Diegmann, Susann

[["dc.bibliographiccitation.artnumber","awac154"],["dc.bibliographiccitation.journal","Brain"],["dc.contributor.author","Wong, Keit Men"],["dc.contributor.author","Jepsen, Wayne M"],["dc.contributor.author","Efthymiou, Stephanie"],["dc.contributor.author","Salpietro, Vincenzo"],["dc.contributor.author","Sanchez-Castillo, Meredith"],["dc.contributor.author","Yip, Janice"],["dc.contributor.author","Kriouile, Yamna"],["dc.contributor.author","Diegmann, Susann"],["dc.contributor.author","Dreha-Kulaczewski, Steffi"],["dc.contributor.author","Altmüller, Janine"],["dc.contributor.author","Huppke, Peter"],["dc.date.accessioned","2022-07-01T07:35:01Z"],["dc.date.available","2022-07-01T07:35:01Z"],["dc.date.issued","2022"],["dc.description.abstract","Abstract TAF8 is part of the transcription factor II D complex, composed of the TATA-binding protein and 13 TATA-binding protein–associated factors (TAFs). Transcription factor II D is the first general transcription factor recruited at promoters to assemble the RNA polymerase II preinitiation complex. So far disorders related to variants in 5 of the 13 subunits of human transcription factor II D have been described. Recently, a child with a homozygous c.781-1G>A mutation in TAF8 has been reported. Here we describe seven further patients with mutations in TAF8 and thereby confirm the TAF8 related disorder. In two sibling patients, we identified two novel compound heterozygous TAF8 splice site mutations, c.45+4A > G and c.489G>A, which cause aberrant splicing as well as reduced expression and mislocalization of TAF8. In five further patients, the previously described c.781-1G > A mutation was present on both alleles. The clinical phenotype associated with the different TAF8 mutations is characterized by severe psychomotor retardation with almost absent development, feeding problems, microcephaly, growth retardation, spasticity and epilepsy. Cerebral imaging showed hypomyelination, a thin corpus callosum and brain atrophy. Moreover, repeated imaging in the sibling pair demonstrated progressive cerebral and cerebellar atrophy. Consistently, reduced N-acetylaspartate, a marker of neuronal viability, was observed on magnetic resonance spectroscopy. Further review of the literature shows that mutations causing a reduced expression of transcription factor II D subunits have an overlapping phenotype of microcephaly, developmental delay and intellectual disability. Although transcription factor II D plays an important role in RNA polymerase II transcription in all cells and tissues, the symptoms associated with such defects are almost exclusively neurological. This might indicate a specific vulnerability of neuronal tissue to widespread deregulation of gene expression as also seen in Rett syndrome or Cornelia de Lange syndrome."],["dc.identifier.doi","10.1093/brain/awac154"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/112066"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-581"],["dc.relation.eissn","1460-2156"],["dc.relation.issn","0006-8950"],["dc.title","Mutations in TAF8 cause a neurodegenerative disorder"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2803"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","American Journal of Medical Genetics Part A"],["dc.bibliographiccitation.lastpage","2807"],["dc.bibliographiccitation.volume","173"],["dc.contributor.author","Weissbach, Susann"],["dc.contributor.author","Reinert, Marie-Christine"],["dc.contributor.author","Altmüller, Janine"],["dc.contributor.author","Krätzner, Ralph"],["dc.contributor.author","Thiele, Holger"],["dc.contributor.author","Rosenbaum, Thorsten"],["dc.contributor.author","Nürnberg, Peter"],["dc.contributor.author","Gärtner, Jutta"],["dc.date.accessioned","2018-04-23T11:47:26Z"],["dc.date.available","2018-04-23T11:47:26Z"],["dc.date.issued","2017"],["dc.description.abstract","Cabezas type of X‐linked syndromic intellectual disability (MRXSC; MIM300354) is a rare X‐linked recessive intellectual disability characterized primarily by intellectual disability, short stature, hypogonadism, and gait abnormalities. It is caused by a wide spectrum of hemizygous variants in CUL4B. In a 10‐year‐old boy with an exceptional leukoencephalopathy pattern, we identified a new missense variant p.Leu329Gln in CUL4B using “Mendeliome” sequencing. However, his phenotype does not include the severe characteristics currently known for MRXSC. We discuss the divergent phenotype and propose a potential connection between the different CUL4B variants and corresponding phenotypes in the context of the current literature as well as 3D homology modeling."],["dc.identifier.doi","10.1002/ajmg.a.38390"],["dc.identifier.gro","3142217"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/13339"],["dc.language.iso","en"],["dc.notes.intern","lifescience updates Crossref Import"],["dc.notes.status","final"],["dc.relation.issn","1552-4825"],["dc.title","A new CUL4B variant associated with a mild phenotype and an exceptional pattern of leukoencephalopathy"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","ajmg.a.62852"],["dc.bibliographiccitation.journal","American Journal of Medical Genetics Part A"],["dc.contributor.author","Musante, Luciana"],["dc.contributor.author","Faletra, Flavio"],["dc.contributor.author","Meier, Kolja"],["dc.contributor.author","Tomoum, Hoda"],["dc.contributor.author","Najarzadeh Torbati, Paria"],["dc.contributor.author","Blair, Edward"],["dc.contributor.author","North, Sally"],["dc.contributor.author","Gärtner, Jutta"],["dc.contributor.author","Diegmann, Susann"],["dc.contributor.author","Beiraghi Toosi, Mehran"],["dc.contributor.author","Carrozzi, Marco"],["dc.date.accessioned","2022-07-01T07:35:37Z"],["dc.date.available","2022-07-01T07:35:37Z"],["dc.date.issued","2022"],["dc.identifier.doi","10.1002/ajmg.a.62852"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/112217"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-581"],["dc.relation.eissn","1552-4833"],["dc.relation.issn","1552-4825"],["dc.rights.uri","http://creativecommons.org/licenses/by-nc-nd/4.0/"],["dc.title","TTC5 syndrome: Clinical and molecular spectrum of a severe and recognizable condition"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","818"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Huppke, Peter"],["dc.contributor.author","Weissbach, Susann"],["dc.contributor.author","Church, Joseph A."],["dc.contributor.author","Schnur, Rhonda"],["dc.contributor.author","Krusen, Martina"],["dc.contributor.author","Dreha-Kulaczewski, Steffi"],["dc.contributor.author","Kühn-Velten, W. Nikolaus"],["dc.contributor.author","Wolf, Annika"],["dc.contributor.author","Huppke, Brenda"],["dc.contributor.author","Millan, Francisca"],["dc.contributor.author","Begtrup, Amber"],["dc.contributor.author","Almusafri, Fatima"],["dc.contributor.author","Thiele, Holger"],["dc.contributor.author","Altmüller, Janine"],["dc.contributor.author","Nürnberg, Peter"],["dc.contributor.author","Müller, Michael"],["dc.contributor.author","Gärtner, Jutta"],["dc.date.accessioned","2018-04-23T11:47:26Z"],["dc.date.available","2018-04-23T11:47:26Z"],["dc.date.issued","2017"],["dc.description.abstract","Transcription factor NRF2, encoded by NFE2L2, is the master regulator of defense against stress in mammalian cells. Somatic mutations of NFE2L2 leading to NRF2 accumulation promote cell survival and drug resistance in cancer cells. Here we show that the same mutations as inborn de novo mutations cause an early onset multisystem disorder with failure to thrive, immunodeficiency and neurological symptoms. NRF2 accumulation leads to widespread misregulation of gene expression and an imbalance in cytosolic redox balance. The unique combination of white matter lesions, hypohomocysteinaemia and increased G-6-P-dehydrogenase activity will facilitate early diagnosis and therapeutic intervention of this novel disorder."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2017"],["dc.identifier.doi","10.1038/s41467-017-00932-7"],["dc.identifier.gro","3142218"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14817"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/13340"],["dc.language.iso","en"],["dc.notes.intern","lifescience updates Crossref Import"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.relation.issn","2041-1723"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Activating de novo mutations in NFE2L2 encoding NRF2 cause a multisystem disorder"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]