MAB21L1 loss of function causes a syndromic neurodevelopmental disorder with distinctive cerebellar, ocular, craniofacial and genital features (COFG syndrome).

BACKGROUND: Putative nucleotidyltransferase MAB21L1 is a member of an evolutionarily well-conserved family of the male abnormal 21 (MAB21)-like proteins. Little is known about the biochemical function of the protein; however, prior studies have shown essential roles for several aspects of embryonic development including the eye, midbrain, neural tube and reproductive organs. OBJECTIVE: A homozygous truncating variant in MAB21L1 has recently been described in a male affected by intellectual disability, scrotal agenesis, ophthalmological anomalies, cerebellar hypoplasia and facial dysmorphism. We employed a combination of exome sequencing and homozygosity mapping to identify the underlying genetic cause in subjects with similar phenotypic features descending from five unrelated consanguineous families. RESULTS: We identified four homozygous MAB21L1 loss of function variants (p.Glu281fs*20, p.Arg287Glufs*14 p.Tyr280* and p.Ser93Serfs*48) and one missense variant (p.Gln233Pro) in 10 affected individuals from 5 consanguineous families with a distinctive autosomal recessive neurodevelopmental syndrome. Cardinal features of this syndrome include a characteristic facial gestalt, corneal dystrophy, hairy nipples, underdeveloped labioscrotal folds and scrotum/scrotal agenesis as well as cerebellar hypoplasia with ataxia and variable microcephaly. CONCLUSION: This report defines an ultrarare but clinically recognisable Cerebello-Oculo-Facio-Genital syndrome associated with recessive MAB21L1 variants. Additionally, our findings further support the critical role of MAB21L1 in cerebellum, lens, genitalia and as craniofacial morphogenesis

Authoritarian Neoliberalism and Democratic Backsliding in Turkey: Beyond the Narratives of Progress

Unpacking the core themes that are discussed in this collection, this article both offers a research agenda to re-analyse Turkey’s ‘authoritarian turn’ and mounts a methodological challenge to the conceptual frameworks that reinforce a strict analytical separation between the ‘economic’ and the ‘political’ factors. The paper problematises the temporal break in scholarly analyses of the AKP period and rejects the argument that the party’s methods of governance have shifted from an earlier ‘democratic’ model – defined by ‘hegemony’ – to an emergent ‘authoritarian’ one. In contrast, by retracing the mechanisms of the state-led reproduction of neoliberalism since 2003, the paper demonstrates that the party’s earlier ‘hegemonic’ activities were also shaped by authoritarian tendencies which manifested at various levels of governance

Lunapark deficiency leads to an autosomal recessive neurodevelopmental phenotype with a degenerative course, epilepsy and distinct brain anomalies.

LNPK encodes a conserved membrane protein that stabilizes the junctions of the tubular endoplasmic reticulum network playing crucial roles in diverse biological functions. Recently, homozygous variants in LNPK were shown to cause a neurodevelopmental disorder (OMIM#618090) in four patients displaying developmental delay, epilepsy and nonspecific brain malformations including corpus callosum hypoplasia and variable impairment of cerebellum. We sought to delineate the molecular and phenotypic spectrum of LNPK-related disorder. Exome or genome sequencing was carried out in 11 families. Thorough clinical and neuroradiological evaluation was performed for all the affected individuals, including review of previously reported patients. We identified 12 distinct homozygous loss-of-function variants in 16 individuals presenting with moderate to profound developmental delay, cognitive impairment, regression, refractory epilepsy and a recognizable neuroimaging pattern consisting of corpus callosum hypoplasia and signal alterations of the forceps minor ('ear-of-the-lynx' sign), variably associated with substantia nigra signal alterations, mild brain atrophy, short midbrain and cerebellar hypoplasia/atrophy. In summary, we define the core phenotype of LNPK-related disorder and expand the list of neurological disorders presenting with the 'ear-of-the-lynx' sign suggesting a possible common underlying mechanism related to endoplasmic reticulum-phagy dysfunction

Biallelic MED27 variants lead to variable ponto-cerebello-lental degeneration with movement disorders.

MED27 is a subunit of the Mediator multiprotein complex, which is involved in transcriptional regulation. Biallelic MED27 variants have recently been suggested to be responsible for an autosomal recessive neurodevelopmental disorder with spasticity, cataracts and cerebellar hypoplasia. We further delineate the clinical phenotype of MED27-related disease by characterizing the clinical and radiological features of 57 affected individuals from 30 unrelated families with biallelic MED27 variants. Using exome sequencing and extensive international genetic data sharing, 39 unpublished affected individuals from 18 independent families with biallelic missense variants in MED27 have been identified (29 females, mean age at last follow-up 17 ± 12.4 years, range 0.1-45). Follow-up and hitherto unreported clinical features were obtained from the published 12 families. Brain MRI scans from 34 cases were reviewed. MED27-related disease manifests as a broad phenotypic continuum ranging from developmental and epileptic-dyskinetic encephalopathy to variable neurodevelopmental disorder with movement abnormalities. It is characterized by mild to profound global developmental delay/intellectual disability (100%), bilateral cataracts (89%), infantile hypotonia (74%), microcephaly (62%), gait ataxia (63%), dystonia (61%), variably combined with epilepsy (50%), limb spasticity (51%), facial dysmorphism (38%) and death before reaching adulthood (16%). Brain MRI revealed cerebellar atrophy (100%), white matter volume loss (76.4%), pontine hypoplasia (47.2%) and basal ganglia atrophy with signal alterations (44.4%). Previously unreported 39 affected individuals had seven homozygous pathogenic missense MED27 variants, five of which were recurrent. An emerging genotype-phenotype correlation was observed. This study provides a comprehensive clinical-radiological description of MED27-related disease, establishes genotype-phenotype and clinical-radiological correlations and suggests a differential diagnosis with syndromes of cerebello-lental neurodegeneration and other subtypes of 'neuro-MEDopathies'

Social support and hopelessness in patients with breast cancer

Background: Patients with breast cancer can experience a feeling of hopelessness very deeply in the adjustment process, and the social support provided during this period can be effective in increasing the level of hope. The present study aimed to identify breast cancer patients' social support and hopelessness level. Materials and Methods: The target population of this analytical study was all breast cancer patients (total of 85) who had treatment in the oncology department of a university hospital located in Adana/Turkey and who met the inclusion criteria. Data were collected through "Personal Information Form", "Beck Hopelessness Scale (BHS)" and "Multidimensional Scale of Perceived Social Support" (MSPSS). Analysis was performed using Shapiro Wilk, One Way ANOVA Welch, Student t-test, Mann Whitney U, and Kruskall Wallis tests. Homogeneity of variance was tested with the Levene, Bonferroni and Games Howell tests. Mean scores and standard deviation values are given as descriptive statistics. Results: Average age of the participants with breast cancer is 48.6±10.6. Of all the participants, 84.7% are married, 49.4% graduated from primary school, 81.2% are housewives, and 82.4% had children. The participants' multidimensional perceived social support total scores were found to be high (57.41±13.97) and hopelessness scale scores low (5.49±3.80). There was a reverse, linear relationship between hopelessness scale scores and social support total scores (r=-0.259, p=0.017). A statistically significant relationship was found between hopelessness scores and education level and having children, occupation, income status, and education level of spouses (p<0.05). Conclusions: The present study indicates that hopelessness of the patients with breast cancer decreased with the increase in their social support. Therefore, activating patient social support systems is of importance in increasing their level of hope

Evolution of Modern Forest Management Planning in the Republic of Turkey

Bettinger, Pete/0000-0002-5454-3970; Yesil, Ahmet/0000-0002-2494-0326WOS: 000322933000001The Republic of Turkey has a long history of forest management that has undergone considerable change over the last 100 years due to political, economic, and social issues. For the most part, state-owned forestlands (the largest forest owner category) have been managed under plans arising from a conventional process that used classic techniques to regulate activities and allowable harvest levels. However, over the last 35 years, four different types of forest management plans have been developed (conventional and model) and applied universally or to a specific region of the country. Today, a single type of planning process is used, which emphasizes ecological and environmental conditions, multiple uses of the landscape, and social concerns. Although management and planning are evolving, implementation is challenged by a continued focus on wood production rather than on other concerns, a lack of skilled personnel and qualified decisionmakers, and other societal conflicts.Istanbul UniversityIstanbul University; Duzce UniversityDuzce University; Higher Education Council of Turkey (YOK)Ministry of National Education - TurkeyWe appreciate the financial assistance of Istanbul University, Duzce University, and the Higher Education Council of Turkey (YOK)

Correlation Between Cytological And Histopathological Diagnosis In Premalignant Lesions Of The Cervix

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