De novo nonsense mutations in ASXL1 cause Bohring-Opitz syndrome

被引:207
|
作者
Hoischen, Alexander [1 ]
van Bon, Bregje W. M. [1 ]
Rodriguez-Santiago, Benjamin [1 ,2 ,3 ]
Gilissen, Christian [1 ]
Vissers, Lisenka E. L. M. [1 ]
de Vries, Petra [1 ]
Janssen, Irene [1 ]
van Lier, Bart [1 ]
Hastings, Rob [4 ]
Smithson, Sarah F. [4 ]
Newbury-Ecob, Ruth [4 ]
Kjaergaard, Susanne [5 ]
Goodship, Judith [6 ]
McGowan, Ruth [7 ]
Bartholdi, Deborah [8 ]
Rauch, Anita [8 ]
Peippo, Maarit [9 ]
Cobben, Jan M. [10 ]
Wieczorek, Dagmar [11 ]
Gillessen-Kaesbach, Gabriele [12 ]
Veltman, Joris A. [1 ]
Brunner, Han G. [1 ]
de Vries, Bert B. B. A. [1 ]
机构
[1] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands
[2] Univ Pompeu Fabra, Dept Ciencies Expt & Salut, Barcelona, Spain
[3] CIBERER, Barcelona, Spain
[4] St Michaels Hosp, Dept Clin Genet, Bristol, Avon, England
[5] Rigshosp, Univ Copenhagen Hosp, Dept Clin Genet, Copenhagen, Denmark
[6] Newcastle Univ, Inst Human Genet, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England
[7] Yorkhill Hosp, Dept Med Genet, Glasgow, Lanark, Scotland
[8] Univ Zurich, Inst Med Genet, CH-8603 Schwerzenbach, Switzerland
[9] Family Federat Finland, Dept Med Genet, Helsinki, Finland
[10] Emma Kinderziekenhuis Acad Med Ctr AMC, Dept Pediat Genet, Amsterdam, Netherlands
[11] Univ Klinikum Essen, Inst Humangenet, Essen, Germany
[12] Univ Lubeck, Inst Humangenet Lubeck, Lubeck, Germany
关键词
TRIGONOCEPHALY SYNDROME; VARIANTS; LEUKEMIA;
D O I
10.1038/ng.868
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Bohring-Opitz syndrome is characterized by severe intellectual disability, distinctive facial features and multiple congenital malformations. We sequenced the exomes of three individuals with Bohring-Opitz syndrome and in each identified heterozygous de novo nonsense mutations in ASXL1, which is required for maintenance of both activation and silencing of Hox genes. In total, 7 out of 13 subjects with a Bohring-Opitz phenotype had de novo ASXL1 mutations, suggesting that the syndrome is genetically heterogeneous.
引用
收藏
页码:729 / 731
页数:3
相关论文
共 50 条
  • [41] Extending the phenotypic spectrum of Bohring-Opitz syndrome: Mild case confirmed by functional studies
    Leon, Eyby
    Diaz, Jullianne
    Castilla-Vallmanya, Laura
    Grinberg, Daniel
    Balcells, Susanna
    Urreizti, Roser
    AMERICAN JOURNAL OF MEDICAL GENETICS PART A, 2020, 182 (01) : 201 - 204
  • [42] A de novo truncating mutation in ASXL1 associated with segmental overgrowth
    Stephanie Efthymiou
    Vincenzo Salpietro
    Erica Pironti
    Maria Bonsignore
    Valentina Ferrazzoli
    Gabriella Di Rosa
    Henry Houlden
    Journal of Genetics, 2019, 98
  • [43] A de novo truncating mutation in ASXL1 associated with segmental overgrowth
    Efthymiou, Stephanie
    Salpietro, Vincenzo
    Pironti, Erica
    Bonsignore, Maria
    Ferrazzoli, Valentina
    Di Rosa, Gabriella
    Houlden, Henry
    JOURNAL OF GENETICS, 2019, 98 (05)
  • [44] Self-Induced Bilateral Retinal Detachments and Traumatic Cataracts in a Patient With Bohring-Opitz Syndrome
    Hanes, Madeline
    Rahman, Effie Z.
    Wong, Robert W.
    Harper, C. Armitage
    OPHTHALMIC SURGERY LASERS & IMAGING RETINA, 2021, 52 (07): : 400 - 402
  • [45] Loss of Asxl1 Alters Self-Renewal and Cell Fate of Bone Marrow Stromal Cells, Leading to Bohring-Opitz-like Syndrome in Mice
    Zhang, Peng
    Xing, Caihong
    Rhodes, Steven D.
    He, Yongzheng
    Deng, Kai
    Li, Zhaomin
    He, Fuhong
    Zhu, Caiying
    Lihn Nguyen
    Zhou, Yuan
    Chen, Shi
    Mohammad, Khalid S.
    Guise, Theresa A.
    Abdel-Wahab, Omar
    Xu, Mingjiang
    Wang, Qian-Fei
    Yang, Feng-Chun
    STEM CELL REPORTS, 2016, 6 (06): : 914 - 925
  • [46] ASXL1 mutations gain a function
    Kitamura, Toshio
    BLOOD, 2018, 131 (03) : 274 - 275
  • [47] Bohring-Opitz syndrome: Unraveling neonatal hypoglycemia and early detection through whole exome sequencing
    Lin, Ching-Ming
    Lin, Chien-Ming
    Ho, Sheng-Yuan
    PEDIATRICS AND NEONATOLOGY, 2024, 65 (06): : 599 - 600
  • [48] Gaining a Better "Sense" for ASXL1 Mutations in Myelofibrosis: Assessing the Variable Impact of Frameshift, Nonsense, and Missense Mutations
    Kuykendall, Andrew
    Kaplan, Jori L.
    Talati, Chetasi
    Al Ali, Najla
    Sweet, Kendra L.
    Sallman, David A.
    Padron, Eric
    Lancet, Jeffrey E.
    List, Alan F.
    Zuckerman, Kenneth S.
    Komrokji, Rami S.
    BLOOD, 2017, 130
  • [49] EZH2 MUTATION INTERACTS CLOSELY WITH ASXL1 AND AML1/RUNX1 MUTATIONS IN PATIENTS WITH de novo MYELODYSPLASTIC SYNDROME
    Chuang, M. K.
    Hou, H. A.
    Kuo, Y. Y.
    Chou, W. C.
    Lee, M. C.
    Chen, C. Y.
    Lai, Y. J.
    Tseng, M. H.
    Huang, C. F.
    Chiang, Y. C.
    Lee, F. Y.
    Liu, M. C.
    Liu, C. W.
    Tang, J. L.
    Yao, M.
    Huang, S. Y.
    Ko, B. S.
    Hsu, S. C.
    Wu, S. J.
    Lin, C. T.
    Li, C. C.
    Tsay, W.
    Chen, Y. C.
    Tien, H. F.
    HAEMATOLOGICA, 2012, 97 : 131 - 132
  • [50] ASXL1/2 mutations and myeloid malignancies
    Edward A. Medina
    Caroline R. Delma
    Feng-Chun Yang
    Journal of Hematology & Oncology, 15