Recessive DES cardio/myopathy without myofibrillar aggregates: intronic splice variant silences one allele leaving only missense L190P-desmin.

We establish autosomal recessive DES variants p.(Leu190Pro) and a deep intronic splice variant causing inclusion of a frameshift-inducing artificial exon/intronic fragment, as the likely cause of myopathy with cardiac involvement in female siblings. Both sisters presented in their twenties with slowly progressive limb girdle weakness, severe systolic dysfunction, and progressive, severe respiratory weakness.

Kufs disease due to mutation of CLN6: clinical, pathological and molecular genetic features.

Kufs disease is the major adult form of neuronal ceroid lipofuscinosis, but is rare and difficult to diagnose. Diagnosis was traditionally dependent on the demonstration of characteristic storage material, but distinction from normal age-related accumulation of lipofuscin can be challenging. Mutation of CLN6 has emerged as the most important cause of recessive Kufs disease but, remarkably, is also responsible for variant late infantile ceroid lipofuscinosis.

Anncaliia algerae Microsporidial Myositis, New South Wales, Australia.

We describe the successful management of Anncaliia algerae microsporidial myositis in a man with graft versus host disease after hemopoietic stem cell transplantation. We also summarize clinical presentation and management approaches and discuss the importance of research into the acquisition of this infection and strategies for prevention.

Congenital Titinopathy: Comprehensive characterization and pathogenic insights.

Objective: Comprehensive clinical characterization of congenital titinopathy to facilitate diagnosis and management of this important emerging disorder.

Methods: Using massively parallel sequencing we identified 30 patients from 27 families with 2 pathogenic nonsense, frameshift and/or splice site TTN mutations in trans. We then undertook a detailed analysis of the clinical, histopathological and imaging features of these patients.

Nemaline myopathy and distal arthrogryposis associated with an autosomal recessive TNNT3 splice variant.

A male neonate presented with severe weakness, hypotonia, contractures and congenital scoliosis. Skeletal muscle specimens showed marked atrophy and degeneration of fast fibers with striking nemaline rods and hypertrophy of slow fibers that were ultrastructurally normal. A neuromuscular gene panel identified a homozygous essential splice variant in TNNT3 (chr11:1956150G > A, NM_006757.

A Recurrent De Novo Nonsense Variant in ZSWIM6 Results in Severe Intellectual Disability without Frontonasal or Limb Malformations.

A recurrent de novo missense variant within the C-terminal Sin3-like domain of ZSWIM6 was previously reported to cause acromelic frontonasal dysostosis (AFND), an autosomal-dominant severe frontonasal and limb malformation syndrome, associated with neurocognitive and motor delay, via a proposed gain-of-function effect. We present detailed phenotypic information on seven unrelated individuals with a recurrent de novo nonsense variant (c.2737C>T [p.

Variants in the Oxidoreductase PYROXD1 Cause Early-Onset Myopathy with Internalized Nuclei and Myofibrillar Disorganization.

This study establishes PYROXD1 variants as a cause of early-onset myopathy and uses biospecimens and cell lines, yeast, and zebrafish models to elucidate the fundamental role of PYROXD1 in skeletal muscle. Exome sequencing identified recessive variants in PYROXD1 in nine probands from five families. Affected individuals presented in infancy or childhood with slowly progressive proximal and distal weakness, facial weakness, nasal speech, swallowing difficulties, and normal to moderately elevated creatine kinase.

Neuronal deficiency of ARV1 causes an autosomal recessive epileptic encephalopathy.

We report an individual who presented with severe neurodevelopmental delay and an intractable infantile-onset seizure disorder. Exome sequencing identified a homozygous single nucleotide change that abolishes a splice donor site in the ARV1 gene (c.294 + 1G > A homozygous).

Recessive ACTA1 variant causes congenital muscular dystrophy with rigid spine.

Variants in ACTA1, which encodes α-skeletal actin, cause several congenital myopathies, most commonly nemaline myopathy. Autosomal recessive variants comprise approximately 10% of ACTA1 myopathy. All recessive variants reported to date have resulted in loss of skeletal α-actin expression from muscle and severe weakness from birth.

Anncaliia algerae microsporidial myositis.

The insect microsporidian Anncaliia algerae was first described in 2004 as a cause of fatal myositis in an immunosuppressed person from Pennsylvania, USA. Two cases were subsequently reported, and we detail 2 additional cases, including the only nonfatal case. We reviewed all 5 case histories with respect to clinical characteristics, diagnosis, and management and summarized organism life cycle and epidemiology.

Transurethral prostate resection in patients with hypocontractile detrusor--what is the predictive value of ultrastructural detrusor changes?

Purpose: Men with detrusor failure and chronic urinary retention have a lower voiding success rate and higher postoperative morbidity following transurethral prostatectomy than those with bladder outlet obstruction. Current investigations, including urodynamics, may be unable to predict the response to surgical treatment. We identified ultrastructural features on detrusor biopsy that correlated with the postoperative voiding outcome in patients with a hypocontractile detrusor undergoing transurethral prostatectomy.

Burns, biofilm and a new appraisal of burn wound sepsis.

Purpose: Following a burn, the wound may become colonized and septic complications may ensue. Many organisms, commonly isolated from burn wounds produce biofilms, which are defined as a collection of organisms on a surface surrounded by a matrix. Biofilms are associated with development of antibiotic resistant organisms and are refractory to the immune system.

Inhibition of tetraphenylphosphonium-induced NMR-visible lipid accumulation in human breast cells by chlorpromazine.

The effects of chlorpromazine (CPZ) on the lipid accumulation induced by the cationic lipophilic compound tetraphenylphosphonium chloride (TPP) were examined using proton nuclear magnetic resonance spectroscopy (NMR), lipid extraction and thin layer chromatography (TLC), and electron microscopy (EM). Chlorpromazine at concentrations of 12 or 25 microM significantly reduced the NMR-visible lipid accumulation induced by a 48-h treatment with 6.25 microM TPP in the human breast cell line, HBL-100, without affecting cell viability.

Tactile corpuscle-like bodies in colonic mucosa.

During the routine examination of a segment of colon resected for adenocarcinoma, a diffuse proliferation of mucosal tactile corpuscle-like bodies was identified. The bodies showed a lamellar structure by light microscopy and were S-100 positive. Electron microscopy demonstrated parallel slender processes with prominent surface caveolae, arising from peripheral cell bodies.

Nuclear magnetic resonance-visible lipids induced by cationic lipophilic chemotherapeutic agents are accompanied by increased lipid droplet formation and damaged mitochondria.

Proton nuclear magnetic resonance (NMR) spectroscopy, histological lipid staining, and electron microscopy were used to assess the biochemical and structural changes induced by treating the cultured human breast cell line HBL-100 with the cationic lipophilic phosphonium salts p-(triphenylphosphoniummethyl) benzaldehyde chloride (drug A) and [4-(hydrazinocarboxy)-1-butyl] tris-(4-dimethylaminophenyl) phosphonium chloride (drug B). The major biochemical change detected by (1)H NMR in drug-treated cells was a significant time- and concentration-dependent increase in lipid acyl chain resonances arising from mobile lipids. The amount of NMR-visible lipid strongly correlated with morphometric measurements of oil red O-staining lipid detected in the cytoplasm by light microscopy.