Genetics Update - Lisa Shaffer PhD

Thanks to the families who have participated in the studies. 157 participants so far. About a half of a percent of all births have a chromosomal abnormality. 1 in 5000 births is a 1p36 Deletion. The end of the first chromosome is difficult to see. Microscopes simply cannot see in enough detail to make a 1p36 diagnosis.

Microarray testing is making much more reliable results available. Microarray testing allows for a comparison of control DNA and the patients DNA and any differences like a deletion or translocation are immediately apparent.

There is an increased risk of other 1p36 Deletions in future children even if neither parent has a balanced translocation. The cell creating the eggs or sperm are missing that information on 1p. There are clinics that can perform genetic analysis of the eggs and sperm during fertilization. The risk of subsequent children being born with a 1p36 deletion is about 1%. This is higher than the risk in the general population.

Although it's rare the cell responsible for the production of 1p deleted sex cells must be there because the deleted regions are identical in the siblings. Blood testing to be a part of Dr. Shaffer's study can be sent to her. Going to Spokane isn't required. The families have to contact Dr Shaffer. Because of privacy laws, Dr Shaffer can't contact the families when a positive diagnosis is made at her lab.

Deletion sizes are very different and distinct between patients. The average size of the deletion is 2 to 2.5 megabases. Often the break point is 2 megabases in on the chromosome. Deletion size doesn't seem to correlate to the symptoms or severity of the child's health difficulties.

In the study, about 50% have terminal deletions, 33% have interstitial deletions and the rest are complex rearrangements. The most common breakpoint is at 1p36.33. But there are many others in the surrounding area.

Dr Shaffer is now working to identify the genes that cause the clinical features. This will aid in identifying targets for treatment. Catching the symptoms and treatments early is very helpful. KCNAB2 - may contribute to seizure activity. MMP23 may contribute to the large late closing fontanelles. SKI - implicated in clefting abnormalities. Tracking cases with smaller deletions allows the study to tie the genes to the clinical features. Comparing genotypes of different cases and their clinical cases is assisting in identifying the individual genes that are associated with different symptoms.

Josh Milner is putting together a study about allergies and and associated genes. He's like contact from individuals in our group who have allergies, old sores, thin skin, heart abnormalities, etc. He can be reached at jdmilner@niaid.nih.gov.

Know your rights regarding sharing your medical information. If you are contacted by a researcher, make sure they are working with their Institutional Review Board (IRB). Each university has one to determine ethics and protection of patient's personal data. Do not participate in non-IRB approved studies. Don't participate in studies that you are not comfortable with. Know your rights and don't be pushed around. Ask about purposes, risks, processes, costs, etc.