Current Research

Development of novel therapeutics for the treatment of myeloid malignancies and skeletal deficits

Research Interest of Feng-Chun Yang, M.D., PhD, Professor Sylvester Comprehensive Cancer Center Department of Biochemistry and Molecular Biology, University of Miami:

  • Role of ASXL1 and NF1 in the pathogenesis of myeloid malignancies
  • Role of bone marrow niche in the pathogenesis of myeloid malignancies (FA and NF1)
  • Development of novel therapeutics for the treatment of myeloid malignancies (FA and NF1) and skeletal deficits (NF1, Bohring-Opitz Syndrome –ASXL1 mutation)

More information on this Research Interest of Feng-Chun Yang you can find here.


Clinical and molecular genetics study of Bohring Opitz syndrome

The human physiopathology study, registered under Orpha number ORPHA234667 is investigated by:
Department of Clinical Genetics
University Hospitals Bristol

Developmental disease or cancer: the crucial role of timing and type of new mutations

In this project Rocío Acuña HidalgoAlexander HoischenJoris Veltman hypothesize that mainly two factors influence the seemingly dual role of developmental disease genes: first, the timing of the mutational process determines whether mutations cause a developmental disorder (if mutated constitutionally) or cancer (if mutated somatically); second, the mutation type influences the outcome as different genetic alterations may, for example, result in a gain or loss of function, which impacts on the molecular and clinical phenotype.

One cause of  Bohring-Opitz Syndrome is novo ASXL1 mutation: This gene mutates at conception, creating a developmental disorder that leads to Bohring-Opitz Syndrome.
The somatic ASXL1 mutation occurs during later life. The patient has an increased risk of acute myeloid leukaemia, a form of blood cancer (AML).[4]

They will follow up several developmental disorders, such as Bohring-Opitz syndrome and Schinzel-Giedeon syndrome.

Read more about this project.

Research of Opitz C Syndrome

Geneticists at Universitat de Barcelona in Barcelona, Spain are investigate into the genetic cause of the disease Opitz C Syndrome (OMIM Entry #211750). Together with Drs John Opitz and Giovanni Neri they established a collaboration to share expertises and samples of several patients affected with Opitz C Syndrome or Bohring Opitz syndrome (BOS).

You can find further information to this current research on the blog Science and Spice… from Dr. Roser Urreizti.

You could also see the video of the campaign (in Spanish) here:

Read more about Opitz C Syndrome here.

The role of Asxls in Bohring-Opitz-Syndrome

Public Abstract

PhD student: Friederike Matheus
Project leader and group leader: Dr. Micha Drukker
Group of Human Pluripotent Stem Cell Differentiation
Helmholtz Zentrum Muenchen

Up until 2013, only mutations in the Asxl1 gene have been linked to Bohring-Opitz Syndrome (BOS). These mutations code for dysfunctional ASXL1 proteins (1, 2). Recently, mutations in an additional member of the Asxl gene family, Asxl3, has been associated with cases of BOS-like syndrome (3).  Since BOS is a congenital disease that exhibits a broad spectrum of defects, we hypothesized that the ASXL proteins, probably together with other factors, play a crucial role in the very first stages of life. Therefore, to shed light on BOS, we work on discovering the functions of ASXLs in normal human development and in models of BOS. It occurred to us that the ideal model for BOS would be one that is based on human pluripotent stem cells that are generated by reprogramming of patient skin cells. The reprogramming process produces human embryonic-like cells, known as induced pluripotent stem cells (iPS cells), which can be differentiated in tissue culture for imitating human embryonic and fetal development. Such iPS cells and differentiation protocols can be used as a system to study the mechanisms of BOS.

To achieve these goals we make use of state-of-the-art molecular biology techniques for reprogramming. We begin with very small skin biopsies from BOS patients, producing patient specific iPS cell lines within several weeks. Then we analyze molecular pathways that are perturbed by the mutations in Asxl1 during differentiation of patient iPS cells. We investigate genetic and epigenetic pathways; this means that we analyze how Asxls control gene expression of embryonic genes, and how mutations in Asxls disrupt control of gene expression and protein function. Our prospect for this project is that it will shed light into what is “going wrong” in the developmental progress of BOS patients, and we hope that this knowledgebase in turn will allow us to develop therapies for BOS. Since so little is known about the mechanisms that underlie BOS, we feel that basic studies of BOS on the cellular level are necessary for therapeutic breakthroughs.

Our research group is located in the Helmholtz Center Munich, and we are deeply interested in broadening our patient sample panel, and in information about patients that can assist us in understudying BOS. Therefore we would be thankful for communications with families as well as physicians and geneticists.

Please don’t hesitate to contact: Friederike Matheus

(1) Hoischen A et al. (2011) De novo nonsense mutations in ASXL1 cause Bohring-Opitz syndrome. Nat Genet. 43(8):729-31.
(2) Magini P et al. (2012) Two novel patients with Bohring-Opitz syndrome caused by de novo ASXL1 mutations. Am J Med Genet A. 158A(4):917-21.
(3) Bainbridge MN et al. (2013) De novo truncating mutations in ASXL3 are associated with a novel clinical phenotype with similarities to Bohring-Opitz syndrome. Genome Med. 5(2):11.

Print The role of Asxls in Bohring-Opitz-Syndrome – Public AbstractBOS-Text MD-Helmholtz Center Munich.

Bainbridge-Ropers Syndrome study

Currently there is a study at the Baylor College of Medicine about the Bainbridge-Ropers Syndrome. This purpose of this study, under leadership of Matthew Bainbridge, is to collect clinical information to more clearly define the phenotypic spectrum of this disorder and to perform genotype phenotype correlations.

The children have phenotypes similar to BOS, including severe feeding difficulties, failure-to-thrive and neurologic abnormalities with significant developmental delay. Further, they showed less phenotypic overlap with patients who had de novo truncating mutations in ASXL1 (Bainbridge et al. 2013).

Bainbridge-Ropers Syndrome study

Read more about Bainbridge-Ropers Syndrome here.