Connect with other TFE3 families
TFE3-associated neurodevelopmental disorder – what is it?
TFE3-associated neurodevelopmental disorder (or just TFE3), is a very rare mutation of the X-chromosome linked "transcription factor for immunoglobulin heavy-chain enhancer 3" (TFE3) gene. How rare? There are currently around 30 known cases worldwide, with a few more being identified every year.
Sometimes misdiagnosed as lysosomal storage disorders, it can be properly identified through genetic testing. The medical literature linked-to below goes into more detail on the how and why, but visibly, TFE3 presents primarily as intellectual disability, facial dysmorphism, pigmentary mosaicism (varied patterns of pigmentation in the skin), and seizures. Currently, treatment is limited to alleviation of symptoms and physical therapy to improve mobility, speech, etc, although there are some promising advances being made in gene therapy. Clinical trials are ongoing - more data is always needed.
Since this is such a rare condition, info and resources are a bit scattered; with this page I'm hoping to maintain an archive of anything useful I can find on TFE3, especially to help family and friends of the newly diagnosed. If you are aware of anything that is not linked-to here, please let me know so I can add it. (BTW, please excuse the 90's era formatting - I'm not a web pro, just a guy who learned enough HTML to share some important information!)
IMPORTANT ANNOUNCEMENT! TFE3.org is now live!
A much improved portal of all things TFE3 related for family and friends, geared towards the support of research and awareness, with room to grow as our combined knowledge increases. Including a section specifically for TFE3 families to share their stories. Since TFE3.org contains everything found here plus more, this page (TFE3.info) will go away in the near future - please update your links and bookmarks to TFE3.org
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(I don't have a location for all of the known cases, if you want yours on this map, please email me.)
Connect with other TFE3 families
There is a Facebook TFE3 support group for family and friends; found at:
https://www.facebook.com/groups/tfe3support.
There is also a whats-app group. Both of these resources are highly recommended for any family facing a new TFE3 diagnosis. There are families there of TFE3 kids ranging in age from toddler to teenager. For more information about either, please contact Rainbow Solomon at rainbow@tfe3.infoComing Soon!
We are currently developing a voluntary patient registry to maximize the medical knowlege of this disease that doctors can access. When it becomes available, please consider sharing your experience to this registry - the larger the sample size, the more information that doctors have, the better and more effectively they can treat every child.
Why a Community-Driven Registry?
Personal stories from TFE3 families
Kelley and Ryan's story
https://www.raregenomics.org/news-events-and-blogs/2022/6/4/kelley-and-ryans-story?rq=TFE3
Rare like Ryan youtube channel
https://www.youtube.com/@rarelikeryan
Plan du site - Le petit monde de Thaïs
http://mondedethais.canalblog.com/archives/index.html
Doctors, therapists, other medical professionals with direct TFE3 experience
Published:
Dr Daphné lehalle, Fédération hospitalo-Universitaire Médecine Translationnelle et anomalies du Développement (TranslaD), centre hospitalier, Universitaire Dijon et Université de Bourgogne, Dijon, France; daphne.lehalle@aphp.fr
Working with families:
(Since this is such a rare condition, the few medical professionals that have direct experience can truly be considered the “experts in the field.” Please help me build a “consulting list” so all our Doctors can work together to build a knowledge base.)
Assorted genetic and rare desease networks/specialists/resources
(I'm currently aware of primarily USA based organizations, please let me know of any I should add, particularly what is available in other countries)
GARD - Genetic and Rare Diseases Information Center (National Institutes of Health)
https://rarediseases.info.nih.gov/
NCATS - National Center for Advancing Translational Sciences (National Institutes of Health)
https://ncats.nih.gov/
Consultagene (Baylor College of Medicine)
https://consultagene.com/
Rare Genomics Institute
https://www.raregenomics.org/
Mount Sinai Genetic Outreach (Mount Sinai Hospital)
https://www.mountsinai.org/care/genetics
NORD - National Organization for Rare Disorders
https://rarediseases.org/
Undiagnosed Diseases Network (Harvard University)
https://undiagnosed.hms.harvard.edu/
OTP - Office of Theraputic Products, Cellular & Gene Therapy Products (US FDA)
https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products
How Gene Therapy Works (US FDA)
https://www.fda.gov/consumers/consumer-updates/how-gene-therapy-can-cure-or-treat-diseases?%20how%20does%20it%20work?
Genomics England PanelApp (NHS)
https://panelapp.genomicsengland.co.uk/
EveryLife Foundation for Rare Diseases
https://everylifefoundation.org
n-lorem Foundation
https://www.nlorum.org/patient-empowerment/
Medical literature (Some of these require a subscription to view the entire document)
TFE3-associated neurodevelopmental disorder:
TFE3-associated neurodevelopmental disorder: A distinct recognizable syndrome (National Institutes of Health)
https://pubmed.ncbi.nlm.nih.gov/31833172/
De novo mutations in the X-linked TFE3 gene cause intellectual disability with pigmentary mosaicism and storage disorder-like features (National Institutes of Health)
https://jmg.bmj.com/content/jmedgenet/57/12/808.full.pdf
Lysosomal Signaling Licenses Embryonic Stem Cell Differentiation via Inactivation of Tfe3 (National Institutes of Health)
https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(18)30557-5?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1934590918305575%3Fshowall%3Dtrue
TFE3-Associated Neurodevelopmental Disorder (TFE3) (Rare Genomics Institute)
https://www.raregenomics.org/tfe3-associated-neurodevelopmental-disorder-tfe3
Transcription Factor for Immunoglobulin Heavy-Chain Enhancer 3; TFE3 (OMIM)
https://www.omim.org/entry/314310
Gene: TFE3 (Genomics England PanelApp)
https://panelapp.genomicsengland.co.uk/panels/402/gene/TFE3/
Additional TFE3 genetic info and non-related TFE3 gene research:
TFE3 Gene (GeneCards Human Gene Database)
https://www.genecards.org/cgi-bin/carddisp.pl?gene=TFE3
TFE3 (Wikipedia)
https://en.wikipedia.org/wiki/TFE3
P19532 TFE3_Human (UniProt)
https://www.uniprot.org/uniprotkb/P19532/entry
Nutrient-sensitive transcription factors TFEB and TFE3 couple autophagy and metabolism to the peripheral clock (National Institutes of Health)
https://pubmed.ncbi.nlm.nih.gov/31126958/
TFEB and TFE3, Linking Lysosomes to Cellular Adaptation to Stress (National Institutes of Health)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6490169/
Emerging roles of TFE3 in metabolic regulation (CDD Press)
https://www.nature.com/articles/s41420-023-01395-0
TFE3 transcription factor binding to IGHM enhancer 3 [Homo sapiens (human)] (National Library of Medicine)
https://www.ncbi.nlm.nih.gov/gene/7030
Human Gene TFE3 (uc004dmb.3) (UCSC Genomics Institute)
https://genome.ucsc.edu/cgi-bin/hgGene?db=hg19&hgg_gene=TFE3
Ragulator—a multifaceted regulator of lysosomal signaling and trafficking (Journal of Cell Biology)
https://rupress.org/jcb/article/216/12/3895/38867/Ragulator-a-multifaceted-regulator-of-lysosomal
The lysosome as a command-and-control center for cellular metabolism (Journal of Cell Biology)
https://rupress.org/jcb/article/214/6/653/38688/The-lysosome-as-a-command-and-control-center-for
The Rag GTPases-mTORC1-TFE3 Axis in Kidney Cancer and Neurodevelopment: A Mini Review (Journal of Neurology & Neuromedicine)
https://www.jneurology.com/articles/the-rag-gtpases-mtorc1-tfe3-axis-in-kidney-cancer-and-neurodevelopment-a-mini-review.html
Please email me with any additions / updates.
Most recent update: September 16, 2024