the groups. The importance of multivariate analysis in the study of dermatoglyphics in comparing two or more populations is discussed.     

多重实时荧光PCR相对定量法快速诊断唐氏综合征

为了建立一种基于多重实时荧光相对定量PCR技术并应用之于唐氏综合征分子诊断, 选择21号染色体上唐氏综合征特异区域基因片段(DSCR3)为目的基因, 以12号染色体上的磷酸甘油醛脱氢酶基因(GAPDH)为参照基因, 设计合成两对引物以及分别以不同荧光标记的TaqMan探针, 在同一个反应管中进行扩增。以相对定量指标△CT值区分唐氏综合征患者与正常人。采用EB 病毒转化技术, 把唐氏综合征患者外周血B 淋巴细胞转化成永生淋巴母细胞系作为标准品。通过优化反应条件, 使得目的基因和参照基因的扩增效率基本一致, 接近100%, 模板浓度在3～300 ng/μL范围内, △CT值的变异系数小于15%, 浓度在30 ng/μL时, 变异系数最小(＜10%), 以该浓度的DNA作为模板进行批内和批间实验的△CT值重复性好, 变异系数分别为9.8%和13.3%。运用建立的方法检测20例唐氏综合征患者的血标本和30例正常人的血标本, 正常人△CT值范围是-1.90～-1.30, 患者的△CT值范围是-2.95～-2.15, 两组之间无交叉重叠, 有明显差异(P＜0.001)。唐氏综合征患者永生细胞系建系成功 ,染色体核型和DNA 分析表明建系前后遗传是稳定的。因此, 实时荧光定量PCR比较△CT值的相对定量法快速诊断唐氏综合征是可行的。     

Identification of G group anomalies in Down's syndrome by quinacrine dihydrochloride fluorescence staining

Summary 9 patients with regular trisomic Down's syndrome, 3 female carriers from different t (DqGq) families and 2 carriers from the same t (21q22q) family were examined by quinacrine dihydrochloride fluorescence microscopy. A G group chromosome with a highly fluorescent band on its long arm was found in triplicate in all patients. The same chromosome was missing in the (DqGq) translocation carriers being involved in the translocation with a D chromosome. It was also missing in the (21q22q) carriers. This supports the suggestion that it is always the same chromosome which is involved in both regular and translocation Down's syndrome.Quinacrine dihydrochloride is an easily available stain, which can be used for identification of human metaphase chromosomes.