4 research outputs found
Epigenotype-genotype-phenotype correlations in SETD1A and SETD2 chromatin disorders
Germline pathogenic variants in two genes encoding the lysine-specific histone methyltransferase genes SETD1A and SETD2 are associated with neurodevelopmental disorders (NDDs) characterised by developmental delay and congenital anomalies. The SETD1A and SETD2 gene products play a critical role in chromatin-mediated regulation of gene expression. Specific methylation episignatures have been detected for a range of chromatin gene-related NDDs and have impacted clinical practice by improving interpretation of variant pathogenicity. To investigate if SETD1A and/or SETD2-related NDDs are associated with a detectable episignature, we undertook targeted genome-wide methylation profiling of > 2 M CpGs using a next generation sequencing based assay. Comparison of methylation profiles in patients with SETD1A variants (n = 6) did not reveal evidence of a strong methylation episignature. Review of the clinical and genetic features of SETD2 patient group revealed that, as reported previously, there were phenotypic differences between patients with truncating mutations (n = 4, Luscan-Lumish syndrome; MIM:616831) and those with missense codon 1740 variants (p.Arg1740Trp (n = 4) and p.Arg1740Gln (n = 2)). Both SETD2 subgroups demonstrated a methylation episignature which was characterised by hypomethylation and hypermethylation events respectively. Within the codon 1740 subgroup, both the methylation changes and clinical phenotype were more severe in those with p.Arg1740Trp variants. We also noted that two of 10 cases with a SETD2-NDD had developed a neoplasm. These findings reveal novel epigenotype-genotype–phenotype correlations in SETD2-NDDs and predict a gain-of-function mechanism for SETD2 codon 1740 pathogenic variants
Biological and psychosocial sex and gender differences in patients with epilepsy
EINLEITUNG: In vielen Bereichen der Medizin zeigt sich wachsende Evidenz fĂĽr
relevante Geschlechterunterschiede, Beispiele sind kardiologische und
immunologische Erkrankungen oder die weltweit um ca. 10 Jahre niedrigere
Lebenserwartung von Männern. Zu Geschlechterunterschieden im Bereich der
Epilepsien gibt es bislang kaum Erkenntnisse. Ziel dieser Arbeit ist es daher,
in einem explorativen Ansatz Unterschiede in den Bereichen der
Epilepsiesyndrome, Pharmakotherapie, Anfallskontrolle und psychosozialen
Variablen zu untersuchen. METHODIK: Im Rahmen einer monozentrischen
Querschnittsstudie wurden Patienten der Epilepsie-Hochschulambulanzen der
Charité mittels eines semistrukturierten Interviews befragt, welches neben
Angaben zu Medikation und Soziodemographie auch standardisierte Fragebögen zur
Erfassung von Depressionen (PHQ-D), Angststörungen (HADS-A), sozialer
Unterstützung (ESSI, MuSK) und gesundheitsspezifischer Lebensqualität
(QOLIE-31-P) umfasste. Epilepsiespezifische Variablen wurden mithilfe der
Patientenakten verifiziert und vervollständigt. Bei allen Patienten wurde
routinemäßig die Serumkonzentration der Antiepileptika bestimmt. ERGEBNISSE:
Ausgewertet wurden Datensätze von 302 Patienten (53,3% weiblich). IGEs lagen
signifikant häufiger bei Frauen vor (34,2% der Frauen, 11,3% der Männer,
p<0,001), fokale Epilepsien häufiger bei Männern (58,4% der Frauen, 85,1% der
Männer, p<0,001). Entsprechend der Epilepsiesyndrome verteilten sich die
Anfallstypen, unabhängig davon wurden EFA signifikant häufiger von Frauen mit
fokaler Epilepsie berichtet (p=0,12). Patienten mit IGE waren signifikant
häufiger anfallsfrei als Patienten mit fokaler Epilepsie (p<0,001). Weibliches
Geschlecht war ein unabhängiger negativer Prädiktor für Anfallsfreiheit in den
letzten 3 Monaten (p=0,030, Exp(B) 0,528). Männer wurden häufiger mit
antiepileptischer Polytherapie behandelt (p=0,014). Keine
Geschlechterunterschiede zeigten sich bei der Wahl der Substanzen oder den
Dosierungen der AED, ebenso wenig wurden signifikante Unterschiede der
Serumkonzentrationen nachgewiesen. Nebenwirkungen der antiepileptischen
Therapie waren häufig (40,1%) und unterschieden sich zwischen den
Geschlechtern: Müdigkeit, Sehstörungen, Hautprobleme und Gewichtszunahme
wurden häufiger von Frauen genannt, Gang- und Gleichgewichtsstörungen
vornehmlich von Männern. Das Depressionsscreening (PHQ-D) zeigte eine höhere
Symptombelastung der Frauen, wobei fĂĽr Major Depression suggestive Werte bei
beiden Geschlechtern gleich häufig vorlagen (insgesamt 11,3%). Auch
Angstsymptomatik (HADS-A) war zwischen Männern und Frauen gleich verteilt
(grenzwertige/ krankheitswertige HADS-A-Scores bei insgesamt 67,3%). Die
subjektiv wahrgenommene soziale Unterstützung (ESSI) war bei Männern
signifikant niedriger als bei Frauen (p=0,039), insgesamt jedoch hoch.
Umgekehrt zeigte sich die gesundheitsbezogene Lebensqualität (QOLIE-31-P) bei
den Frauen geringer (p=0,008). SCHLUSSFOLGERUNG: In vielen klinisch relevanten
Bereichen konnten signifikante Unterschiede zwischen Männern und Frauen mit
Epilepsie gezeigt werden, in anderen Bereichen (wie den affektiven Störungen)
zeigten sich die beiden Gruppen ĂĽberraschend homogen. Diese Arbeit zu
Geschlechterunterschieden bei Epilepsien liefert Ansätze für Interventionen im
klinischen Alltag und zeigt zudem den Bedarf fĂĽr weiterreichende Forschung
auf.INTRODUCTION: Mounting evidence exists for relevant sex differences in various
medical fields. Examples are cardiologic or immune-mediated diseases as well
as general life expectancy, which is 10 years lower for men worldwide.
Nevertheless, little is known about sex differences in epilepsies. This study
explores sex/gender differences in epilepsy syndromes, pharmacotherapy,
response to treatment and psychosocial variables. METHODS: By means of a
monocentric cross-sectional study, adult epilepsy outpatients at Charité
University Hospital completed a semi-structured interview containing
information about AED, response to treatment, sociodemographic situation and
standardized questionnaires for depression (PHQ-D), anxiety disorders
(HADS-A), social support (ESSI, MuSK) and health-related quality of life
(QOLIE-31-P). Epilepsy-related information were verified and completed with
patient records. Serum concentration of AED was routinely measured in all
patients. RESULTS: Data of 302 patients (53.3% female) were evaluated.
Idiopathic generalized epilepsies were significantly more frequent in women
(34.2% of all women, 11.3% of all men, p<0.001), while partial epilepsies
predominated in men (58.4% of all women, 85.1% of all men, p<0.001). Seizure
types were distributed according to epilepsy syndromes, however, in focal
epilepsies simple partial seizures were more frequently reported by women
(p=0.012). Seizure freedom occurred significantly more often in patients with
IGE than in those with partial epilepsies (p<0.001). Female sex was an
independent negative predictor for seizure freedom in the preceding 3 months
(p=0.030, Exp(B) 0.528). Men were treated more often with antiepileptic
polytherapy (p=0.014). Sex differences were found neither in choice of
substance nor in AED dosages, also in serum concentrations no significant
differences were proven. Adverse effects of antiepileptic therapy were
frequent (40.1%) and differed between the sexes: women frequently reported
tiredness, visual impairment, skin irritation and weight gain, while
disturbances of gait/balance predominantly affected men. Screening for
depressive symptoms (PHQ-D) showed higher scores in women, while suggestive
scores for major depression equalled in both sexes (total 11.3%). There was no
sex/gender difference in anxiety scores (borderline/pathologic HADS-A-scores
in 67.3%). Subjectively perceived social support (ESSI) was significantly
lower in men (p=0.039), while generally high. Conversely, health-related
quality of life (QOLIE-31-P) was lower in women (p=0.008). CONCLUSION:
Differences between men and women with epilepsy could be shown in various
clinically relevant areas, while in other domains (i.e. affective disorders)
both groups seemed surprisingly homogeneous. This study on sex and gender
differences in epilepsies gives impulses for interventions in clinical routine
and points out the urgent need for further research
The Impact of Demographic Characteristics on Parenting Stress among Parents of Children with Disabilities: A Cross-Sectional Study
Even though it is already known that parents of children with developmental delays or disabilities experience higher parenting stress than families of typically developing children, the contributing factors need to be analyzed in more detail. The aim of this cross-sectional study was to examine the influence of demographic characteristics on parenting stress from caring for a disabled child and to identify possible protective or additional stressful social factors. A total of 611 mothers and fathers of children with developmental delays, chronic diseases, or disabilities completed two questionnaires during their medical appointments at the Children’s Development Center (CDC) of Leipzig University Hospital between June 2020 and February 2021. These consisted of the German versions of the Parenting Stress Index (PSI) and the Impact on Family Scale (IOFS). To determine differences between the various groups, we used parametric and non-parametric tests. Mothers and single parents are significantly more strained than fathers and non-single parents. Parents with vocational training, those who graduated with a higher-level diploma, and those within employment report a higher financial burden. While unemployed and full-time workers experience the lowest stress, parents who work part-time or exclusively take care of their child show higher levels of stress. Looking at the age of the child, parents of children of young primary school age are the most stressed, and those of infants are the least stressed. These findings suggest that mothers and single parents especially should receive more support, and parents need to be provided with more attention during their child’s entry into school. Possible limitations and the influence of the COVID-19 pandemic are discussed