Cervico-vaginal immunoglobulin g levels increase post-ovulation independently of neutrophils

The prevalence of sexually transmitted infections (STIs) is often higher in females than in males. Although the reproductive cycle profoundly modulates local immunity in the female reproductive tract (FRT) system, significant gaps in our knowledge of the immunobiology of the FRT still exist. An intriguing and frequently observed characteristic of the FRT is the predominant presence of immunoglobulin (Ig) G in cervico-vaginal secretions. We show here that in the mouse, IgG accumulation was enhanced approximately 5-fold post-ovulation, and was accompanied by an influx of neutrophils into the FRT. To determine whether these two events were causally related, we performed short-term neutrophil depletion experiments at individual stages throughout the estrous cycle. Our results demonstrate that neutrophils were not necessary for cycle-dependent tissue remodeling and cycle progression and that cycle-dependent IgG accumulation occurred independent of neutrophils. We thus conclude that neutrophil influx and IgG accumulation are independent events that occur in the FRT during the reproductive cycle

Diagnosis and management of Cornelia de Lange syndrome:first international consensus statement

Cornelia de Lange syndrome (CdLS) is an archetypical genetic syndrome that is characterized by intellectual disability, well-defined facial features, upper limb anomalies and atypical growth, among numerous other signs and symptoms. It is caused by variants in any one of seven genes, all of which have a structural or regulatory function in the cohesin complex. Although recent advances in next-generation sequencing have improved molecular diagnostics, marked heterogeneity exists in clinical and molecular diagnostic approaches and care practices worldwide. Here, we outline a series of recommendations that document the consensus of a group of international experts on clinical diagnostic criteria, both for classic CdLS and non-classic CdLS phenotypes, molecular investigations, long-term management and care planning

Utility of Measuring Fetal Cavum Septum Pellucidum (CSP) Width During Routine Obstetrical Ultrasound for Improving Diagnosis of 22q11.2 Deletion Syndrome: A Case-Control Study

Christy L Pylypjuk,1 Shiza F Memon,2 Bernard N Chodirker3 1Department of Obstetrics, Gynecology and Reproductive Sciences (Section of Maternal-Fetal Medicine), Children’s Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, MB, Canada; 2Department of Obstetrics, Gynecology & Reproductive Sciences, University of Manitoba, Winnipeg, MB, Canada; 3Departments of Pediatrics and Child Health (Section of Genetics and Metabolism) & Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, MB, CanadaCorrespondence: Christy L Pylypjuk, WN5002, HSC Women’s Hospital, 820 Sherbrook Street, Winnipeg, MB, R3A 1R9, Canada, Tel +1 204 787-4821, Fax +1 204 787-2920, Email [email protected]: To evaluate the utility of measuring fetal cavum septum pellucidum (CSP) width during routine, mid-pregnancy ultrasound for improving diagnosis of 22q11.2 deletion syndrome amongst fetuses with and without conotruncal anomalies.Patients and Methods: This was a retrospective case-control study (2005– 2016). Fetuses and newborns with 22q11.2 deletion and/or conotruncal cardiac anomalies were identified using a regional, clinical database. A control group was assembled in a 2:1 ratio to create three groups for comparison: i) 22q11.2 deletion syndrome; ii) isolated conotruncal anomalies; and iii) controls. Eligibility was restricted to those with stored ultrasound images between 18– 22 weeks’ gestation and a minimum biparietal diameter of 40 mm. Post-processing measurement of CSP width was performed in a standardized fashion by two blinded and independent study personnel. Descriptive and inferential statistics, regression modeling, and receiver operator curves (ROC) were used to compare outcomes between groups and evaluate sensitivity/specificity of CSP width as a marker of 22q11.2 deletion syndrome.Results: Twenty-nine cases of 22q11.2 deletion and 64 cases of isolated conotruncal anomalies were matched to 186 healthy controls. Cases with 22q11.2 deletion syndrome had significantly larger CSP widths (5.36 mm; SD=1.2) compared to those with isolated conotruncal anomalies (3.75 mm; SD=1.11) and healthy controls (2.93 mm; SD=0.57; p 4.3 mm, fetuses with 22q11.2 deletion can be accurately identified with good sensitivity (89.7%) and specificity (84%).Conclusion: Fetuses with 22q11.2 deletion syndrome have dilated CSPs when compared to those with isolated conotruncal anomalies or controls. Because CSP dilation can be evaluated during routine mid-pregnancy ultrasound using standard images of the fetal head, measurement could easily be incorporated to enhance prenatal diagnosis of this phenotypically diverse condition.Keywords: DiGeorge syndrome, 22q11 microdeletion, cavum septum pellucidum, prenatal diagnosis, fetal ultrasound, neurosonograph

Disrupted auto-regulation of the spliceosomal gene SNRPB causes cerebro-costo-mandibular syndrome

Elucidating the function of highly conserved regulatory sequences is a significant challenge in genomics today. Certain intragenic highly conserved elements have been associated with regulating levels of core components of the spliceosome and alternative splicing of downstream genes. Here we identify mutations in one such element, a regulatory alternative exon of SNRPB as the cause of cerebro-costo-mandibular syndrome. This exon contains a premature termination codon that triggers nonsense-mediated mRNA decay when included in the transcript. These mutations cause increased inclusion of the alternative exon and decreased overall expression of SNRPB. We provide evidence for the functional importance of this conserved intragenic element in the regulation of alternative splicing and development, and suggest that the evolution of such a regulatory mechanism has contributed to the complexity of mammalian development

Chromosome abnormalities, mental retardation and the search for genes in bipolar disorder and schizophrenia

Genetic factors contribute to schizophrenia and bipolar disorder, and linkage and association studies have been successful in identifying several candidate genes. However these genes explain only a very small part of the total population risk and the psychoses appear to be very heterogeneous with several models of genetic inheritance relevant to different groups of patients, including some cases caused by multiple common genetic variants, while others are single gene disorders. Studying chromosomal abnormalities is a useful strategy for identifying genes in illness, and patients with both mental retardation and psychosis form a special group where large chromosomal abnormalities detected by routine cytogenetic analysis are more prevalent than in patients with schizophrenia or bipolar disorder alone, or in the general population. Studying these patients provides valuable opportunities to identify genes contributing to psychoses. This review of the literature on large chromosomal rearrangements in patients with mental retardation and psychotic illness illustrates how schizophrenia and bipolar phenotypes are associated with a large number of different chromosomal disruptions. Recent genome wide association studies have identified an excess of small chromosomal deletions and duplications in schizophrenia, adding further support to the importance of chromosomal structural variation in psychotic illness. The genes GRIK4 and NPAS3, each associated with psychosis in patients with mental retardation are discussed to illustrate the value of rare cytogenetic events as a means to signpost neurobiological pathways of general importance for illness in the wider population