Home > Publications Database > Bi-allelic loss-of-function variants in BCAS3 cause a syndromic neurodevelopmental disorder. > print

001     155888
005     20240124115011.0
024 7 _ |a 10.1016/j.ajhg.2021.04.024
|2 doi
024 7 _ |a pmid:34022130
|2 pmid
024 7 _ |a pmc:PMC8206390
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024 7 _ |a 0002-9297
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024 7 _ |a 1537-6605
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024 7 _ |a altmetric:106226451
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037 _ _ |a DZNE-2021-01048
041 _ _ |a English
082 _ _ |a 570
100 1 _ |a Hengel, Holger
|0 P:(DE-2719)2811940
|b 0
|e First author
|u dzne
245 _ _ |a Bi-allelic loss-of-function variants in BCAS3 cause a syndromic neurodevelopmental disorder.
260 _ _ |a New York, NY
|c 2021
|b Elsevier
336 7 _ |a article
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336 7 _ |a Output Types/Journal article
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336 7 _ |a Journal Article
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|s 1706014569_18612
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336 7 _ |a ARTICLE
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336 7 _ |a Journal Article
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520 _ _ |a BCAS3 microtubule-associated cell migration factor (BCAS3) is a large, highly conserved cytoskeletal protein previously proposed to be critical in angiogenesis and implicated in human embryogenesis and tumorigenesis. Here, we established BCAS3 loss-of-function variants as causative for a neurodevelopmental disorder. We report 15 individuals from eight unrelated families with germline bi-allelic loss-of-function variants in BCAS3. All probands share a global developmental delay accompanied by pyramidal tract involvement, microcephaly, short stature, strabismus, dysmorphic facial features, and seizures. The human phenotype is less severe compared with the Bcas3 knockout mouse model and cannot be explained by angiogenic defects alone. Consistent with being loss-of-function alleles, we observed absence of BCAS3 in probands' primary fibroblasts. By comparing the transcriptomic and proteomic data based on probands' fibroblasts with those of the knockout mouse model, we identified similar dysregulated pathways resulting from over-representation analysis, while the dysregulation of some proposed key interactors could not be confirmed. Together with the results from a tissue-specific Drosophila loss-of-function model, we demonstrate a vital role for BCAS3 in neural tissue development.
536 _ _ |a 353 - Clinical and Health Care Research (POF4-353)
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650 _ 7 |a BCAS3
|2 Other
650 _ 7 |a UAS-Gal4
|2 Other
650 _ 7 |a fibroblasts
|2 Other
650 _ 7 |a global developmental delay
|2 Other
650 _ 7 |a microcephaly
|2 Other
650 _ 7 |a neurodevelopmental disorder
|2 Other
650 _ 7 |a proteomics
|2 Other
650 _ 7 |a pyramidal tract involvement
|2 Other
650 _ 7 |a thin corpus callosum
|2 Other
650 _ 7 |a transcriptomics
|2 Other
650 _ 7 |a BCAS3 protein, human
|2 NLM Chemicals
650 _ 7 |a Neoplasm Proteins
|2 NLM Chemicals
650 _ 7 |a Proteome
|2 NLM Chemicals
650 _ 2 |a Adolescent
|2 MeSH
650 _ 2 |a Adult
|2 MeSH
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Cell Movement
|2 MeSH
650 _ 2 |a Child
|2 MeSH
650 _ 2 |a Child, Preschool
|2 MeSH
650 _ 2 |a Drosophila
|2 MeSH
650 _ 2 |a Female
|2 MeSH
650 _ 2 |a Fibroblasts: metabolism
|2 MeSH
650 _ 2 |a Fibroblasts: pathology
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Infant
|2 MeSH
650 _ 2 |a Loss of Function Mutation
|2 MeSH
650 _ 2 |a Loss of Heterozygosity
|2 MeSH
650 _ 2 |a Male
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Mice, Knockout
|2 MeSH
650 _ 2 |a Neoplasm Proteins: genetics
|2 MeSH
650 _ 2 |a Neoplasm Proteins: metabolism
|2 MeSH
650 _ 2 |a Neurodevelopmental Disorders: etiology
|2 MeSH
650 _ 2 |a Neurodevelopmental Disorders: metabolism
|2 MeSH
650 _ 2 |a Neurodevelopmental Disorders: pathology
|2 MeSH
650 _ 2 |a Pedigree
|2 MeSH
650 _ 2 |a Proteome: analysis
|2 MeSH
650 _ 2 |a Young Adult
|2 MeSH
700 1 _ |a Hannan, Shabab B
|0 P:(DE-2719)9000570
|b 1
|u dzne
700 1 _ |a Dyack, Sarah
|b 2
700 1 _ |a MacKay, Sara B
|b 3
700 1 _ |a Schatz, Ulrich
|b 4
700 1 _ |a Fleger, Martin
|b 5
700 1 _ |a Kurringer, Andreas
|b 6
700 1 _ |a Balousha, Ghassan
|b 7
700 1 _ |a Ghanim, Zaid
|b 8
700 1 _ |a Alkuraya, Fowzan S
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700 1 _ |a Alzaidan, Hamad
|b 10
700 1 _ |a Alsaif, Hessa S
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700 1 _ |a Mitani, Tadahiro
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700 1 _ |a Bozdogan, Sevcan
|b 13
700 1 _ |a Pehlivan, Davut
|b 14
700 1 _ |a Lupski, James R
|b 15
700 1 _ |a Gleeson, Joseph J
|b 16
700 1 _ |a Dehghani, Mohammadreza
|b 17
700 1 _ |a Mehrjardi, Mohammad Y V
|b 18
700 1 _ |a Sherr, Elliott H
|b 19
700 1 _ |a Parks, Kendall C
|b 20
700 1 _ |a Argilli, Emanuela
|b 21
700 1 _ |a Begtrup, Amber
|b 22
700 1 _ |a Galehdari, Hamid
|b 23
700 1 _ |a Balousha, Osama
|b 24
700 1 _ |a Shariati, Gholamreza
|b 25
700 1 _ |a Mazaheri, Neda
|b 26
700 1 _ |a Malamiri, Reza A
|b 27
700 1 _ |a Pagnamenta, Alistair T
|b 28
700 1 _ |a Kingston, Helen
|b 29
700 1 _ |a Banka, Siddharth
|b 30
700 1 _ |a Jackson, Adam
|b 31
700 1 _ |a Osmond, Mathew
|b 32
700 1 _ |a Consortium, Care4Rare Canada
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700 1 _ |a Consortium, Genomics England Research
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700 1 _ |a Rieß, Angelika
|b 35
700 1 _ |a Haack, Tobias B
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700 1 _ |a Nägele, Thomas
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700 1 _ |a Schuster, Stefanie
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700 1 _ |a Hauser, Stefan
|0 P:(DE-2719)2810998
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700 1 _ |a Admard, Jakob
|b 40
700 1 _ |a Casadei, Nicolas
|b 41
700 1 _ |a Velic, Ana
|b 42
700 1 _ |a Macek, Boris
|b 43
700 1 _ |a Ossowski, Stephan
|b 44
700 1 _ |a Houlden, Henry
|b 45
700 1 _ |a Maroofian, Reza
|b 46
700 1 _ |a Schöls, Ludger
|0 P:(DE-2719)2810795
|b 47
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773 _ _ |a 10.1016/j.ajhg.2021.04.024
|g Vol. 108, no. 6, p. 1069 - 1082
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|t The American journal of human genetics
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