Female‐restricted syndromic intellectual disability in a patient from Thailand

Female‐restricted syndromic intellectual disability (ID) is a neurodevelopmental disorder with developmental delay (DD)/ID, facial dysmorphism, and diverse congenital anomalies comprising heart defects, anal anomalies, choanal atresia, postaxial polydactyly, scoliosis, and brain abnormalities. Loss‐of‐function mutations in the USP9X gene inherited as X‐linked dominance were identified as its etiology in females of different ethnic groups. Here, we report a 15‐year‐old Thai girl harboring a novel de novo heterozygous one‐base pair deletion (c.3508delG, p.Val1170TrpfsX9) in exon 23 of USP9X. Her profound DD, dysmorphic face including attached earlobes, short stature, and congenital malformations including s‐shaped thoracolumbar scoliosis, hip dislocation, and generalized brain atrophy shared common characteristics of X‐linked syndromic ID. We have observed severely malformed oro‐dental organs and a choledochal cyst, which have never been reported. Our study presents the first patient from Thailand expanding the phenotypic and mutational spectra of the syndrome.     

Neurophysiological and psychological predictors of genetic risk for schizophrenia

Mathematical genetic analyses were performed on a sample of schizophrenic families (25 probands and 58 first-degree relatives). Heritability coefficients were estimated for EEG power spectrum parameters and their topography, and also for psychological test data on thought and speech process disorder, designed to assess altered selectivity in cognitive activity. Multiple regression equations for genetic counseling regarding the prognosis of mental illness were derived from the neurophysiological and psychological measures.     

New multiple congenital anomalies: Mental retardation syndrome (MCA/MR) with facio-cutaneous-skeletal involvement

Five unrelated patients (a male and 4 females) were affected with a previously undefined multiple congenital anomalies/mental retardation syndrome which has been designated the facio-cutaneous-skeletal (FCS) syndrome and which includes mental retardation with specific sociable, humorous behavior, characteristic facial appearance, excessive generalized skin, postnatal growth failure, and skeletal involvement. Consanguinity was noted in 2 patients, thus autosomal recessive inheritance is suggested. © 1992 Wiley-Liss, Inc.     

Survival rates during the first trimester of multiple gestations achieved by ICSI: a report of 1448 consecutive multiples

BACKGROUND: The purpose of this study was to determine the rate of spontaneous gestational sac loss during the first trimester in women achieving multiple pregnancies by ICSI. METHODS: A retrospective analysis was performed of 1448 consecutive multiple pregnancies conceived by ICSI. RESULTS: Of the cohort of 1448 pregnancies, twin gestations constituted 59.6% (864), triplets 30.2% (438) and quadruplets 10.0% (146). During the first trimester, 69 (4.7%) patients miscarried, while 179 (12.3%) continued their pregnancies and had fewer gestational sacs at the end of the first trimester than at the beginning. The overall loss rate of any gestational sac during the first trimester in these multiple pregnancies was 10.1%. There was a significant difference in the frequency of spontaneous reduction to twin or singleton pregnancies in the first trimester between women carrying triplets (11.7%) and those carrying quadruplets (3.5%) [P = 0.004; odds ratio (OR) 3.5; 95% confidence interval (CI) 1.3-9.1]. The frequency of gestational sac loss was significantly greater among women >35 years old (20.9%) than in women less than 35 years old (15.9%) (P = 0.03; OR 1.4; 95% CI 1.0-1.9). CONCLUSION: In multiple pregnancies there is a significant risk of spontaneous loss of any embryo during the first trimester. These findings should be considered prior to any decision about selective embryo reduction.     

幕上高血压脑出血预后影响因素的多重线性回归分析

目的探讨影响幕上高血压脑出血（SICH）患者预后的相关因素,以指导临床治疗和评估预后。方法回顾性分析符合本研究纳入标准的幕上高血压脑出血324例完整病历。以一般资料、起病症状、入院查体、影像学资料、治疗方式、并发症等43项为自变量,以发病后1个月后功能独立性评定评分（functional independence measure,FIM）为因变量,建立多重线性回归模型,筛选出对预后有影响的因素,并比较各因素的影响大小。结果经统计学处理发现血肿体积、入院时收缩期血压、GCS评分、脑室是否积血、血肿体积扩大、是否并发肺部感染和应激性溃疡等7项对预后有显著性的影响。结论血肿体积、入院GCS评分和脑室是否积血对预后影响有重要意义,可作为SICH患者预后的关键性指标。     

Increased spontaneous immunoglobulin secretion associated with cyclophosphamide-induced immune suppression

Spontaneous immunoglobulin (Ig) secretion by cells from multiple sclerosis (MS) patients (in the progressive phase) treated with monthly pulse doses of cyclophosphamide (CY) (1000–1600 mg/M²) was measured using the protein A plaque assay, to evaluate the effect of CY treatment on B-cell function. Surprisingly, an increase, rather than a decrease, in Ig-secreting cells was seen following CY treatment. CY-treated MS patients averaged 1380±535 spontaneous total (IgM+G+A) Ig plaque-forming cells (PFC) per 1×10⁶ peripheral blood mononuclear cells (MNC), measured at 15–22 days after monthly CY administration, while healthy adults had 280±47 Ig PFC/10⁶ MNC, and MS patients not treated with CY had 300±43 Ig PFC/10⁶ MNC. The observed increase was due to an increase in IgG and IgA PFC. PFC levels remained elevated for 4 weeks following CY treatment, decreasing to control levels by 7–8 weeks post-CY. A small increase in serum IgG level was noted after >12 months of pulse CY therapy; no increase was seen in CSF IgG levels. A preferential decrease in the number of CD4+ T cells was also seen in the CY-treated MS patients. We propose that the observed increase in the number of spontaneous Ig PFC was due to the CY-induced disruption of the CD4+ T cell-mediated control ofin vivo activated B cells.     

Cytokine flow cytometry differentiates the clinical status of multiple sclerosis (MS) patients

In this study we have examined intracellular cytokines in peripheral blood mononuclear cells (PBMC) of MS patients by flow cytometry (cytokine flow cytometry). MS progressive patients showed an increased number of cells producing interferon-gamma (IFN-gamma) after activation with phorbol 12-myristate 13-acetate and ionomycin, compared with patients with clinically inactive forms (P < 0001) and with healthy controls (P = 0001). These cells belonged to the CD4+ and CD8+ subsets in similar proportions. Clinically inactive patients showed a lower level of cells producing IL-2 than controls (P = 0.03) and active MS patients (P = 0.03). Most IL-2-producing cells were CD4+ lymphocytes, although a small part of the IL-2 was also produced by CD8+ cells. The percentage of cells producing simultaneously IL-2 and IFN-gamma was increased in active MS and they were mainly CD4+ lymphocytes. No differences in the production of IL-4 were observed between groups. However, we found an increased IL-10 production in clinically active MS patients (P = 0.03). Treatment with IFN-beta of active MS patients showed lower levels of cytokines when compared with untreated MS patients. This methodological approach could help in the follow up and therapeutic monitoring of MS patients.     

Impact of elective single embryo transfer on the twin pregnancy rate

BACKGROUND: It is unclear how the implementation of elective single embryo transfer in clinical practice would affect clinical pregnancy and delivery rates and multiple birth rates. METHODS: This retrospective study analysed 1871 IVF/ICSI cycles carried out from 1997 to 2001 in the IVF programme of a single university infertility clinic. RESULTS: The number of elective single embryo transfers increased from 11 to 56%. At the same time the clinical pregnancy rate was relatively stable; mean 34.0% (range 28-42). The number of embryos per embryo transfer decreased from 1.8 to 1.3. The multiple pregnancy and delivery rates dropped markedly from 25 to 7.5% and from 25 to 5% respectively. CONCLUSIONS: An elective single embryo transfer programme can be adopted in daily practice that decreases the twinning rate to <10% and does not affect the overall pregnancy rate.     

Heritabilities,by the multiple abstract variance analysis (MAVA) model and objective test measures,of personality traits U.I.23, capacity to mobilize,U.I.24, anxiety,U.I.26, narcistic ego and U.I.28, asthenia,by maximum-likelihood methods

Heritability coefficients are offered for four personality source traits, measured by the O-A (objective-analytic) 2-h performance battery. Five family constellations covering a total sample of 1221 boys 12–18 years old yielded nine concrete variances which the MAVA (multiple abstract variance analysis) model resolves into seven abstract variances: ² _wg , within family genetic; ² _wt.s , within family threptic; ² _wt.t , within family threptic for twins; ² _bg , between family genetic; _bgbt , correlation of genetic and threptic deviations across families, etc. Maximum likelihood was the method here used for the MAVA analysis. The best fit with maximum parsimony was to assume no genothreptic ( _wgwt , _bgbt ) correlations, but extension to the parsimony of assuming either no genetic or no threptic components gave no fit. The heritabilities found were compared with those from an earlier research and from a different (OSES) method applied to the present data. The agreement is quite good in assigning a moderate heritability value tocapacity to mobilize vs. regression, U.I.23 (H about 0.30), and toanxiety, U.I.24 (H about 0.50); only moderately consistent in assigning a moderateH value toasthenia, U.I.28 (H about 0.30); and poorly consistent in assigning a lowH value tonarcistic ego, U.I.26. It is pointed out (a) that the lowH for U.I.28 fits the theory of the origin of this trait well and (b) that, in view of estimates of the function fluctuation of U.I.23 and 24, a most probable conclusion is that a capacity to mobilize is quitesubstantially innate and a general proneness to anxiety islargely innate.     

Combined analysis of T cell receptor gamma and immunoglobulin heavy chain gene rearrangements at the single-cell level in lymphomas with dual genotype

By prospectively studying immunoglobulin heavy chain gene (IgH) and T cell receptor gamma (TCRgamma) gene rearrangements in 398 lymphoma cases, a dual genotype was observed in 13% of B cell and 11% of T cell lymphomas. According to histological subtype, the highest incidence was observed for mantle cell lymphomas (32%) and lymphoplasmacytic lymphoma (21%) among B cell lymphomas, and for angioimmunoblastic lymphoma (AILT) (46%) and Sézary syndrome (SS) (50%) among T cell lymphomas. To determine whether the dual genotype corresponds to the presence of two distinct monoclonal populations or to the presence of both rearrangements within the same lymphoma cells, single-cell microdissection was used after immunohistochemistry and a single-cell combined IgH and TCRgamma gene analysis was designed after a whole-genome amplification step. This protocol was applied to the study of two nodal B cell lymphomas (one diffuse large B cell lymphoma and one mantle cell lymphoma) and two cutaneous T cell lymphomas (one AILT and one SS). Two cases (SS and mantle cell lymphoma) were true bigenotypic lymphomas, as both IgH and TCRgamma monoclonal rearrangements were detected in the same cells. Conversely, in the diffuse large B cell lymphoma and AILT cases, large CD22+ single cells exhibited only the monoclonal IgH rearrangement but not the TCRgamma gene that was detected in CD3+ single cells. Such an approach allows the identification of true bigenotypic lymphoma among dual genotypic lymphoma. Specific genetic alterations may be further amplified from microdissected cryopreserved material, such as the t(11;14) breakpoint detected in bigenotypic B cells of the mantle cell lymphoma case.