Down Syndrome Research

By Dr. Ananya Mandal, MDReviewed by Sally Robertson, B.Sc.

Down syndrome or Down’s syndrome is a genetic condition caused by the presence of an additional copy of chromosome 21 in a person’s cells. This additional DNA causes the physical characteristics and developmental problems associated with the syndrome.

The extra copy of chromosome 21 (also referred to as trisomy 21) is acquired by chance and although Down’s syndrome is more common among babies born to mothers of an older age, mothers of any age may have a baby with the condition.

Down’s syndrome affects hundreds of babies worldwide irrespective of race, ethnicity, maternal age at conception, and social or economic class. Much research has been carried out to determine exactly how the extra chromosome 21 causes symptoms of the condition.

Research focused on the genes expressed in Down’s syndrome has led to the identification of a particular region of chromosome 21 that contains the main genes involved in the pathology of this condition. The approximate location of this region is 21q22.3 and much of the research carried out to search for key genes in Down’s syndrome involves the region 21q21–21q22.3.

Research conducted by J.R Arron et al has shown that dysregulation of transcription factors may be related to the phenotypes associated with Down’s syndrome. One of these transciption factors, NFAT, is controlled by two proteins, Down’s syndrome critical region 1 (DSCR1) and dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A).

The DSCR1 and DYRK1A genes are located on chromosome 21 and give rise to 1.5 times the usual amount of these proteins that is found in healthy cells. The high concentration of these proteins keeps NFAT mainly located in the cytoplasm rather than in the nucleus, which means NFAT is prevented from activating the transcription of certain genes. The proteins that these genes code for are therefore not produced.

Studies simulating human trisomy 21 in murine models have suggested that this dysregulation of transcription factors causes a weakened grip strength similar to the poor muscle tone observed in people with Down’s syndrome. Studies are currently ongoing to locate further genes in the Down’s syndrome critical region that may contribute to the pathology of the condition.

Further Reading

• All Down Syndrome Content
• Down Syndrome - What is Down Syndrome?
• Down Syndrome Symptoms
• Down Syndrome Complications
• Down Syndrome Screening