Bi-allelic loss of function variant in the NRCAM gene is associated with motor-predominant axonal polyneuropathy; the second report.

BACKGROUND: The role of biallelic variants in the NRCAM gene underlying a neurodevelopmental disorder has been defined recently. The phenotype is mainly recognized by varying severity of global developmental delay/intellectual disability, hypotonia, spasticity, and peripheral neuropathy. METHODS: Here, we describe a patient with an initial diagnosis of motor-predominant axonal polyneuropathy or a form of distal SMA. Whole-exome sequencing (WES), in parallel with WES-based CNV detection and assessment of homozygosity runs, was performed to identify this patient's possible genetic cause. RESULTS: Whole exome sequencing revealed a homozygous variant, c.73C > T (p.Gln25*), in the NRCAM gene, while the patient manifests a mild range of phenotypes compared to NRCAM-related disorder. He presented only motor-predominant axonal polyneuropathy with no other signs of central nervous system involvement. CONCLUSIONS: This study is the second report of an association between biallelic NRCAM gene variants and a Mendelian disorder. The obtained clinical data, together with the molecular findings in this patient, expands the clinical and molecular spectrum of NRCAM-related disorder and highlights its phenotypic complexity. Although patients with loss of function variants in this gene have previously presented severe clinical features, we show that type of the pathogenic variant does not necessarily determine the severity of this phenotype.

Risk factors and clinical significance of abdomino-pelvic free fluid after cesarean section: a prospective study.

Introduction: Post-partum hemorrhage is a major cause of maternal mortality. Ultrasonography is a safe, rapid, and noninvasive diagnostic tool which can be used to identify and measure the abdomino-pelvic free fluid in post-partum period.Objective: This study was conducted to evaluate the risk factors and clinical significance of abdomino-pelvic free fluid after cesarean section.Method: Demographic data, indication of cesarean section, duration of operation, volume of intraoperative blood loss, and instability in vital signs, blood transfusion, decreased Hb level, and decreased urine output were documented in 100 women with cesarean delivery 4 and 24 h after surgery. Abdomino-pelvic free fluid volume was estimated by ultrasound study.Result: Four hours after cesarean, minimal, moderate, and large amount of free fluid was seen in 38(38%), 45(45%), and 17(17%) patients respectively. The volume of free fluid was decreased generally as 73 (73%) of patients had minimal amount of free fluid 24 h after surgery. There was statistically significant relationship between volume of blood loss during cesarean and the volume of free fluid 4 h (and not 24 h) after surgery. There was no statistically significant relationship between duration of operation and the volume of free fluid 4 and 24 h after cesarean. There is statistically significant relationship between free fluid volume 4 h after surgery and hemodynamic instability.Conclusion: Ultrasonography detects even minimal amount of free fluid in post-cesarean patients but cannot predict their clinical course.

Prediction of Stress Urinary Incontinence Using the Retrovesical (ß) Angle in Transperineal Ultrasound.

OBJECTIVES: The accurate, rapid diagnosis of stress urinary incontinence (SUI) in women can profoundly improve their sexual and psychosocial life. In this study, the diagnostic power of SUI was assessed by transperineal ultrasound. METHODS: In this hospital-based case-control study, married women who were referred to the gynecologic and ultrasound wards with negative urinalysis and culture results were enrolled by random sampling. Patients with positive cough signs based on the urodynamic testing data were considered cases, whereas control women showed no cough symptoms and were recruited from the same ward. RESULTS: There was a significant difference (P < .001) in bladder neck descent (mean ± SD, 10.89 ± 5.51 versus 7.08 ± 2.60 mm, respectively; P = .0001) and the retrovesical (ß) angle with the Valsalva maneuver (144.22° ± 19.63° versus 111.81° ± 24.47°; P < .001) between the case and control groups. Also, the ß angle without the Valsalva maneuver was higher in the case group (112.35° ± 23.10°) than the control group (120.17° ± 25.16°; P = .001). There was no case of a urinary leak, urethral diverticulitis, a bladder stone or mass, and cystourethrocele in the patients of each group. The results of multivariate logistic regression with a backward method showed that bladder neck descent (odds ratio [OR], 1.24; 95% confidence interval [CI], 1.09-1.40), the ß angles with and without the Valsalva maneuver (OR, 1.1; 95% CI, 1.06-1.13; and OR, 1.04; 95% CI, 1.01-1.06) were the predictors of SUI. A ß angle higher than 127° with the Valsalva maneuver, with an area under the curve of 0.89 (95% CI, 0.75-0.96), could very well predict the SUI response. This finding shows that it can be very well used to distinguish between normal and non-normal responses, with 89% sensitivity and 79% specificity. CONCLUSIONS: The ß angle with the Valsalva maneuver could very well predict the SUI response.

Effects of Obesity on Axillary Lymph Node Structure: Association of Hilar Fat Deposition and Alterations in Cortex Width.

Introduction: This study aims to evaluate the effects of obesity on the structure of axillary lymph nodes in women with no evidence of breast or axilla pathology. Method: In this prospective study, we documented the body mass index of 204 women who were referred for screening mammography. Two radiologists have independently viewed the mammograms to find the largest axillary lymph node and reported its dimensions. Independent sample T-test was used to evaluate the association of the above indices with participants' body mass index. Associations between indices were investigated using multiple regression analyses. Results: All measurements of axillary lymph nodes and hilo-cortical ratio were significantly increased with increasing body mass index (p<0.001), except for cortex width (p=0.15). There were strong associations (p < 0.001) between increasing hilum length and increasing lymph node length (R²=0.90), increasing hilum width and increasing lymph node width (R²=0.85), and increasing hilum width and decreasing cortex width (R²=0.12). There was no association between cortex width and lymph node width (R²=0.0001). Inter-rater reliability ranged from 0.49 to 0.70. Conclusion: Our study demonstrated that axillary lymph nodes with a bigger hilum width had a smaller cortex width in obese but apparently normal population. Considering the important role of axillary lymph node cortex in their immune function, this may be a cause for immune dysfunction of axillary lymph nodes in obesity and explain the worse prognosis of breast cancer in obese women. The limited number of participants, the 2-dimensional nature of mammograms and the difficulty of measuring the dimensions of axillary lymph nodes using mammography were important limitations of this study. Implications for practice: Obesity may result in structural change and dysfunction of axillary lymph nodes. Dysfunction of axillary lymph nodes may have a role in worse prognosis of breast cancer in obese patients.

A GLI3 variant leading to polydactyly in heterozygotes and Pallister-Hall-like syndrome in a homozygote.

Variants in transcriptional activator Gli Kruppel Family Member 3 (GLI3) have been reported to be associated with several phenotypes including Greig cephalopolysyndactyly syndrome (MIM #175700), Pallister-Hall syndrome (PHS) (MIM #146510), postaxial polydactyly types A1 (PAPA1) and B (PAPB) (MIM #174200), and preaxial polydactyly type 4 (MIM #174700). All these disorders follow an autosomal dominant pattern of inheritance. Hypothalamic hamartomas (MIM 241800) is associated with somatic variants in GLI3. We report a related couple with parents having PAPA1 and PAPB, who had a fetus with a phenotype most compatible with PHS. Molecular analyses demonstrated homozygosity for a pathogenic GLI3 variant (c.1927C > T; p. Arg643*) in the fetus and heterozygosity in the parents. The genetic analysis in this family demonstrates that heterozygosity and homozygosity for the same GLI3 variant can cause a different phenotype. Furthermore, the occurrence of Pallister-Hall-like syndrome in a homozygous patient should be taken into account in genetic counseling of families with PAPA1/PAPB.

Diagnostic triad of pulmonary anthracofibrosis in spiral CT scan - a retrospective study.

PURPOSE: Anthracosis, a form of pneumoconiosis commonly caused by air pollution and other environmental factors, is a new entity in respiratory disorders. Bronchoscopy and transbronchial lung biopsy (TBLB) are the gold standard of diagnosis. Herein, we evaluated the results of bronchoscopy and chest computed tomography (CT) scans of 187 anthracotic patients. MATERIAL AND METHODS: Between April 2016 and April 2017, 187 cases (99 males, mean age 65 ± 10.2 years) who underwent flexible bronchoscopy and TBLB for various indications were considered for this study. CT examinations of these patients were reported as "blind to bronchoscopy results" by two experienced board-certified radiologists. RESULTS: According to the results of bronchoscopy and TBLB, 100 patients were diagnosed as anthracotic. CT scans confirmed 71 of these cases as anthracosis. Sensitivity, specificity, PPV, NPV, and accuracy of hyperdense non-calcified mediastinal and hilar lymph nodes, known as "brilliant lymph nodes", compared to bronchoscopy were 55%, 92%, 89%, 64%, and 72%, respectively (CI: 95%). Also, there was a positive correlation between anthracosis and brilliant lymph nodes (p-value = 0). Analysis of hyper-attenuated lung with bronchoscopy estimated sensitivity, specificity, PPV, NPV, and accuracy gave 41%, 94%, 89%, 58%, and 65%, respectively (CI: 95%). The specificity of brilliant lymph nodes, hyper-attenuated lung, and multi-segmental atelectasis as a diagnostic "triad of anthracosis" was 100%. CONCLUSIONS: Based on our analyses, the triad of brilliant lymph nodes, hyper-attenuated lung, and multi-segmental atelectasis was identified as a reliable set of imaging findings for the diagnosis of anthracosis.

Novel mutations and a severe neurological phenotype in Sjögren-Larsson syndrome patients from Iran.

Sjögren-Larsson syndrome (SLS) is a rare autosomal recessive disorder characterized by ichthyosis, spasticity and intellectual disability. The disease is caused by mutations in the ALDH3A2 gene that encodes fatty aldehyde dehydrogenase. We describe 7 Iranian SLS patients from 5 unrelated consanguineous families. Sequencing of ALDH3A2 identified 4 novel mutations, including a 26-bp deletion (c.25_50del), small in-frame deletion (c.370_372del; p.G124del), a termination (p.Q35Ter) and a missense mutation (p.Lys211Glu). Bacterial expression of the p.Lys211Glu and p.G124del mutations showed little or no detectable enzyme activity. Three of the patients exhibited an unusual neuro-regressive clinical course associated with seizures, which may reflect the presence of unidentified genetic or environmental modifiers in this consanguineous population. This cohort represents the largest group of Iranian patients with molecularly confirmed SLS and expands the mutational and clinical spectrum of this disease.

TOR1A variants cause a severe arthrogryposis with developmental delay, strabismus and tremor.

See Ginevrino and Valente (doi:10.1093/brain/awx260) for a scientific commentary on this article. Autosomal dominant torsion dystonia-1 is a disease with incomplete penetrance most often caused by an in-frame GAG deletion (p.Glu303del) in the endoplasmic reticulum luminal protein torsinA encoded by TOR1A. We report an association of the homozygous dominant disease-causing TOR1A p.Glu303del mutation, and a novel homozygous missense variant (p.Gly318Ser) with a severe arthrogryposis phenotype with developmental delay, strabismus and tremor in three unrelated Iranian families. All parents who were carriers of the TOR1A variant showed no evidence of neurological symptoms or signs, indicating decreased penetrance similar to families with autosomal dominant torsion dystonia-1. The results from cell assays demonstrate that the p.Gly318Ser substitution causes a redistribution of torsinA from the endoplasmic reticulum to the nuclear envelope, similar to the hallmark of the p.Glu303del mutation. Our study highlights that TOR1A mutations should be considered in patients with severe arthrogryposis and further expands the phenotypic spectrum associated with TOR1A mutations.

Neuroimaging findings of congenital Zika virus infection: a pictorial essay.

Zika virus (ZIKV) is a mosquito-borne arbovirus from the Flaviviridae family. It had caused several epidemics since its discovery in 1947, but there was no significant attention to this virus until the recent outbreak in Brazil in 2015. The main concern is the causal relationship between prenatal ZIKV infection and congenital microcephaly, which has been confirmed recently. Moreover, ZIKV may cause other central nervous system abnormalities such as brain parenchymal atrophy with secondary ventriculomegaly, intracranial calcification, malformations of cortical development (such as polymicrogyria, and lissencephaly-pachygyria), agenesis/hypoplasia of the corpus callosum, cerebellar and brainstem hypoplasia, sensorineural hearing-loss, and ocular abnormalities as well as arthrogryposis in the infected fetuses. Postnatal (acquired) ZIKV infection usually has an asymptomatic or mildly symptomatic course, while prenatal (congenital) ZIKV infection has a more severe course and may cause severe brain anomalies that are described as congenital Zika syndrome. In this pictorial essay, we aim to illustrate the prenatal and postnatal neuroimaging findings that may be seen in fetuses and neonates with congenital Zika syndrome, and will discuss possible radiological differential diagnoses. A detailed knowledge of these findings is paramount for an early correct diagnosis, prognosis determination, and counseling of the affected children and families.

Neuroimaging findings of Zika virus infection: a review article.

Zika virus (ZIKV) is an arbovirus from the Flaviviridae family. It is usually transmitted by mosquito bite. There have been no reports of severe symptoms caused by ZIKV infection up until the last few years. In October 2013 an outbreak was reported in French Polynesia with severe neurological complications in some affected cases. In November 2015, the Ministry of Health of Brazil attributed the increased number of neonatal microcephaly cases in northeastern Brazil to congenital ZIKV infection. The rapid spread of the virus convinced the World Health Organization to announce ZIKV infection as a "Public Health Emergency of International Concern" in February 2016. The main neuroimaging findings in congenital ZIKV infection include microcephaly which is the hallmark of the disease, other malformations of cortical development (e.g., lissencephaly, heterotopia, etc.), parenchymal calcifications, unilateral or bilateral ventriculomegaly, enlarged extra-axial CSF spaces, dysgenesis of the corpus callosum, agenesis of the cavum septum pellucidum, cerebellar and brainstem hypoplasia, and ocular abnormalities. ZIKV infection may also cause Guillain-Barré syndrome and acute disseminated encephalomyelitis in adults. Familiarity with neuroimaging findings of congenital and acquired ZIKV infection is crucial to suspect this disease in residents of endemic regions and travelers to these areas.

Soft X-ray absorption spectroscopy of Ar2 and ArNe dimers and small Ar clusters.

The X-ray absorption spectra (XAS) of Ar2 and ArNe dimers and small Ar clusters in the L2,3 region (244-252 eV) of the Ar atom have been recorded using synchrotron light and a combination of coincidence methods and kinetic energy discrimination of energetic ions. The absorption peaks in the spectra of the dimers and clusters were found to be shifted and broadened relative to the peaks in the spectrum of the Ar atom. In order to unambiguously relate these chemical shifts to the electronic structure of the core excited states in dimers, we performed ab initio calculations of the XAS spectra. Implications of the results for the use of XAS as a structure determination method in large rare gas clusters are discussed.

Metastable excited states of OBr2- and OCl2- dianions.

Electronic stabilities, structures, properties, and spectroscopic constants of the halogen oxide dianions OBr2- and OCl2- and their singly charged anions which are of astrophysical and laboratory interests have been studied. The X2Σ states of OBr2- and OCl2- are metastable with PECs having smooth wells with minima located at R=1.859 Å and 1.776 Å, and Coulomb barriers of 40402.54987 cm(-1) and 43746.63462 cm(-1) heights located at RRCB=2.100 Å and 1.922 Å, respectively, both without any vibrational states. While, the B2Σ state of OBr2- and the A2Σ state of OCl2- are metastable with PECs having wells deep enough to suite several bound states, with minima located at Re=1.773 Å and 1.6430 Å, and Coulomb barriers of 191437.45813 cm(-1) and 180550.70294 cm(-1) heights located at RRCB=2.658 Å and 2.4480 Å, with De=1.26470 eV and 1.60837 eV, respectively. The OBr- and OCl- singly charged anions are stable in their ground states. Based on the calculated Frank-Condon factors, it is concluded that metastable excited state OBr2- and OCl2- dianions and ground state OBr- and OCl- singly charged anions can be formed via electron capture processes.

Ground and excited states of the diatomic dianion Cl2(2-).

The QCISD(T)/aug-cc-pVQZ and CIS/aug-cc-pVQZ calculations have been carried out to obtain potential energy curves (PECs) of the Cl2(2-) diatomic dianion in order to address possibility of its formation in the merged beam fragmentation of Cl2(-) questioned based on the observation of the Cl(-)+Cl+e(-) channel. Results show that two of the excited states, namely A(1)Σg and a(3)Σg are metastable with PECs having wells deep enough to suite several bound states, with minima located at Re=2.8280 Å and Re=2.5972 Å, and Coulomb barriers of 1648.288 and 1403.835 cm(-1) heights located at 4.0320 and 3.6130 Å, respectively. Transition probabilities and tunneling predissociation lifetimes corresponding to these metastable states are also calculated and analyzed. Ground state X(1)Σg and excited states B(1)Σu, C(1)Πg and D(1)Πu calculated for this dianion are all repulsive. Calculated Franck-Condon factors suggest that Cl2(2-) can be produced in its excited states via an electron impact process initiating from the ground states of Cl2 and Cl2(-) .

Clinical features and severity of psoriasis: a comparison of facial and nonfacial involvement in Iran.

BACKGROUND: Facial involvement in psoriasis is accomplished with poor prognosis. In this study, clinical features and severity of psoriasis were compared between facial and nonfacial psoriasis involvement groups in Iran. It also evaluated these characteristics in different subtypes of facial psoriasis. METHODS: One hundred and thirty- eight psoriatic patients having referred to our clinic entered in this cross- sectional study in 2006 - 2007. Medical information, whole body and scalp Psoriasis Area and Severity Index (PASI) scores were obtained. Variables were compared between the facial and nonfacial involvement groups and also in different subtypes of the former including peripherofacial (PF), centrofacial (CF), and mixedfacial (MF). A P-value of < 0.05 was considered as significant. RESULTS: We found 55.0% facial involvement in Iranian psoriatic patients. MF (52.6%), CF (28.9%), and PF (18.4%), respectively were the common forms of facial involvement. The median whole body and scalp PASI scores, the number of male participants, and tongue involvement were significantly higher in patients with facial involvement. Comparing different subtypes of facial psoriasis, whole body PASI and scalp PASI scores were significantly higher in MF subtype and lower in CF subtype. Despite the least severity in the latter subtype, psoriatic arthritis and geographic tongue were shown to be more common in this subtype. Moreover, relapse history was correlated with PF subtype. CONCLUSIONS: Facial involvement in psoriasis had significantly higher whole body and scalp PASI scores in Iran which may be an indication of more severe disease. This difference was more prominent in MF subtype.