Newborn Screening for X-Linked Adrenoleukodystrophy in Nebraska: Initial Experiences and Challenges.

X-linked adrenoleukodystrophy (X-ALD) is a neurodegenerative disease caused by pathogenic variants in resulting in defective peroxisomal oxidation of very long-chain fatty acids. Most male patients develop adrenal insufficiency and one of two neurologic phenotypes: a rapidly progressive demyelinating disease in mid-childhood (childhood cerebral X-ALD, ccALD) or an adult-onset spastic paraparesis (adrenomyeloneuropathy, AMN). The neurodegenerative course of ccALD can be halted if patients are treated with hematopoietic stem cell transplantation at the earliest onset of white matter disease.

Disruption of , encoding delta-catenin, causes a penetrant attention deficit disorder and myopia.

Attention deficit hyperactivity disorder (ADHD) is a common and highly heritable neurodevelopmental disorder with poorly understood pathophysiology and genetic mechanisms. A balanced chromosomal translocation interrupts in several members of a family with profound attentional deficit and myopia, and disruption of the gene was found in a separate unrelated individual with ADHD and myopia. encodes a brain-specific member of the adherens junction complex essential for postsynaptic and dendritic development, a site of potential pathophysiology in attentional disorders.

The iron-sulphur cluster in human DNA2 is required for all biochemical activities of DNA2.

The nuclease/helicase DNA2 plays important roles in DNA replication, repair and processing of stalled replication forks. DNA2 contains an iron-sulphur (FeS) cluster, conserved in eukaryotes and in a related bacterial nuclease. FeS clusters in DNA maintenance proteins are required for structural integrity and/or act as redox-sensors.

PIGQ glycosylphosphatidylinositol-anchored protein deficiency: Characterizing the phenotype.

PIGQ (OMIM *605754) encodes phosphatidylinositol glycan biosynthesis class Q (PIGQ) and is required for proper functioning of an N-acetylglucosamine transferase complex in a similar manner to the more established PIGA, PIGC, and PIGH. There are two previous patients reported with homozygous and apparently deleterious PIGQ mutations. Here, we provide the first detailed clinical report of a patient with heterozygous deleterious mutations associated with glycosylphosphatidylinositol-anchored protein (GPI-AP) biosynthesis deficiency.

Structural brain anomalies in patients with FOXG1 syndrome and in Foxg1+/- mice.

Objective: FOXG1 syndrome is a rare neurodevelopmental disorder associated with heterozygous variants or chromosomal microaberrations in 14q12. The study aimed at assessing the scope of structural cerebral anomalies revealed by neuroimaging to delineate the genotype and neuroimaging phenotype associations.

Methods: We compiled 34 patients with a heterozygous (likely) pathogenic variant.

Novel Mutations Identified With Next-Generation Sequencing Expand the Spectrum of PLP1-Associated Leukodystrophy Clinical Phenotypes.

Next-generation sequencing was performed for 2 families with an undiagnosed neurologic disease. Analysis revealed X-linked mutations in the () gene, which is associated with X-linked Pelizaeus-Merzbacher disease and Spastic Paraplegia type 2. In family A, the novel missense mutation c.

Capture-based high-coverage NGS: a powerful tool to uncover a wide spectrum of mutation types.

Purpose: Next-generation sequencing (NGS) has been widely applied to clinical diagnosis. Target-gene capture followed by deep sequencing provides unbiased enrichment of the target sequences, which not only accurately detects single-nucleotide variations (SNVs) and small insertion/deletions (indels) but also provides the opportunity for the identification of exonic copy-number variants (CNVs) and large genomic rearrangements.

Method: Capture NGS has the ability to easily detect SNVs and small indels.

Osteogenesis imperfecta caused by PPIB mutation with severe phenotype and congenital hearing loss.

Osteogenesis imperfecta (OI) is an inherited disorder of connective tissue typically caused by defects in either COL1A1 or COL1A2. A number of other genes causative of this disorder have been found, including PPIB, which forms one subunit of the prolyl 3-hydroxylase enzyme complex. Patients with homozygous or compound heterozygous mutations in this gene have OI with a trend toward lethal or severe phenotype.

Mode of action of diterpene and characterization of related metabolites from the soft coral, Xenia elongata.

Chemical and biological investigation of the cultured marine soft coral Xenia elongata led to the isolation of two new diterpenes (2, 3). Their structures were elucidated using a combination of NMR and mass spectrometry. Biological evaluations and assessments were determined using the specific apoptosis induction assay based on genetically engineered mammalian cell line D3 deficient in Bak and Bax and derived from a mouse epithelial cell.

Deep-sea hydrothermal vent Epsilonproteobacteria encode a conserved and widespread nitrate reduction pathway (Nap).

Despite the frequent isolation of nitrate-respiring Epsilonproteobacteria from deep-sea hydrothermal vents, the genes coding for the nitrate reduction pathway in these organisms have not been investigated in depth. In this study we have shown that the gene cluster coding for the periplasmic nitrate reductase complex (nap) is highly conserved in chemolithoautotrophic, nitrate-reducing Epsilonproteobacteria from deep-sea hydrothermal vents. Furthermore, we have shown that the napA gene is expressed in pure cultures of vent Epsilonproteobacteria and it is highly conserved in microbial communities collected from deep-sea vents characterized by different temperature and redox regimes.

Variability of disease spectrum in children with liver phosphorylase kinase deficiency caused by mutations in the PHKG2 gene.

Liver phosphorylase b kinase (PhK) deficiency (glycogen storage disease type IX), one of the most common causes of glycogen storage disease, is caused by mutations in the PHKA2, PHKB, and PHKG2 genes. Presenting symptoms include hepatomegaly, ketotic hypoglycemia, and growth delay. Clinical severity varies widely.

Prevalence of pilomatricoma in Turner syndrome: findings from a multicenter study.

Importance: The absence of data on the prevalence of pilomatricoma among patients with Turner syndrome served as the catalyst for this multicenter investigation.

Objectives: To ascertain the prevalence of pilomatricoma among patients with Turner syndrome and to determine any association between the development of pilomatricomas and the use of exogenous hormones in patients with Turner syndrome.

Design: A retrospective medical record review from January 1, 2000, through January 1, 2010, was performed of all patients with Turner syndrome.

Ammonificins C and D, hydroxyethylamine chromene derivatives from a cultured marine hydrothermal vent bacterium, Thermovibrio ammonificans.

Chemical and biological investigation of the cultured marine hydrothermal vent bacterium, Thermovibrio ammonifican led to the isolation of two hydroxyethylamine chromene derivatives, ammonificins C and D. Their structures were elucidated using combination of NMR and mass spectrometry. Absolute stereochemistry was ascertained by comparison of experimental and calculated CD spectra.

Evaluation and comparison of safety, convenience and cost of administering intravenous pamidronate infusions to children in the home and ambulatory care settings.

The use of bisphosphonates in children to treat low bone mineral density has increased. Safety and efficacy of pamidronate has been previously demonstrated. However, little research has been done on pamidronate infusion in the home health setting for patients with metabolic bone disease.

Enzyme-replacement therapy in life-threatening hypophosphatasia.

Background: Hypophosphatasia results from mutations in the gene for the tissue-nonspecific isozyme of alkaline phosphatase (TNSALP). Inorganic pyrophosphate accumulates extracellularly, leading to rickets or osteomalacia. Severely affected babies often die from respiratory insufficiency due to progressive chest deformity or have persistent bone disease.

Parvibaculum hydrocarboniclasticum sp. nov., a mesophilic, alkane-oxidizing alphaproteobacterium isolated from a deep-sea hydrothermal vent on the East Pacific Rise.

An aerobic, alkane-oxidizing bacterium, designated strain EPR92(T), was isolated from hydrothermal fluids that had been collected from a deep-sea vent on the East Pacific Rise (at 9° 50' N 104° 17' W). The cells of the novel strain were Gram-staining-negative rods that measured approximately 1.4 µm in length and 0.

Phorcysia thermohydrogeniphila gen. nov., sp. nov., a thermophilic, chemolithoautotrophic, nitrate-ammonifying bacterium from a deep-sea hydrothermal vent.

A novel hyperthermophilic, anaerobic, chemolithoautotrophic bacterium, designated strain HB-8(T), was isolated from the tube of Alvinella pompejana tubeworms collected from the wall of an actively venting sulfide structure on the East Pacific Rise at 13° N. The cells were Gram-negative rods, approximately 1.0-1.

The incidence of spondylolysis and spondylolisthesis in children with osteogenesis imperfecta.

Background: Spondylolysis and spondylolisthesis are common abnormalities of the lumbar spine. The incidence of these diagnoses is recognized in the healthy population. However, their incidence in osteogenesis imperfecta (OI) patients is less well defined.

Genetic diversity and demographic instability in Riftia pachyptila tubeworms from eastern Pacific hydrothermal vents.

Background: Deep-sea hydrothermal vent animals occupy patchy and ephemeral habitats supported by chemosynthetic primary production. Volcanic and tectonic activities controlling the turnover of these habitats contribute to demographic instability that erodes genetic variation within and among colonies of these animals. We examined DNA sequences from one mitochondrial and three nuclear gene loci to assess genetic diversity in the siboglinid tubeworm, Riftia pachyptila, a widely distributed constituent of vents along the East Pacific Rise and Galápagos Rift.

Bathymodiolamides A and B, ceramide derivatives from a deep-sea hydrothermal vent invertebrate mussel, Bathymodiolus thermophilus.

Two ceramide derivatives, bathymodiolamides A (1) and B (2), were isolated from the deep-sea hydrothermal vent invertebrate mussel Bathymodiolus thermophilus. The molecular structures of these compounds were determined using a combination of NMR spectroscopy, mass spectrometry, and chemical degradation. Biological activities were assessed in a ApopScreen cell-based screen for apoptosis induction and potential anticancer activity.

Ammonificins A and B, hydroxyethylamine chroman derivatives from a cultured marine hydrothermal vent bacterium, Thermovibrio ammonificans.

Two hydroxyethylamine chroman derivatives, ammonificins A (1) and B (2), were isolated from the marine hydrothermal vent bacterium Thermovibrio ammonificans. The molecular structures of these compounds were determined using a combination of NMR, mass spectrometry, and CD analyses. Biological activities were determined using an antimicrobial assay and the patented ApopScreen cell-based screen for apoptosis induction and potential anticancer activity.

Salinisphaera hydrothermalis sp. nov., a mesophilic, halotolerant, facultatively autotrophic, thiosulfate-oxidizing gammaproteobacterium from deep-sea hydrothermal vents, and emended description of the genus Salinisphaera.

A mesophilic, aerobic, facultatively chemolithoautotrophic bacterium, designated strain EPR70(T), was isolated from hydrothermal fluids from diffuse-flow vents on the East Pacific Rise at degrees 50' N 10 degrees 17' W. Cells were Gram-negative rods, approximately 0.8-1.