To compare cell adhesion molecules levels in cerebrospinal fluid (CSF) between Zika virus (ZIKV)-exposed neonates with/without microcephaly (cases) and controls, 16 neonates (cases), 8 (50%) with and 8 (50%) without microcephaly, who underwent lumbar puncture (LP) during the ZIKV epidemic (2015-2016) were included. All mothers reported ZIKV clinical symptoms during gestation, all neonates presented with congenital infection findings, and other congenital infections were ruled out. Fourteen control neonates underwent LP in the same laboratory (2017-2018). Five cell adhesion proteins were measured in the CSF using mass spectrometry. Neurexin-1 (3.50 [2.00-4.00] vs. 7.5 [5.00-10.25], P = 0.001), neurexin-3 (0.00 [0.00-0.00] vs. 3.00 [1.50-4.00], P = 0.001) and neural cell adhesion molecule 2 (NCAM2) (0.00 [0.00-0.75] vs. 1.00 [1.00-2.00], P = 0.001) were significantly lower in microcephalic and non-microcephalic cases than in controls. When these two sub-groups of prenatally ZIKA-exposed children were compared to controls separately, the same results were found. When cases with and without microcephaly were compared, no difference was found. Neurexin-3 (18.8% vs. 78.6%, P = 0.001) and NCAM2 (25.0% vs. 85.7%, P = 0.001) were less frequently found among the cases. A positive correlation was found between cephalic perimeter and levels of these two proteins. Neurexin-2 and neurexin-2b presented no significant differences. Levels of three cell adhesion proteins were significantly lower in CSF of neonates exposed to ZIKV before birth than in controls, irrespective of presence of congenital microcephaly. Moreover, the smaller the cephalic perimeter, the lower CSF cell adhesion protein levels. These findings suggest that low CSF levels of neurexin-1, neurexin-3 and NCAM2 may reflect the effects of ZIKV on foetal brain development.

暂无摘要。

Antibodies of the IgM isotype are often neglected as potential therapeutics in human trials, animal models of human diseases as well as detecting agents in standard laboratory techniques. In contrast, several human IgMs demonstrated proof of efficacy in cancer models and models of CNS disorders including multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). Reasons for their lack of consideration include difficulties to express, purify and stabilize IgM antibodies, challenge to identify (non-protein) antigens, low affinity binding and fundamental knowledge gaps in carbohydrate and lipid research. This manuscript uses HIgM12 as an example to provide a detailed protocol to detect antigens by Western blotting, immunoprecipitations and immunocytochemistry. HIgM12 targets polysialic acid (PSA) attached to the neural cell adhesion molecule (NCAM). Early postnatal mouse brain tissue from wild type (WT) and NCAM knockout (KO) mice lacking the three major central nervous system (CNS) splice variants NCAM180, 140 and 120 was used to evaluate the importance of NCAM for binding to HIgM12. Further enzymatic digestion of CNS tissue and cultured CNS cells using endoneuraminidases led us to identify PSA as the specific binding epitope for HIgM12.

OBJECTIVE: To offer data on the phenotype determined by microdeletions of alpha exons in the NRXN1 gene.
METHODS: Three neuropaediatric cases of intragenic microdeletions of NRXN1 alpha are studied. The phenotype of these three cases is unspecific, with mild-moderate mental retardation, behavioural disorders and slight dysmorphic traits or malformations.
CONCLUSIONS: The phenotype found in the microdeletions of alpha exons of the NRXN1 gene is clearly distinguishable from the one found in the microdeletions of beta exons, with macrocephaly, epilepsy and mental retardation.
Deleciones intragenicas NRXN1: aportacion de tres nuevos casos y revision del fenotipo.
Objetivo. Aportar datos sobre el fenotipo determinado por las microdeleciones de los exones alfa del gen NRXN1. Casos clinicos. Se estudian tres casos neuropediatricos con microdeleciones intragenicas NRXN1 alfa. El fenotipo en estos tres casos es inespecifico, con retraso mental leve-moderado, trastornos de comportamiento y escasos rasgos dismorficos o malformaciones. Conclusion. El fenotipo encontrado en las microdeleciones de los exones alfa del gen NRXN1 es claramente distinguible del fenotipo encontrado en las microdeleciones de los exones beta, con macrocefalia, epilepsia y retraso mental.

Ovarian pulmonary-type small cell carcinoma is a rare and extremely aggressive neoplasm. We report the occurrence of an ovarian small cell carcinoma of pulmonary type in a 54-year-old woman. She underwent a total abdominal hysterectomy with a bilateral salpingo-oophorectomy and infracolic omentectomy. A diagnosis of stage IIIA pulmonary-type small cell carcinoma was rendered. The tumor appeared to be composed of a solid growth of small cells arranged in sheets and closely packed nests with insular arrangements separated by a fibrous stroma. The tumor cells had hyperchromatic nuclei with inconspicuous nucleoli and scanty cytoplasm. Rosette and rosette-like structures were scattered. Immunohistochemical staining showed positivity for synaptophysin, neural cell adhesion molecule (NCAM), and focally for chromogranin. Cytokeratin and neuron-specific enolase (NSE) were also positive. Over 80% of the tumor cells showed strong reactivity for MIB-1. Electron microscopy showed neuroendocrine granules. She was effectively treated with paclitaxel plus carboplatin after the surgery.

BACKGROUND: Recent research has implicated that mutations in the neurexin-1 (NRXN1) gene on chromosome 2p16.3 might play a role in schizophrenia, autism, and nicotine dependence. In order to explore the association of NRXN1 polymorphisms with schizophrenia, we made a case-control association study in Chinese Han population.
METHODS: We examined six tag single nucleotide polymorphisms (SNPs) spanning 116.7 kb of NRXN1 in 768 schizophrenic patients and 738 healthy control subjects. The association of NRXN1 polymorphisms with schizophrenia and the age-at-onset of this disease were explored.
RESULTS: Our results showed that four SNPs of NRXN1 gene were significantly associated with schizophrenia (rs10490168: G > A, p = 0.017; rs2024513: A > G, p = 0.006; rs13382584: T > C, p = 0.009; and rs1558852: G > A, p = 0.031). Furthermore, the association of SNP rs2024513 with schizophrenia remained significance after the Bonferroni correction. Haplotypes consisting of above six SNPs also showed significantly associated with schizophrenia (global chi-square = 14.725, p = 0.022). A protective haplotype AGTGCA remained associated with schizophrenia, even after 10,000 permutation tests (empirical p-value = 0.043). However, we did not find any association with age-at-onset of schizophrenia with NRXN1 polymorphisms.
CONCLUSIONS: Our findings suggest that NRXN1 might represent a major susceptibility gene for schizophrenia in Chinese Han population.

There have been many conflicting reports concerning the association of the DRD2 locus with alcohol dependence (AD). To investigate whether these findings could be reconciled by considering the genomic region of DRD2 in greater detail, we conducted two separate association studies of AD in 1220 European-American subjects using family-based (488 subjects) and case-control (318 cases and 414 controls) designs, and 43 single nucleotide polymorphisms mapped to the gene cluster of NCAM1, TTC12, ANKK1 and DRD2. We used a generalized linear model and haplotype score tests for the case-control sample, and the family-based association test for the family sample. Haplotype associations centered on TTC12 exon 3 [rs1893699-rs723077; optimal individual haplotype simulated P-value (P(oihs)) = 0.00021] in both independent samples (family and case-control). Additional AD-associated haplotypes centered around NCAM1 exon 12 in the family sample (P(oihs) = 0.0032), and at exons 2 and 5 of ANKK1 in the case-control sample (P(oihs) = 0.00058). LD contrasts between cases and controls support selection at TTC12 exon 3 and ANKK1 exon 2. The armadillo repeat domains encoded by TTC12 and dopamine interact in the Wnt pathway and may have effects on dopamine cell development in the ventral midbrain. We conclude that risk for AD is attributable in part to variants in four regions within this cluster: exon 3 of TTC12, exon 12/intron13 of NCAM1 and exons 2 and 5 of ANKK1. The complexity of these relationships, many of which replicate between our independent samples, may explain prior inconsistent results.

BACKGROUND: X-linked hydrocephalus (HLX) is a form of hydrocephalus with recessive transmission linked to the X chromosome, and a recurrence rate of 50% in male foetuses. It is the commonest genetic form of congenital hydrocephalus, with an incidence of 1/30,000 male births. It is characterized by dilation of the lateral ventricles and mental retardation, usually severe. Other common characteristics are abducted thumbs and spastic paraplegia (or quadriplegia).
METHODS: A baby whose family and clinical history, neuroimaging and genetic studies lead to the diagnosis of HLX.
CONCLUSIONS: Identification of the mutation L1CAM in this family will permit identification of the carriers and make it possible to give genetic counselling and prenatal diagnosis.

Desmoplastic small round-cell tumor typically occurs in the abdomen of young men, but it can also develop at other anatomic sites and in older people, presenting greater diagnostic difficulties. We report a case of this tumor arising from the paratesticular region in a 43-year-old man. The tumor showed histologic, immunohistochemical, and ultrastructural evidence of multilineage differentiation, including epithelial, mesenchymal, and neuronal features. In addition, the presence of an EWS and WT1 chimeric messenger RNA was demonstrated by the reverse transcriptase-polymerase chain reaction using an EWS exon 7 primer and WT1 exon 8 and exon 9 primers, which revealed single polymerase chain reaction products with a junction of EWS exon 7 to WT1 exon 8. Our study demonstrates that desmoplastic small round-cell tumors of the paratesticular region share not only morphologic but also molecular genetic features with those of the abdomen and that reverse transcriptase-polymerase chain reaction analysis using paraffin sections is useful for a conclusive diagnosis.

OBJECTIVE: The mechanisms by which the sex ratio might be altered at fertilization were reviewed, following a case of preimplantation gender analysis revealing a significantly skewed proportion of male-to-female embryos.
METHODS: The case of a known carrier of X-linked hydrocephalus with a history of three affected male pregnancies is presented. Her husband\'s family history consisted of a strong increase in the number of males relative to females. She had four cycles of stimulated in vitro fertilization, with sex chromosome analysis using fluorescent in situ hybridization (FISH) on suitable cleavage-stage embryos. The difference in the sex ratio of normal male-to-female embryos was compared using a significance probabilities test for sex ratio. The sex ratio of sperm from a semen sample from the male partner was determined by FISH.
RESULTS: Fifty embryos were suitable for analysis. A significantly higher number of normal male (n = 20) than normal female (n = 8) embryos was obtained (P < 0.05). The FISH assessment of the husband\'s semen analysis revealed no alteration in the normal X:Y ratio.
CONCLUSIONS: As the sperm analysis revealed a normal X:Y ratio, an alteration in the embryo sex ratio might be explained by the preferential binding of Y-bearing sperm to the oocyte, an oocyte-related \"discouragement\" of binding of X-bearing sperm, or a postfertilization event.