Reading projects

"By reading only six hours a day", says Marianne Dashwood, outlining her plan of future application to her sister Elinor in Sense and Sensibility, "I shall gain in the course of a twelve-month a great deal of instruction which I now feel myself to want." She adds: "Our own library is too well known to me, to be resorted to for any thing beyond mere amusement. But there are many works well worth reading at the Park; and there are others of more modern production which I know I can borrow of Colonel Brandon" (301). We know, to some extent, what was in the Dashwoods' own library – volumes of Cowper, Scott and Thomson are mentioned. But what might Marianne have borrowed at Barton Park and Delaford? Which publications would Colonel Brandon have considered most appropriate for her project of self-improvement? Elinor considers Marianne's plan excessive, but what would have been a more realistic amount of time for her to spend reading each day, and where might she have done it

Genome-wide DNA methylation analysis of pseudohypoparathyroidism patients with GNAS imprinting defects

Background: Pseudohypoparathyroidism (PHP) is caused by (epi) genetic defects in the imprinted GNAS cluster. Current classification of PHP patients is hampered by clinical and molecular diagnostic overlaps. The European Consortium for the study of PHP designed a genome-wide methylation study to improve molecular diagnosis. Methods: The Human Methylation 450K BeadChip was used to analyze genome-wide methylation in 24 PHP patients with parathyroid hormone resistance and 20 age- and gender-matched controls. Patients were previously diagnosed with GNAS-specific differentially methylated regions (DMRs) and include 6 patients with known STX16 deletion (PHP Delta stx16) and 18 without deletion (PHPneg). Results: The array demonstrated that PHP patients do not show DNA methylation differences at the whole-genome level. Unsupervised clustering of GNAS-specific DMRs divides PHP Delta stx16 versus PHPneg patients. Interestingly, in contrast to the notion that all PHP patients share methylation defects in the A/B DMR while only PHP Delta stx16 patients have normal NESP, GNAS-AS1 and XL methylation, we found a novel DMR (named GNAS-AS2) in the GNAS-AS1 region that is significantly different in both PHP Delta stx16 and PHPneg, as validated by Sequenom EpiTYPER in a larger PHP cohort. The analysis of 58 DMRs revealed that 8/18 PHPneg and 1/6 PHP Delta stx16 patients have multi-locus methylation defects. Validation was performed for FANCC and SVOPL DMRs. Conclusions: This is the first genome-wide methylation study for PHP patients that confirmed that GNAS is the most significant DMR, and the presence of STX16 deletion divides PHP patients in two groups. Moreover, a novel GNAS-AS2 DMR affects all PHP patients, and PHP patients seem sensitive to multi-locus methylation defects

Growth response of syndromic versus non-syndromic children born small for gestational age (SGA) to growth hormone therapy: a Belgian study

IntroductionA substantial proportion of SGA patients present with a syndrome underlying their growth restriction. Most SGA cohorts comprise both syndromic and non-syndromic patients impeding delineation of the recombinant human growth hormone (rhGH) response. We present a detailed characterization of a SGA cohort and analyze rhGH response based on adult height (AH).MethodsClinical and auxological data of SGA patients treated with rhGH, who had reached AH, were retrieved from BELGROW, a national database of all rhGH treated patients held by BESPEED (BElgian Society for PEdiatric Endocrinology and Diabetology). SGA patients were categorized in syndromic or non-syndromic patients.Results272 patients were included, 42 classified as syndromic (most frequent diagnosis (n=6): fetal alcohol syndrome and Silver-Russell syndrome). Compared with non-syndromic patients, syndromic were younger [years (median (P10/P90)] 7.43 (4.3/12.37) vs 10.21 (5.43/14.03), p=0.0005), shorter (height SDS -3.39 (-5.6/-2.62) vs -3.07 (-3.74/-2.62), p=0.0253) and thinner (BMI -1.70 (-3.67/0.04) vs -1.14 (-2.47/0.27) SDS, p=0.0054) at start of rhGH treatment. First year rhGH response was comparable (delta height SDS +0.54 (0.24/0.94) vs +0.56 (0.26/0.92), p=0.94). Growth pattern differed with syndromic patients having a higher prepubertal (SDS +1.26 vs +0.83, p=0.0048), but a lower pubertal height gain compared to the non-syndromic group (SDS -0.28 vs 0.44, p=0.0001). Mean rhGH dose was higher in syndromic SGA patients (mg/kg body weight/day 0.047 (0.039/0.064) vs 0.043 (0.035/0.056), p=0.0042). AH SDS was lower in syndromic SGA patients (-2.59 (-4.99/-1.57) vs -2.32 (-3.3/-1.2), p=0.0107). The majority in both groups remained short (<-2 SDS: syndromic 71%, non-syndromic 63%). Total height gain was comparable in both groups (delta height SDS +0.76 (-0.70/1.48) vs +0.86 (-0.12/1.86), p=0.41).ConclusionsCompared to non-syndromic SGA patients, syndromic SGA patients were shorter when starting rhGH therapy, started rhGH therapy earlier, and received a higher dose of rhGH. At AH, syndromic SGA patients were shorter than non-syndromic ones, but their height gain under rhGH therapy was comparable

Een 14-jarige jongen met thoracale pijn

status: publishe

Hypothalamic lipoma and growth hormone deficiency

Background: Intracranial lipomas are rare, congenital lesions, most often located at the midline. Most hypothalamic lipomas are asymptomatic, but some cases have been associated with precocious puberty, hypothermia, headache and/or obesity. Case presentation: A 7-year-old boy was referred for short stature and proved to be partially growth-hormone deficient. Magnetic resonance imaging (MRI) revealed a lipoma in the paramedian hypothalamus. Growth hormone treatment resulted in swift and uncomplicated catch-up growth. Conclusions: The present case appears to be the first to link hypothalamic lipoma to GH deficiency. The neuro-endocrine pathophysiology underpinning this link remains to be explored.status: publishe

Made in Belgium: DNA methylation studies in Spina Bifida

status: Published onlin

Acute mastoiditis

no ISSNstatus: publishe

Nutri-epigenomic Studies Related to Neural Tube Defects: Does Folate Affect Neural Tube Closure Via Changes in DNA Methylation?

Neural tube defects (NTDs), affecting 1-2 per 1000 pregnancies, are severe congenital malformations that arise from the failure of neurulation during early embryonic development. The methylation hypothesis suggests that folate prevents NTDs by stimulating cellular methylation reactions. Folate is central to the one-carbon metabolism that produces pyrimidines and purines for DNA synthesis and for the generation of the methyldonor S-adenosyl-methionine. This review focuses on the relation between the folate-mediated one-carbon metabolism, DNA methylation and NTDs. Studies will be discussed that investigated global or locus-specific DNA methylation differences in patients with NTDs. Folate deficiency may increase NTD risk by decreasing DNA methylation, but to date, human studies vary widely in study design in terms of analyzing different clinical subtypes of NTDs, using different methylation quantification assays and using DNA isolated from diverse types of tissues. Some studies have focused mainly on global DNA methylation differences while others have quantified specific methylation differences for imprinted genes, transposable elements and DNA repair enzymes. Findings of global DNA hypomethylation and LINE-1 hypomethylation suggest that epigenetic alterations may disrupt neural tube closure. However, current research does not support a linear relation between red blood cell folate concentration and DNA methylation. Further studies are required to better understand the interaction between folate, DNA methylation changes and NTDs.status: publishe

The future Paediatricians in Flanders.

status: Published onlin