Objective FOXG1 syndrome is a rare neurodevelopmental disorder associated with heterozygous FOXG1 variants or chromosomal microaberrations in 14q12. The study aimed at assessing the scope of structural cerebral anomalies revealed by neuroimaging to delineate the genotype and neuroimaging phenotype associations. Methods We compiled 34 patients with a heterozygous (likely) pathogenic FOXG1 variant. Qualitative assessment of cerebral anomalies was performed by standardized re-analysis of all 34 MRI data sets. Statistical analysis of genetic, clinical and neuroimaging data were performed. We quantified clinical and neuroimaging phenotypes using severity scores. Telencephalic phenotypes of adult Foxg1+/− mice were examined using immunohistological stainings followed by quantitative evaluation of structural anomalies. Results Characteristic neuroimaging features included corpus callosum anomalies (82%), thickening of the fornix (74%), simplified gyral pattern (56%), enlargement of inner CSF spaces (44%), hypoplasia of basal ganglia (38%), and hypoplasia of frontal lobes (29%). We observed a marked, filiform thinning of the rostrum as recurrent highly typical pattern of corpus callosum anomaly in combination with distinct thickening of the fornix as a characteristic feature. Thickening of the fornices was not reported previously in FOXG1 syndrome. Simplified gyral pattern occurred significantly more frequently in patients with early truncating variants. Higher clinical severity scores were significantly associated with higher neuroimaging severity scores. Modeling of Foxg1 heterozygosity in mouse brain recapitulated the associated abnormal cerebral morphology phenotypes, including the striking enlargement of the fornix. Interpretation Combination of specific corpus callosum anomalies with simplified gyral pattern and hyperplasia of the fornices is highly characteristic for FOXG1 syndrome.
Annals of Clinical and Translational Neurology Chichester [u.a.] : Wiley, 2013 6(2019), 4, Seite 655-668 Online-Ressource
von Sven Dittrich ; Joseph George Pattathu ; Friedrich Ebinger ; Joachim Eichhorn ; Reinald Motz ; Christoph Korenke ; Matthias Freund ; Michael Schumacher
X-linked Duchenne muscular dystrophy (DMD), the most frequent human hereditary skeletal muscle myopathy, inevitably leads to progressive dilated cardiomyopathy. We assessed the effect and safety of a combined treatment with the ACE-inhibitor enalapril and the β-blocker metoprolol in a German cohort of infantile and juvenile DMD patients with preserved left ventricular function.
Orphanet journal of rare diseases London : BioMed Central, 2006 14(2019), Artikel-ID 105, Seite 1-13 Online-Ressource
Gesehen am 24.04.2020 ; Advance online publication: 29 June 2017
Child; Child, Preschool; DNA Mutational Analysis; Female; Forkhead Transcription Factors; Genetic Association Studies; Genetic Variation; Genotype; Humans; Magnetic Resonance Imaging; Male; Nerve Tissue Proteins; Phenotype; Polymorphism, Single Nucleotide; Rett Syndrome
Purpose: The study aimed at widening the clinical and genetic spectrum and assessing genotype-phenotype associations in FOXG1 syndrome due to FOXG1 variants. Methods: We compiled 30 new and 53 reported patients with a heterozygous pathogenic or likely pathogenic variant in FOXG1. We grouped patients according to type and location of the variant. Statistical analysis of molecular and clinical data was performed using Fisher's exact test and a nonparametric multivariate test. Results: Among the 30 new patients, we identified 19 novel FOXG1 variants. Among the total group of 83 patients, there were 54 variants: 20 frameshift (37%), 17 missense (31%), 15 nonsense (28%), and 2 in-frame variants (4%). Frameshift and nonsense variants are distributed over all FOXG1 protein domains; missense variants cluster within the conserved forkhead domain. We found a higher phenotypic variability than previously described. Genotype-phenotype association revealed significant differences in psychomotor development and neurological features between FOXG1 genotype groups. More severe phenotypes were associated with truncating FOXG1 variants in the N-terminal domain and the forkhead domain (except conserved site 1) and milder phenotypes with missense variants in the forkhead conserved site 1. Conclusions: These data may serve for improved interpretation of new FOXG1 sequence variants and well-founded genetic counseling.
Genetics in medicine Amsterdam : Elsevier, 1998 20(2018), 1, Seite 98-108 Online-Ressource
Oldenburg: BIS-Verl. der Carl von Ossietzky Univ. Oldenburg
XVI, 449 S. graph. Darst. 145 mm x 205 mm.
Beitr. teilw. dt., teilw. engl
Caucasian languages -- Syntax -- Congresses; Grammar, Comparative and general -- Adjuncts -- Congresses; Grammar, Comparative and general -- Syntax -- Congresses; Grammar, Comparative and general -- Verb phrase -- Congresses; Indo-European languages -- Syntax -- Congresses; Slavic languages -- Syntax -- Congresses; Turkic languages -- Syntax -- Congresses; Aufsatzsammlung; KonferenzschriftPrädikationPrädikatSyntaxSatzgliedAussagenlogikApophantik
This volume offers descriptive and theoretical studies on depictive secondary predicates in a wide variety of languages. While the focus is on the Middle and Eastern European area, including Slavonic, Baltic, Finno-Ugric, Turkic and Caucasian languages, and on languages of the Balkan Area, the scope of the collection is widened to studies of secondary predication in German and English, in the languages of Morocco and in Classical Aztec. The chapters deal with typological issues of secondary predicates and their debatable universality, with problems of distinguishing secondary predicates from other syntactic categories, with their syntactic status and their distinctive morphological marking. The published papers evolved from papers read at an international symposium on 'Descriptive an theoretical problems of secondary predicates, with emphasis on Middle and Eastern European languages', held at the University of Oldenburg, December 7-10, 2005. <engl.>
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