Planetary period magnetic field oscillations in Saturn's magnetosphere: Postequinox abrupt nonmonotonic transitions to northern system dominance

[1] We examine the “planetary period” magnetic field oscillations observed in the “core” region of Saturn's magnetosphere (dipole L ≤ 12), on 56 near‐equatorial Cassini periapsis passes that took place between vernal equinox in August 2009 and November 2012. Previous studies have shown that these consist of the sum of two oscillations related to the northern and southern polar regions having differing amplitudes and periods that had reached near‐equal amplitudes and near‐converged periods ~10.68 h in the interval to ~1 year after equinox. The present analysis shows that an interval of strongly differing behavior then began ~1.5 years after equinox, in which abrupt changes in properties took place at ~6‐ to 8‐month intervals, with three clear transitions occurring in February 2011, August 2011, and April 2012, respectively. These are characterized by large simultaneous changes in the amplitudes of the two systems, together with small changes in period about otherwise near‐constant values of ~10.63 h for the northern system and ~10.69 h for the southern (thus, not reversed postequinox) and on occasion jumps in phase. The first transition produced a resumption of strong southern system dominance unexpected under northern spring conditions, while the second introduced comparably strong northern system dominance for the first time in these data. The third resulted in suppression of all core oscillations followed by re‐emergence of both systems on a time scale of ~85 days, with the northern system remaining dominant but not as strongly as before. This behavior poses interesting questions for presently proposed theoretical scenarios

Additional file 5: Table S1. of Exploration of hydroxymethylation in Kagami-Ogata syndrome caused by hypermethylation of imprinting control regions

Six probes with high Δβ values only in brain tissue. (XLSX 45.1 kb

Additional file 7: Figure S5. of Exploration of hydroxymethylation in Kagami-Ogata syndrome caused by hypermethylation of imprinting control regions

Gel electropherograms showing appropriate digestion pattern of spike-in controls. (PPB 3.31 mb

Additional file 1: of Congenital limb deficiency in Japan: a cross-sectional nationwide survey on its epidemiology

Numbers of Total, Surveyed, and Responded Departments, and Breakdown of Responded Departments by Numbers of Reported Patients. This is the raw data used in the first survey of this study. (XLSX 12 kb

Molecular and clinical studies in 84 patients with pseudohypoparathyroidism type 1B

We conducted epigenotype-phenotype analysis in 84 patients with methylation defects of the DMRs on the GNAS locus classified into three groups according to the etiologies and methylation defect patterns of the DMRs on the GNAS locus.  </p

A case of siblings with juvenile retinitis pigmentosa associated with <i>NEK1</i> gene variants

Axial spondylometaphyseal dysplasia(axial SMD) is associated with early-onset retinal dystrophy and various skeletal dysplasias of varying severity. NEK1 is the causative gene for short rib polydactyly syndrome and axial SMD. Here, we report a case of siblings with juvenile retinitis pigmentosa (RP) and NEK1 variants not associated with systemic disorders. The patients were a 7-year-old-girl and a 9-year-old boy with RP, who were followed for 9 years. Whole exome sequencing (WES) was performed on the siblings and their parents, who were not consanguineous. The corrected visual acuity of the girl and the boy at first visit was binocular 20/63 and 20/100 OD and 20/63 OS, respectively. The siblings had narrowing of retinal blood vessels and retinal pigment epithelium atrophy in the fundus and showed an extinguished pattern in electroretinogram. On optical coherence tomography, there was a mottled ellipsoid band with progressive loss in the outer macular, the edges of which corresponded to the ring of hyperautofluorescence on fundus autofluorescence imaging. The siblings showed progressive visual field constriction. Radiological examination did not reveal any skeletal abnormalities. We identified two rare heterozygous NEK1 variants in the patients: c.240 G>A; p.(M80I) and c.634_639dup;p.(V212_L213dup). Heterozygous variants were recognized in the father and mother, respectively. According to the guidelines of the American College of Medical Genetics and Genomics, both variants were classified as likely pathogenic. This is the first report of RP patients with NEK1 variants not associated with skeletal abnormalities.</p

<i>TBX1</i> Mutation Identified by Exome Sequencing in a Japanese Family with 22q11.2 Deletion Syndrome-Like Craniofacial Features and Hypocalcemia

<div><p>Background</p><p>Although <i>TBX1</i> mutations have been identified in patients with 22q11.2 deletion syndrome (22q11.2DS)-like phenotypes including characteristic craniofacial features, cardiovascular anomalies, hypoparathyroidism, and thymic hypoplasia, the frequency of <i>TBX1</i> mutations remains rare in deletion-negative patients. Thus, it would be reasonable to perform a comprehensive genetic analysis in deletion-negative patients with 22q11.2DS-like phenotypes.</p><p>Methodology/Principal Findings</p><p>We studied three subjects with craniofacial features and hypocalcemia (group 1), two subjects with craniofacial features alone (group 2), and three subjects with normal phenotype within a single Japanese family. Fluorescence <i>in situ</i> hybridization analysis excluded chromosome 22q11.2 deletion, and genomewide array comparative genomic hybridization analysis revealed no copy number change specific to group 1 or groups 1+2. However, exome sequencing identified a heterozygous <i>TBX1</i> frameshift mutation (c.1253delA, p.Y418fsX459) specific to groups 1+2, as well as six missense variants and two in-frame microdeletions specific to groups 1+2 and two missense variants specific to group 1. The <i>TBX1</i> mutation resided at exon 9C and was predicted to produce a non-functional truncated protein missing the nuclear localization signal and most of the transactivation domain.</p><p>Conclusions/Significance</p><p>Clinical features in groups 1+2 are well explained by the <i>TBX1</i> mutation, while the clinical effects of the remaining variants are largely unknown. Thus, the results exemplify the usefulness of exome sequencing in the identification of disease-causing mutations in familial disorders. Furthermore, the results, in conjunction with the previous data, imply that <i>TBX1</i> isoform C is the biologically essential variant and that <i>TBX1</i> mutations are associated with a wide phenotypic spectrum, including most of 22q11.2DS phenotypes.</p></div

<i>TBX1</i> mutation identified in this family.

<p><b>A.</b> Genomic structure of <i>TBX1</i> and the position of the mutation. The color and the white boxes represent the coding regions and the untranslated regions on exons 1–10 (E1–E10), respectively; the red, the purple, and the orange segments indicate the coding regions on the final exons 9C, 9A, and 9B (splice variants), respectively. The T-box is indicated by yellow boxes, the nuclear localization signal (NLA) by a blue segment, and the transactivation domain (TAD) by a green arrow. The c.1253delA (p.Y418fsX459) identified in this family resides on exon 9C. <b>B.</b> Transcripts of <i>TBX1</i>. Three variants are formed by alternative splicing of the final exons 9C, 9A, and 9B. The c.1253delA (p.Y418fsX459) mutation is predicted to yield a truncated TBX1C protein missing the NLS and most of the TAD. The stippled box of p.Y418fsX459 denotes aberrant amino acid sequence produced by the frameshift mutation. <b>C.</b> Electrochromatograms showing the frameshift mutation by Sanger sequencing. The primer sequences used are: 5′-GCGGCCAAGAGCCTTCTCT-3′ and 5′-GGGTGGTAGCCGTGGCCA-3′.</p

Clinical and laboratory findings of cases 1–3.

<p>DSD, disorders of sex development; MP, micropenis; HS, hypospadias; CO, cryptorchidism.</p><p>The hormone values below the reference range are boldfaced, and those above the reference range are italicized.</p>a<p>Reference values of the age-matched control individuals are shown in the parenthesis.</p

The pedigree of this family.

<p>Facial features of subjects III-5 and III-7 are shown.</p