KBG syndrome is a neurodevelopmental autosomal dominant disorder characterized by short stature, macrodontia, developmental delay, behavioral problems, speech delay and delayed closing of fontanels. ...Most patients with KBG syndrome are found to have a mutation in the
gene or a chromosomal rearrangement involving this gene. We hereby present clinical evaluations of 23 patients aged 4 months to 26 years manifesting clinical features of KBG syndrome. Mutation analysis in the patients was performed using panel or exome sequencing and array CGH. Besides possessing dysmorphic features typical of the KBG syndrome, nearly all patients had psychomotor hyperactivity (86%), 81% had delayed speech, 61% had poor weight gain, 56% had delayed closure of fontanel and 56% had a hoarse voice. Macrodontia and a height range of -1 SDs to -2 SDs were noted in about half of the patients; only two patients presented with short stature below -3 SDs. The fact that wide, delayed closing fontanels were observed in more than half of our patients with KBG syndrome confirms the role of the
gene in skull formation and suture fusion. This clinical feature could be key to the diagnosis of KBG syndrome, especially in young children. Hoarse voice is a previously undescribed phenotype of KBG syndrome and could further reinforce clinical diagnosis.
The 3q duplication syndrome is a result of duplication of a large fragment of the long arm of chromosome 3, mainly 3q21-qter, and in most cases it is diagnosed only after birth. The phenotypic ...consequences resulting from genetic imbalance are an important source of information for genetic counselling, especially in prenatal diagnostics. However, in most cases it is impossible to define them precisely because the final clinical presentation is a result of an overlap, usually due to different sizes of deletions and/or duplications not only chromosome 3 but also of translocation partner chromosome. In this article, we present a prenatal diagnosis of the 3q duplication syndrome in a foetus, arising from a balanced insertion ins (7,3)(q21.2;q12.3q29) carried by the mother.
The article presents a case of a 29-year-old woman referred to the Genetic Outpatient Clinic for consultation in the 12th week of her fifth pregnancy with a diagnosis of generalised hydrops foetalis. The analysis of karyotype using GTG technique and FISH allowed diagnosis of a balanced aberration in the mother, and determined the type of chromosomal rearrangement, which allowed the identification of the origin of the additional genetic material in the foetus and the previous malformed child of the same couple. The use of molecular karyotyping techniques (FISH and aCGH) allowed a precise determination of the size of the imbalanced fragments in the affected siblings.
The aCGH technique is particularly valuable for the diagnostics of submicroscopic deletions and duplications, if no imbalanced chromosomal aberrations are detected by routine cytogenetic tests. It is also a valuable technique for identifying and fully characterizing genetic material of unknown origin, which can't be identified using routine cytogenetic techniqes. However, it does not allow identification of balanced aberrations in carriers.
The X and Y chromosomes are responsible for the determination and differentiation of the gonads, and their numerical and structural abnormalities may cause the abnormal development of secondary sex ...characteristics. The presence of abnormalities concerning X chromosome can also contribute to many genetically heterogeneous diseases associated with cognitive impairment and intellectual disability.
This study shows the effect of aberrations of the maternal X chromosome on the abnormal development of the child.
Ten women aged 26 to 40 years were consulted in genetic counselling clinic and subsequently subjected to cytogenetic and molecular tests due to abnormal psychomotor development of their children, in whom structural aberrations of the X chromosome had been detected.
Two women were diagnosed with changes in karyotype: 46,X,der(X)t(X;Y)(p22.3;q11.2) in one and 46,X,inv(X)(p21.2q13). Five women were diagnosed with microduplications in the short arm of the X chromosome; dupXp22.31 in one, and in four women dupXp22.33. The remaining three women were diagnosed with duplication in the long arm of the X chromosome; dupXq25 in one and dupXq26.3 in two women.
Genetic analysis of the X chromosome, based on cytogenetic and molecular methods of the highest available resolution, is extremely important in women with reproductive failure. These methods allow establishing accurately the breakpoints and rearrangements in chromosomes, and assessment of the copy number variation (CNV) can explain phenotypic variability with apparently similar aberrations. A more precise characterization of the alterations is necessary for the correct genetic diagnosis, as well as determination of the carrier status and genetic risk in family members.
The aim of this study was to determine the suitability of the comparative genomic hybridization to microarray (aCGH) technique for prenatal diagnosis, but also to assess the frequency of chromosomal ...aberrations that may lead to fetal malformations but are not included in the diagnostic report. We present the results of the aCGH in a cohort of 7400 prenatal cases, indicated for invasive testing due to ultrasound abnormalities, high-risk for serum screening, thickened nuchal translucency, family history of genetic abnormalities or congenital abnormalities, and advanced maternal age (AMA). The overall chromosomal aberration detection rate was 27.2% (2010/7400), including 71.2% (1431/2010) of numerical aberrations and 28.8% (579/2010) of structural aberrations. Additionally, the detection rate of clinically significant copy number variants (CNVs) was 6.8% (505/7400) and 0.7% (57/7400) for variants of unknown clinical significance. The detection rate of clinically significant submicroscopic CNVs was 7.9% (334/4204) for fetuses with structural anomalies, 5.4% (18/336) in AMA, 3.1% (22/713) in the group of abnormal serum screening and 6.1% (131/2147) in other indications. Using the aCGH method, it was possible to assess the frequency of pathogenic chromosomal aberrations, of likely pathogenic and of uncertain clinical significance, in the groups of cases with different indications for an invasive test.
The loss of three or more subsequent pregnancies before the end of the 22nd week is observed in 0.4-1% of women. Despite great advances in medicine, the causes of pregnancy failure (miscarriages, ...missed abortions and stillbirths), and the birth of a child or children with congenital abnormalities, are still not determined precisely
The purpose of the research was to determine the association of polymorphisms and mutations of coagulation factors II and V genes, as well as methylenetethrahydrofolate reductase (MTHFR) gene polymorphism, with the course of pregnancy and the type of reproductive failure.
The research was performed in a group of 116 women referred to the Genetic Outpatient Clinic of the NCU SM in Bydgoszcz between 2009-2010 due to reproductive failures. The molecular tests for thrombophilia, i.e. mutation of the factor V Leiden, prothrombin gene mutation 20210G>A, and MTHFR polymorphism 677C>T were done in all patients.
The Leiden mutation was found in 8 women (homozygotic in 2 of them) and prothrombin gene mutation in 3.85 women had the heterozygotic MTHFR polymorphism, while 24 the homozygotic one. Coexistence of the Leiden mutation and the MTHFR polymorphism was found in 3 patients with history of miscarriages.
1. The presence of the mutations that promote thrombophilia in the genes responsible for the foliate metabolism and for the plasma coagulation is often associated with pregnancy failures and may be their basic cause in some cases. 2. The percentage of women with pregnancy failures being heterozygotes (73.3%), homozygotes (20.7%) or both (94%) of the MTHFR gene 677C>T polymorphism is statistically significantly higher than the highest prevalence of these changes in the general population (55, 13%, and 68%, respectively). 3. The factor V gene Leiden mutation is associated mainly with recurrent spontaneous abortions. In the present study it was found only in the group of women with both early and late miscarriages.
IntroductionThe X and Y chromosomes are responsible for the determination and differentiation of the gonads, and their numerical and structural abnormalities may cause the abnormal development of ...secondary sex characteristics. The presence of abnormalities concerning X chromosome can also contribute to many genetically heterogeneous diseases associated with cognitive impairment and intellectual disability. PurposeThis study shows the effect of aberrations of the maternal X chromosome on the abnormal development of the child. Patients and MethodsTen women aged 26 to 40 years were consulted in genetic counselling clinic and subsequently subjected to cytogenetic and molecular tests due to abnormal psychomotor development of their children, in whom structural aberrations of the X chromosome had been detected. ResultsTwo women were diagnosed with changes in karyotype: 46,X,der(X)t(X;Y)(p22.3;q11.2) in one and 46,X,inv(X)(p21.2q13). Five women were diagnosed with microduplications in the short arm of the X chromosome; dupXp22.31 in one, and in four women dupXp22.33. The remaining three women were diagnosed with duplication in the long arm of the X chromosome; dupXq25 in one and dupXq26.3 in two women. ConclusionGenetic analysis of the X chromosome, based on cytogenetic and molecular methods of the highest available resolution, is extremely important in women with reproductive failure. These methods allow establishing accurately the breakpoints and rearrangements in chromosomes, and assessment of the copy number variation (CNV) can explain phenotypic variability with apparently similar aberrations. A more precise characterization of the alterations is necessary for the correct genetic diagnosis, as well as determination of the carrier status and genetic risk in family members.
Swi2/Snf2 ATPases remodel substrates such as nucleosomes and transcription complexes to control a wide range of DNA-associated processes, but detailed structural information on the ATP-dependent ...remodeling reactions is largely absent. The single subunit remodeler Mot1 (modifier of transcription 1) dissociates TATA box-binding protein (TBP):DNA complexes, offering a useful system to address the structural mechanisms of Swi2/Snf2 ATPases. Here, we report the crystal structure of the N-terminal domain of Mot1 in complex with TBP, DNA, and the transcription regulator negative cofactor 2 (NC2). Our data show that Mot1 reduces DNA:NC2 interactions and unbends DNA as compared to the TBP:DNA:NC2 state, suggesting that Mot1 primes TBP:NC2 displacement in an ATP-independent manner. Electron microscopy and cross-linking data suggest that the Swi2/Snf2 domain of Mot1 associates with the upstream DNA and the histone fold of NC2, thereby revealing parallels to some nucleosome remodelers. This study provides a structural framework for how a Swi2/Snf2 ATPase interacts with its substrate DNA:protein complex.
During the COVID-19 pandemic, many people were anxious about a coronavirus infection due to the high infection rate and the mortality risk associated with the disease. Fear of COVID-19 might have ...influenced patients’ utilisation of medical services, even if it meant that a postponed therapy had severe consequences. Our aims were to analyse (a) to what extent fear of COVID-19 contributes to forgone consultations, (b) if patient characteristics, health literacy and social support influence the effect of fear of COVID-19 on the utilisation behaviour and (c) whether interactions between these possible predictor variables are responsible for a higher extent of avoided consultations due to fear of COVID-19.
We conducted a retrospective, cross-sectional observational study in an emergency department. The study was based on personal standardized interviews of patients. The interviews took place between July 15 and August 5, 2020. Patients over the age of 18 were included if there was no urgent need for treatment on the day of the interview, no severe functional limitations, sufficient knowledge of German, ability to consent and health problems requiring treatment between March 13 and June 13, 2020. Differences between patient subgroups were described and analysed using the t-test and chi2 test. Data were analysed by logistic regression including socio-demographic data, health literacy and social support assessed by standardised instruments. Additionally, we assessed interactions between possible predictor variables by a descriptive tree analysis.
103 patients participated in personal standardized interviews. 46 patients (44.6%) reported that at least one necessary consultation did not take place in the observation period. Among those, 29 patients (63.0%) avoided consultations due to fear of COVID-19. Women had 3.36 times higher odds (95% confidence interval: 1.25 to 9.04, p = 0.017) for avoiding a consultation due to fear of COVID-19. There were no other statistically significant predictors in our analysis.
Almost half of the required consultations did not take place. Avoidance of consultations needs to be closely monitored during the pandemic. Policy makers as well as health care providers should give consideration to the collateral effects of COVID-19 and COVID-19-related reactions of patients, especially women.
In the course of the COVID-19 pandemic, physicians should ensure that their patients take advantage of necessary consultations in order to avoid negative effects of a delayed examination or treatment. Particular attention should be paid to anxious female patients. Studies are needed to analyse the association between health literacy, social support and avoidance of consultations triggered by fear of COVID-19.
Aufgrund rasch steigender Infektionszahlen zu Beginn der COVID-19-Pandemie und des mit dieser Krankheit verbundenen Mortalitätsrisikos hatten viele Menschen Angst vor einer COVID-19-Infektion. Diese Angst könnte die Inanspruchnahme medizinischer Versorgungsleistungen negativ beeinflusst haben, sogar hinsichtlich notwendiger Konsultationen. Unsere Ziele waren es zu analysieren, (a) inwieweit die Angst vor COVID-19 zum Verzicht auf Konsultationen beiträgt, (b) ob Patientencharakteristika, Gesundheitskompetenz und soziale Unterstützung den Einfluss der Angst vor COVID-19 auf das Inanspruchnahmeverhalten beeinflussen und (c) ob Wechselwirkungen zwischen diesen möglichen Prädiktorvariablen für ein höheres Ausmaß vermiedener Konsultationen aufgrund von Angst vor COVID-19 verantwortlich sind.
Es wurde eine retrospektive, querschnittliche Beobachtungsstudie basierend auf persönlichen standardisierten Interviews mit Patient:innen in einer Zentralen Notaufnahme durchgeführt. Die Interviews fanden in dem Zeitraum 15. Juli bis 5. August 2020 statt. Über 18-Jährige Patient:innen wurden eingeschlossen, wenn keine dringende Behandlungsbedürftigkeit am Tag des Interviews, keine schweren Funktionseinschränkungen, ausreichende Deutschkenntnisse, Einwilligungsfähigkeit und behandlungsbedürftige gesundheitliche Probleme zwischen dem 13. März und 13. Juni 2020 vorlagen. Unterschiede zwischen Patient:innengruppen wurden beschrieben und mithilfe des t-Tests und des Chi2-Tests analysiert. Die Daten wurden durch logistische Regression analysiert, einschließlich soziodemografischer Daten, Gesundheitskompetenz und sozialer Unterstützung, die durch standardisierte Instrumente erhoben wurden. Zusätzlich wurden Wechselwirkungen zwischen möglichen Prädiktorvariablen durch eine deskriptive Baumanalyse bewertet.
103 Patient:innen nahmen an den persönlichen standardisierten Interviews teil. 46 Patient:innen (44,6%) gaben an, dass mindestens eine notwendige Konsultation im Beobachtungszeitraum nicht stattfinden konnte. Davon vermieden 29 Patient:innen (63,0 %) die Konsultationen aus Angst vor COVID-19. Frauen hatten eine 3,36-mal höhere Wahrscheinlichkeit (95%-KI: 1,25 bis 9,04, p = 0,017), eine Konsultation aus Angst vor COVID-19 zu vermeiden. Es gab keine anderen statistisch signifikanten Prädiktoren in unserer Analyse.
Fast die Hälfte der erforderlichen Konsultationen konnte nicht stattfinden. Die Vermeidung von Konsultationen muss während einer Pandemie im Auge behalten werden. Politische Entscheidungsträger:innen und Beschäftigte im Gesundheitswesen sollten die Auswirkungen von COVID-19 und COVID-19-bedingte Reaktionen von Patient:innen, insbesondere von Frauen, berücksichtigen.
Ärzt:innen sollten im Zuge der COVID-19-Pandemie besonders darauf achten, dass ihre Patient:innen notwendige Konsultationen in Anspruch nehmen, um negative Auswirkungen einer verspäteten Untersuchung oder Behandlung zu vermeiden. Ein besonderes Augenmerk gilt ängstlichen Patient:innen. Es sind Studien erforderlich, die den Zusammenhang zwischen Gesundheitskompetenz, sozialer Unterstützung und der Angst vor einer durch COVID-19 ausgelösten Vermeidung von Konsultationen analysieren.
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