Familial cryptic translocation resulting in Angelman syndrome:implications for imprinting or location of the Angelman gene?

Angelman syndrome (AS) is associated with a loss of maternal genetic information, which typically occurs as a result of a deletion at 15q11-q13 or paternal uniparental disomy of chromosome 15. We report a patient with AS as a result of an unbalanced cryptic translocation whose breakpoint, at 15q11.2, falls within this region. The proband was diagnosed clinically as having Angelman syndrome, but without a detectable cytogenetic deletion, by using high-resolution G-banding. FISH detected a deletion of D15S11 (IR4-3R), with an intact GABRB3 locus. Subsequent studies of the proband's mother and sister detected a cryptic reciprocal translocation between chromosomes 14 and 15 with the breakpoint being between SNRPN and D15S10 (3- 21). The proband was found to have inherited an unbalanced form, being monosomic from 15pter through SNRPN and trisomic for 14pter to 14q11.2. DNA methylation studies showed that the proband had a paternal-only DNA methylation pattern at SNRPN, D15S63 (PW71), and ZNF127. The mother and unaffected sister, both having the balanced translocation, demonstrated normal DNA methylation patterns at all three loci. These data suggest that the gene for AS most likely lies proximal to D15S10, in contrast to the previously published position, although a less likely possibility is that the maternally inherited imprinting center acts in trans in the unaffected balanced translocation carrier sister.     

Woodland management at the Swedish middle Neolithic site of Alvastra? A new perspective

It is often argued that the repetitive removal of branches to improve the quantity and the quality of wood, i.e. woodland management, has been practiced in Europe from the Mesolithic and/or Neolithic onwards. The Neolithic pile dwelling of Alvastra in Sweden has been mentioned in textbooks as a classical example of this practice. The conclusion about woodland management at Alvastra was primarily based on palynological data, which do not provide any direct evidence. Is it correct to conclude that woodland management was practiced at Alvastra? To investigate that, this paper reviews the previous arguments and interpretations, focusing on wood data, and by comparing archaeological data with modern wood data. First, the assemblage of vertical posts from the latest excavations at Alvastra include a wide range of taxa, showing opportunistic use of the woody vegetation. Second, while the dendrochronological analysis of Quercus and Ulmus carried out in the 80 s has clearly indicated that the trees used for the posts grew under highly similar conditions and that particularly many Quercus trees started to grow more or less at the same time, the reason for the partially simultaneous start of growth remains unknown, and the posts used for the construction of the site do not provide evidence of repetitive removal of trunks from stools. Finally, analysis of the age/diameter data of the Corylus wood indicates the use of branches from unmanaged vegetation, while age data of Salix do not support management either. In conclusion, the data do not support the hypothesis of woodland management at Neolithic Alvastra, and it is most likely that people did not practice woodland management. This outcome corresponds to the conclusions in some of the previous publications about the site.

     

Angelman syndrome and hypothyroidism - coincidence or unique correlation?

Angelman Syndrome (AS, MIM 105830), classified among neurogenetic disorders, occurs with estimated frequency of 1:10 000 to 1:40 000. The characteristics features apart from neurodevelopmental impairment and seizures include peculiar face traits, absent speech, outburst of laughter, ataxia, stereotyped jerky (puppet-like) movements. The authors report three children with Angelman syndrome who were also diagnosed with hypothyroidism.     

What is targeted proteomics? A concise revision of targeted acquisition and targeted data analysis in mass spectrometry

Targeted proteomics has gained significant popularity in mass spectrometry‐based protein quantification as a method to detect proteins of interest with high sensitivity, quantitative accuracy and reproducibility. However, with the emergence of a wide variety of targeted proteomics methods, some of them with high‐throughput capabilities, it is easy to overlook the essence of each method and to determine what makes each of them a targeted proteomics method. In this viewpoint, we revisit the main targeted proteomics methods and classify them in four categories differentiating those methods that perform targeted data acquisition from targeted data analysis, and those methods that are based on peptide ion data (MS1 targeted methods) from those that rely on the peptide fragments (MS2 targeted methods).     

Haematemesis: a new syndrome?

Three patients presented with symptoms suggesting a Mallory-Weiss tear. Endoscopy showed a localized, clearly demarcated area of bright red mucosa near the gastro-oesophageal junction; this was thought to have arisen by retrograde intussusception of the stomach during vomiting or retching and may have caused the haemorrhage.     

RNA interference: new mechanisms for targeted treatment?

Nucleic acid-based sequence-specific therapeutic intervention offers the potential for treatment of particular cancers without side effects. RNA interference (RNAi) induced by small interfering RNA (siRNA) (19-21 bp) is a normal cellular mechanism leading to highly specific and extraordinarily efficient degradation of the corresponding mRNA. The mechanism of RNAi as well as strategies for the design and delivery of siRNA are described. The growing role of RNAi in target validation for cancer-specific genetic aberrations is discussed. We attempt an early assessment of the potential for using RNAi technologies to treat cancer directly, especially hematologic malignancies. Promising targets for specific gene silencing in hematologic oncology include oncogenic fusion proteins and oncogenes activated by point mutations. Potency and specificity of gene silencing are the major advantages of the new RNAi technology over other nucleic acid-based gene targeting approaches. Crucial questions for pharmaceutical interventions remain. Advances in the areas of delivery, systemic spreading and duration of the silencing effect are necessary before the methodology can enter clinical oncology.     

A variant example of familial Floating-Harbor syndrome?

The Floating-Harbor syndrome (FHS) is clinically characterized by short stature, retarded speech development, delayed bone age, typical facies, bulbous nose, wide columella, thin lips. Four cases with celiac disease have been described previously. In two other cases, autosomal dominant inheritance has been suggested. We describe a boy aged 2 years 11 months with clinical features of FHS and celiac disease. His mother also presents minor phenotypical characteristics, suggesting that the present observation corresponds to a variant example of familial FHS.     

A 5-kb imprinting center deletion in a family with Angelman syndrome reduces the shortest region of deletion overlap to 880 bp

Imprinting on human chromosome 15q11-q13 is controlled by a bipartite imprinting center (IC) that maps to the SNRPN locus. Deletions of the IC result in an imprinting defect and Prader-Willi syndrome or Angelman syndrome (AS). We have now identified a 5-kb IC deletion in an English AS patient (AS-LO); this represents the smallest microdeletion found in AS and narrows down the shortest region of deletion overlap to 880 bp.     

Hypoalbuminaemic hyponatraemia: a new syndrome?

Six patients with severe hyponatraemia had neurological features of hyponatraemia and pronounced hypoalbuminaemia. All had biochemical features typical of the syndrome of inappropriate secretion of antidiuretic hormone with low serum osmolality and an inappropriately high urinary osmolality. All were given infusions of whole plasma or albumin solution, or both, to restore their plasma albumin concentrations to normal, which led to a dramatic increase in plasma sodium concentrations and serum osmolality, with a concomitant fall in urinary osmolality in all patients. Neurological features were reversed in four patients. It is suggested that severe hypoalbuminaemia is an important cause of appreciable hyponatraemia; infusions of plasma and albumin in such patients may reverse the biochemical and clinical features and should form the basis of management.     

A survey of osteoderm histology and ornamentation among Crocodylomorpha: A new proxy to infer lifestyle?

Osteoderms of eight extant and extinct species of crocodylomorphs are studied histologically and morphologically. Most osteoderms display the typical “crocodilian” structure with a woven-fibered matrix surrounded by an upper and a lower parallel fibered matrix. The dorsal ornamentation of those specimens consists of a pit-and-ridge structure, with corresponding remodeling mechanisms. However, an osteoderm of Iberosuchus, studied here for the first time, differs in being nearly devoid of ornamentation; moreover, it shows strong bundles of straight Sharpey's fibers perpendicular to the surface in its lateral and dorsal walls, along with a rough plywood-like structure in its basal plate. This suggests that this osteoderm was more deeply anchored within the dermis than the other osteoderms studied hitherto. This peculiar structure might have been linked to a terrestrial ecology and a specific thermoregulation strategy. Some other notosuchians in our sample do not exhibit ornamentation on their osteoderms, as opposed to neosuchians. Considering current interpretations of osteoderm function(s) in crocodilians, our observations are discussed in reference to possible ecophysiological peculiarities of Notosuchia in general, and Iberosuchus in particular.     

Presumptive long arm deletion of chromosome 8: a new syndrome?

Summary This communication describes an infant with growth and psychomotor retardation and severe congenital malformations, who was found to have an interstitial deletion of the long arm of chromosome 8: 46,XY,del(8) (q13q22). Comparison with the only other previously reported patient with a deletion of a similar chromosomal segment suggested that deletion of the long arm of chromosome 8 may constitute a clinically recognizable syndrome.     

From where are insects recruited? A new model to interpret catches of attractive traps

Abstract 1 Two new concepts describing the origin of insects caught in an attractive trap are presented. 2 Male European pine sawflies Neodiprion sertifer Geoffroy (Hymenoptera: Diprionidae) were marked and released from 50, 100, 200, 400 and 800 m in the four cardinal directions around a centrally placed pheromone trap. 3 Based on linear regression of transformed data, we calculated the seasonal sampling range (r_s) as 1040 m. 4 We estimated the previously defined ‘effective sampling area’ (α) at 4.9 ha, assuming that the insects are evenly distributed around the trap and that they are attracted from a circular area around it. This is the area from which all insects originate if the trap is 100% effective within the area but captures nothing outside of it. The effective sampling area reveals nothing about the origin of the insects caught. We defined the Cumulative Proportional Catch (CPC) that gives the proportion of the trap catch that originates from an area within a distance r from the trap. At r = r_s CPC = 1, and in our study 50% of the captured insects originated up to 450 m from the trap. Thus, for the trap used in this study, a relatively large proportion of the catch originates some distance from the trap. 5 We also defined the Catch Concentration (CC), which is the ratio of the radius of the effective sampling area (r_α) to r_s. For our data, CC = 0.12, which is intermediate to high compared to the few other studies that we have extracted information from. If r_α is considerably lower than r_s, then only a small proportion of the insects caught originate from close proximity to the trap. When r_α is close to r_s, the catch adequately mirrors the population within most of its sampling range. 6 By using these two new concepts, we will better understand why monitoring traps mirror the local population in some cases but not in others. This will help in designing more reliable monitoring programmes.     

Hypoketotic hypofattyacidaemic hypoinsulinaemic hypoglycaemia in a child with hemihypertrophy? A new syndrome

BACKGROUND: Recurrent and persistent hypoketotic, hypofattyacidaemic hypoglycaemia in infancy and childhood is most frequently due to hyperinsulinism of infancy. This biochemical profile can also be due to non-islet cell tumour hypoglycaemia or circulating insulin-receptor autoantibodies. Hyperinsulinaemic hypoglycaemia is also seen in children with the Beckwith-Wiedemann syndrome, where it is usually transient. METHODS/RESULTS: We report a novel case of child with hemihypertrophy and severe persistent hypoketotic, hypofattyacidaemic hypoinsulinaemic hypoglycaemia. No 'big' pro-IGF2 forms or circulating insulin-receptor antibodies were found. Glucose and protein isotope turnover studies showed marked suppression of hepatic glucose production during fasting. There was no evidence for constitutive autophosphorylation of the insulin or IGF-1 receptor, and no evidence for up-regulation of IGF-1 receptor. CONCLUSION: The precise pathophysiology of this novel case is still unclear.     

A new gene for Tourette's syndrome: a window into causal mechanisms?

Gilles de la Tourette syndrome (GTS) is a neurodevelopmental disorder characterized by impairing motor-vocal tics. Locating genetic loci by associating the phenotype with DNA translocations, inversions, gain or losses, State et al. identified SLITRK1 as a candidate gene in an individual with GTS and inv(13) (q31.1; q33.1). This gene was also associated with abnormal axonal-dendritic development in embryonic mouse cells. Although SLITRK1 is not a major causal gene for GTS, it can shed light on our understanding of the gene-based neural correlates of this disease.