Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Jan;20(1):98-108.
doi: 10.1038/gim.2017.75. Epub 2017 Jun 29.

FOXG1 syndrome: genotype-phenotype association in 83 patients with FOXG1 variants

Diana Mitter  1 , Milka Pringsheim  2   3 , Marc Kaulisch  4 , Kim Sarah Plümacher  5 , Simone Schröder  5 , Rita Warthemann  5 , Rami Abou Jamra  1 , Martina Baethmann  6 , Thomas Bast  7 , Hans-Martin Büttel  8 , Julie S Cohen  9 , Elizabeth Conover  10 , Carolina Courage  11 , Angelika Eger  12 , Ali Fatemi  9 , Theresa A Grebe  13 , Natalie S Hauser  14 , Wolfram Heinritz  15 , Katherine L Helbig  16 , Marion Heruth  17 , Dagmar Huhle  18 , Karen Höft  19 , Stephanie Karch  20 , Gerhard Kluger  2   3 , G Christoph Korenke  21 , Johannes R Lemke  1 , Richard E Lutz  10 , Steffi Patzer  22 , Isabelle Prehl  23 , Konstanze Hoertnagel  23 , Keri Ramsey  24 , Tina Rating  25 , Angelika Rieß  26 , Luis Rohena  27 , Mareike Schimmel  28 , Rachel Westman  29 , Frank-Martin Zech  30 , Barbara Zoll  31 , Dörthe Malzahn  32 , Birgit Zirn  33 , Knut Brockmann  34
Affiliations
Free article

FOXG1 syndrome: genotype-phenotype association in 83 patients with FOXG1 variants

Diana Mitter et al. Genet Med. 2018 Jan.
Free article

Abstract

PurposeThe study aimed at widening the clinical and genetic spectrum and assessing genotype-phenotype associations in FOXG1 syndrome due to FOXG1 variants.MethodsWe 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.ResultsAmong 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.ConclusionsThese data may serve for improved interpretation of new FOXG1 sequence variants and well-founded genetic counseling.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Am J Med Genet. 1993 Nov 15;47(7):940-6 - PubMed
    1. Hum Mutat. 2006 Apr;27(4):389 - PubMed
    1. Eur J Paediatr Neurol. 2014 May;18(3):420-6 - PubMed
    1. Genet Med. 2016 Jul;18(7):696-704 - PubMed
    1. Eur J Med Genet. 2009 Nov-Dec;52(6):440-2 - PubMed

Publication types

Substances

LinkOut - more resources