A*STAR Release: Gene Mutation Discovered To Cause Severe Growth Retardation In Newly Discovered Disease

SINGAPORE, 12 OCTOBER 2017 – Scientists at Singapore’s Agency for Science, Technology and Research (A*STAR), together with collaborators from Europe, USA, and the Middle East, have identified a rare developmental disease and the gene mutation that causes it. The disease is characterised by severe growth retardation, spine malformation, facial dysmorphisms, and intellectual disabilities. The findings were published in The American Journal of Human Genetics on September 7, 2017.

The team of researchers identified nine affected individuals from five unrelated families who were all afflicted by the same syndrome, which is now named the Al Kaissi Syndrome after the clinician in the team who described it first. The team found that mutations in the CDK10 gene are responsible for causing the disease. The protein kinases known as CDKs play critical roles in cell-cycle control, transcription, and development. This finding will help researchers better understand the manner of development of the disease, with the aim of possible therapeutic interventions.

Beyond helping those suffering from the syndrome, the team’s findings could have wider implications for cancer research. A knockout of the CDK10 gene in mice revealed that while loss of CDK10 is detrimental during development, it has little to no effect when occurring during adulthood. Based on this theory that drugs targeting CDK10 would not affect normal adult cells or tissues, the researchers plan to explore the potential of CDK10 as a cancer drug target given that high expression of CDK10 has been linked to various types of cancer, including colorectal and breast cancer.

The research was conducted by a 37-man team, comprising international experts from various fields including clinicians, geneticists, and cell biologists, and was led by Dr Philipp Kaldis from the Institute of Molecular and Cell Biology (IMCB) and Prof Bruno Reversade from the Institute of Medical Biology (IMB). Speaking on the team’s findings, Dr Kaldis, Senior Principal Investigator (PI) at IMCB, said: “To date, very few mutations have been discovered in CDKs. This is why our findings are so novel and could certainly have broader implications for research in other fields, including cancer.”

Prof Reversade, Research Director at IMB and Joint PI at IMCB, added: “There is great value to annotating the human genome using Mendelian genetics. It not only allows us to precisely attribute a function to a gene but also brings us closer to defining its diagnostic and therapeutic potential for more common diseases such as cancer.”


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About A*STAR’s Institute of Molecular and Cell Biology (IMCB)

The Institute of Molecular and Cell Biology (IMCB) was launched on 23 January 1985, with its official opening ceremony held on 2 October 1987 at the National University of Singapore (NUS). It subsequently became an autonomous research institute (RI) of A*STAR, moving to Biopolis in 2004. IMCB’s vision is to be a premier cell and molecular biology institute which addresses the mechanistic basis of human diseases and its mission is to conduct cutting-edge discovery research in disease pathways; to groom early career researchers to be future leaders in research; and to collaborate with medical and industry communities for research impact. IMCB plays an important role training and recruiting scientific talents, and has contributed to the development of other research entities in Singapore. Its success in fostering a biomedical research culture in Singapore has catalysed Singapore’s transformation into an international hub for biomedical research, development and innovation.

Funded primarily by the Biomedical Research Council (BMRC) of A*STAR, IMCB’s Discovery research comprises 5 major programmes: Cancer Cell Signalling, Multi-Modal Molecular (M3) Biology, Epigenetics and Diseases, iPS cell and Regenerative Medicine, and Technology and Translation. IMCB’s technologies and platforms focus on Genome-wide RNAi, Humanized Mouse Models, Proteomics and Protein Engineering, Gene Therapy and Gene Editing, and Molecular Histopathology.

IMCB strives to maintain the scientific excellence of PI-driven research and at the same time aims to promote collaborative team-based projects of medical and industrial relevance.

For more information about IMCB, please visit www.imcb.a-star.edu.sg.

About A*STAR’s Institute of Medical Biology (IMB)

IMB is one of the Biomedical Sciences Institutes of the Agency for Science, Technology and Research (A*STAR). It was formed in 2007, with a mission to study mechanisms of human disease in order to discover new and effective therapeutic strategies for improved quality of life.

IMB has 20 research teams working in three primary focus areas - stem cells, genetic disease, and skin biology. The teams work closely with clinical collaborators as well as industry partners, to target the challenging interface between basic science and clinical medicine. IMB’s strategic research topics are targeted at translational research to understand the mechanisms of human disease so as to identify new strategies for disease amelioration, cure and eradication and to improve health and wellbeing. Since 2011, IMB has also hosted the inter-research institute Skin Biology Cluster platform, and leads major strategic funding programs in rare genetic diseases and in skin biology. In 2013 IMB became a founding institute of the Skin Research Institute of Singapore.

For more information about IMB, please visit www.imb.a-star.edu.sg.

About the Agency for Science, Technology and Research (A*STAR)

The Agency for Science, Technology and Research (A*STAR) is Singapore's lead public sector agency that spearheads economic oriented research to advance scientific discovery and develop innovative technology. Through open innovation, we collaborate with our partners in both the public and private sectors to benefit society.

As a Science and Technology Organisation, A*STAR bridges the gap between academia and industry. Our research creates economic growth and jobs for Singapore, and enhances lives by contributing to societal benefits such as improving outcomes in healthcare, urban living, and sustainability.

We play a key role in nurturing and developing a diversity of talent and leaders in our Agency and Research Institutes, the wider research community and industry. A*STAR oversees 18 biomedical sciences and physical sciences and engineering research entities primarily located in Biopolis and Fusionopolis.

For more information on A*STAR, please visit www.a-star.edu.sg.

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