Phänotyp-Analyse und Genotyp-Phänotyp-Assoziationen bei 83 mit FOXG1-Syndrom

Phenotyp-analysis and genotype–phenotype association in 83 patients with FOXG1 syndrome

by Kim Sarah Plümacher
Doctoral thesis
Date of Examination:2019-05-22
Date of issue:2019-05-13
Advisor:Prof. Dr. Knut Brockmann
Referee:Prof. Dr. Peter Burfeind
Referee:Prof. Dr. Margarete Schön
Persistent Address: http://dx.doi.org/10.53846/goediss-7427

 

 

Files in this item

Name:EDISS_pluemacher_bearb.pdf
Size:7.39Mb
Format:PDF

The following license files are associated with this item:

Abstract

English

Purpose: The aim of this study was to increase the knowlegde about the clinical spectrum and to evaluate genotyp-phenotyp associations in FOXG1 syndrome due to FOXG1 variants. Methods: We recruited 30 new and 53 reported patients with a heterozygous pathogenic or likely pathogenic variant in FOXG1. For the phenotyp-genotyp association we grouped them depending on type and location oft he variant. By using Fisher's exact test and a nonparametric multivariate test statistic analysis of clinical and gentic features was performed. Based on the results we designed a severity score to objectify the intensitiy oft he FOXG1 Syndrom each patient.  Results: In all 83 patients there were 54 different FOXG1 variants and among them 19 variants were novel. We demonstrate a higher phneotypic variability than previously described. In psychomotor development and neurological characteristics we found significant differences by comparing the FOXG1 genotyp groups. Patients with truncation FOXG1 variants in the N-terminal domain and the forkhead domain (except conserved site 1) have more severe phenotypes.  Milder phenotyps were found in patients with missense variants in the forkhead conserved site 1. The results severity score results correspond with the results of the genotyp-phenotyp analysis.  Conclusions: These data improve the knowledge about the clinical and genetic spectrum in patients with FOXG1 syndrom. Furthermore it may improve the interpretation of different FOXG1 variants and gives a foundation for genetic counseling. 
Keywords: FOXG1 syndrome
Schlagwörter: FOXG1 Syndrom
 
Statistik