Prenatal Coffin-Siris Syndrome: Expanding the Phenotypic and Genotypic Spectrum of the Disease.

Coffin-Siris syndrome is an autosomal dominant disorder with neurological, cardiovascular, and gastrointestinal symptoms. Patients with Coffin-Siris syndrome typically have variable degree of developmental delay or intellectual disability, muscular hypotonia, dysmorphic facial features, sparse scalp hair, but otherwise hirsutism and fifth digit nail or distal phalanx hypoplasia or aplasia. Coffin-Siris syndrome is caused by pathogenic variants in 12 different genes including and .

Study protocol for a randomized controlled trial with rituximab for psychotic disorder in adults (RCT-Rits).

Background: The role of inflammation in the aetiology of schizophrenia has gained wide attention and research on the association shows an exponential growth in the last 15 years. Autoimmune diseases and severe infections are risk factors for the later development of schizophrenia, elevated inflammatory markers in childhood or adolescence are associated with a greater risk of schizophrenia in adulthood, individuals with schizophrenia have increased levels of pro-inflammatory cytokines compared to healthy controls, and autoimmune diseases are overrepresented in schizophrenia. However, treatments with anti-inflammatory agents are so far of doubtful clinical relevance.

Overlap between EEC and AEC syndrome and immunodeficiency in a preterm infant with a TP63 variant.

Pathogenic variants in the transcription factor TP63 gene cause a variety of clinical phenotypes, such as ectrodactyly-ectodermal dysplasia-clefting (EEC) syndrome and ankyloblepharon-ectodermal dysplasia-clefting (AEC) syndrome. Historically, TP63-related phenotypes have been divided into several syndromes based on both the clinical presentation and location of the pathogenic variant on the TP63 gene. This division is complicated by significant overlap between syndromes.

Efficacy and Safety of Rituximab for New-Onset Generalized Myasthenia Gravis: The RINOMAX Randomized Clinical Trial.

Importance: Rituximab is a third-line option for refractory generalized myasthenia gravis (MG) based on empirical evidence, but its effect in new-onset disease is unknown.

Objective: To investigate the efficacy and safety of rituximab compared with placebo as an add-on to standard of care for MG.

Design, Setting, And Participants: This randomized, double-blind, placebo-controlled study took place throughout 48 weeks at 7 regional clinics in Sweden.

Dissimilar Laser Welding of Austenitic Stainless Steel and Abrasion-Resistant Steel: Microstructural Evolution and Mechanical Properties Enhanced by Post-Weld Heat Treatment.

In this study, ultra-high-strength steels, namely, cold-hardened austenitic stainless steel AISI 301 and martensitic abrasion-resistant steel AR600, as base metals (BMs) were butt-welded using a disk laser to evaluate the microstructure, mechanical properties, and effect of post-weld heat treatment (PWHT) at 250 °C of the dissimilar joints. The welding processes were conducted at different energy inputs (EIs; 50-320 J/mm). The microstructural evolution of the fusion zones (FZ) in the welded joints was examined using electron backscattering diffraction (EBSD) and laser scanning confocal microscopy.

Novel germline variant in the histone demethylase and transcription regulator KDM4C induces a multi-cancer phenotype.

Background: Genes involved in epigenetic regulation are central for chromatin structure and gene expression. Specific mutations in these might promote carcinogenesis in several tissue types.

Methods: We used exome, whole-genome and Sanger sequencing to detect rare variants shared by seven affected individuals in a striking early-onset multi-cancer family.

Wilson's Disease in Finland: A Nationwide Population-Based Study.

Background: Data on the epidemiology and prognosis of Wilson's disease are scarce, and no clinical data are available from Finland.

Methods: All persons diagnosed and treated for Wilson's disease in Finnish hospitals in 1998 to 2017 were identified. Data were collected from national registries and patient charts.

Diagnostic accuracy of intrathecal kappa free light chains compared with OCBs in MS.

Objective: To determine what kappa free light chain (KFLC) metric has the highest capacity to separate healthy patients from patients with MS, we evaluated the sensitivity, specificity, and the overall diagnostic accuracy of 4 different KFLC metrics. To assess the usefulness of KFLC in the diagnostics of MS, we compared the different KFLC metrics with oligoclonal bands (OCBs), the current gold standard biochemical method to demonstrate intrathecal antibody production.

Methods: CSF and plasma were collected from patients with confirmed or suspected MS, other neurological diseases, as well as symptomatic and healthy controls between May 2017 and May 2018 (n = 335) at the Department of Neurology, Karolinska University Hospital, as part of routine diagnostic workup.

Comparison Between Rituximab Treatment for New-Onset Generalized Myasthenia Gravis and Refractory Generalized Myasthenia Gravis.

Importance: Use of biologic agents in generalized myasthenia gravis is generally limited to therapy-refractory cases; benefit in new-onset disease is unknown.

Objective: To assess rituximab in refractory and new-onset generalized myasthenia gravis and rituximab vs conventional immunotherapy in new-onset disease.

Design, Setting, And Participants: A retrospective cohort study with prospectively collected data was conducted on a county-based community sample at Karolinska University Hospital, Stockholm, Sweden.

Retinal nerve fiber layer thickness associates with cognitive impairment and physical disability in multiple sclerosis.

Background: Reductions of the peripapillary retinal nerve fiber layer (pRNFL) thickness has been indicated even in early-stages of multiple sclerosis (MS). The aim was to investigate the association between pRNFL thickness, measured with optical coherence tomography (OCT), and physical disability and cognitive impairment in MS.

Methods: 465 MS patients and 168 healthy controls (HCs) were included.

Successful combined treatment with thymectomy, rituximab and tocilizumab for severe thymoma-associated multi autoimmune syndrome.

We present a 53-year-old woman who presented simultaneously with acute inflammatory demyelinating polyneuropathy, Graves' disease, leukocytoclastic vasculitis, elevated acetylcholine antibody receptor antibodies and a mediastinal mass. Thymectomy was performed and revealed a type A thymoma and the clinical picture and paraclinical findings were consistent with a thymoma-associated multi-autoimmune syndrome (TAMA). Beside prednisolone and plasmapheresis, the patient was treated with tocilizumab and rituximab.

HTT haplogroups in Finnish patients with Huntington disease.

Objective: To study genetic causes of the low frequency of Huntington disease (HD) in the Finnish population, we determined haplogroups in the population and patients with HD and analyzed intergenerational Cytosine-Adenosine-Guanosine (CAG) stability.

Methods: A national cohort of patients with HD was used to identify families with mutant . haplogroups were determined in 225 archival samples from patients and from 292 population samples.

Hypomorphic mutations of TRIP11 cause odontochondrodysplasia.

Odontochondrodysplasia (ODCD) is an unresolved genetic disorder of skeletal and dental development. Here, we show that ODCD is caused by hypomorphic TRIP11 mutations, and we identify ODCD as the nonlethal counterpart to achondrogenesis 1A (ACG1A), the known null phenotype in humans. TRIP11 encodes Golgi-associated microtubule-binding protein 210 (GMAP-210), an essential tether protein of the Golgi apparatus that physically interacts with intraflagellar transport 20 (IFT20), a component of the ciliary intraflagellar transport complex B.

Neuromyelitis optica spectrum disorder with increased aquaporin-4 microparticles prior to autoantibodies in cerebrospinal fluid: a case report.

Background: Neuromyelitis optica spectrum disorders are severe autoimmune inflammatory diseases of the central nervous system associated with the presence of immunoglobulin G antibodies against the water channel protein aquaporin-4. During exacerbation, specific aquaporin-4 immunoglobulin G may be produced intrathecally. We measured extracellular aquaporin-4 microparticles in the cerebrospinal fluid of a patient who later developed the typical symptoms and signs of a neuromyelitis optica spectrum disorder.

Potential of municipal solid waste paper as raw material for production of cellulose nanofibres.

When aiming for higher resource efficiency, greater utilization of waste streams is needed. In this work, waste paper separated from mixed municipal solid waste (MSW) was studied as a potential starting material for the production of cellulose nanofibres (CNFs). The waste paper was treated using three different techniques, namely pulping, flotation and washing, after which it was subjected to an ultrafine grinding process to produce CNFs.

A 69-year-old woman with Coffin-Siris syndrome.

Coffin-Siris syndrome (CSS) is a rare intellectual disability syndrome classically characterized by aplasia or hypoplasia of the distal phalanx or nail of the fifth and other digits, distinctive facial features, hirsutism/hypertrichosis, and sparce scalp hair. It is genetically heterogeneous but most often caused by a pathogenic variant in the ARID1B gene. Previous clinical reports of CSS patients are mainly based on young or middle-aged individuals.

The Temporal Retinal Nerve Fiber Layer Thickness Is the Most Important Optical Coherence Tomography Estimate in Multiple Sclerosis.

Background: Reduced peripapillary retinal nerve fiber layer (pRNFL) and combined ganglion cell and inner plexiform layer (GCIP) thicknesses as measured by optical coherence tomography (OCT) have been observed in multiple sclerosis (MS) patients. The purpose was to determine the most associative OCT measure to level of cognitive and physical disability in MS.

Methods: Data were collected from 546 MS patients and 175 healthy controls (HCs).

A homozygous mutation underlies a familial case of non-syndromic primary ovarian insufficiency.

Primary Ovarian Insufficiency (POI) affects ~1% of women under forty. Exome sequencing of two Finnish sisters with non-syndromic POI revealed a homozygous mutation in leading to a truncated protein (p.Gln1701*).

Heroin-induced acute myelopathy with extreme high levels of CSF glial fibrillar acidic protein indicating a toxic effect on astrocytes.

A man aged 33 years with previous heroin substance abuse was found unconscious lying in a bush. The patient had been without heroin for some time but had just started to use intravenous heroin again, 0.5-2 g daily.

Food allergy in a child with de novo mutation.

Crying combined with miscellaneous gastrointestinal symptoms are typical symptoms of infant with food allergy, but are also common among children with abnormal neurological development. Mutations in gene is known to cause a syndrome characterized by developmental delay, hypotonia, cardiac defects, microcephaly, specific facial features and early feeding problems. However, these feeding problems have not earlier been specified.

TSC2 c.1864C>T variant associated with mild cases of tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) is an autosomal dominantly inherited disorder with variable expressivity associated with hamartomatous tumors, abnormalities of the skin, and neurologic problems including seizures, intellectual disability, and autism. TSC is caused by pathogenic variants in either TSC1 or TSC2. In general, TSC2 pathogenic variants are associated with a more severe phenotype than TSC1 pathogenic variants.

SNCA mutation p.Ala53Glu is derived from a common founder in the Finnish population.

Mutations in SNCA are rare causes of familial Parkinson's disease (PD). We have previously described a novel p.Ala53Glu mutation in 2 Finnish families.

Clinical and imaging findings in Parkinson disease associated with the A53E SNCA mutation.

Objective: To describe the clinical features and brain imaging findings of autosomal dominant Parkinson disease (PD) associated with a recently reported mutation in SNCA.

Methods: A Finnish family with PD in 3 successive generations, in accordance with an autosomal dominant inheritance pattern, was identified. We examined 2 available members of the family, the female proband and her daughter (both with early-onset PD), clinically and using dopamine transporter imaging ([(123)I]FP-CIT SPECT).

[Parkinson's disease associated with a mutation in the PARK2 gene].

The most common cause of monogenic hereditary Parkinson's disease is a mutation in the PARK2 gene. Early onset, slow progression, dystonia, and good response to levodopa are typical of the disease phenotype. Finnish PARK2 patients have not been described previously.

Epidemiology of Huntington's disease in Finland.

Object: To estimate the prevalence of Huntington's disease (HD) in Finland.

Methods: Persons diagnosed with HD from 1987 to 2010 were identified in the national registers and hospital records of the identified patients, and death certificates of the deceased subjects were obtained. Results of genetic analyses were obtained from the two national laboratories.