Lisa Shaffer, PhD, FACMG - Chromosomes and Monosomy 1p36
Dr. Bernice Morrow - Genetic Research in Mice and associate of Dr. Shaffer's - speaker possibility in 2009
Signature Genomics, Dr. Shaffer’s company, is growing well and will have a research budget for further study even though her grants were denied. Families who would like to have a micro-array diagnosis can have that done through Dr. Shaffer’s research. It requires a blood draw but the information gained is worth it.
The history of the occurrence numbers: A study done on 60,000 newborns turned up 6 cases of 1p36 deletions which is where the 1 in 10,000 number came from. However, many diagnoses took multiple tests to arrive, so they estimated that perhaps only half of the cases are diagnosed. Which is where the estimate of 1 in 5,000 came from.
There are several variations of 1p36 deletions. .3, .2 are most common. Micro-Array testing allows you to see the exact size of the deletion. FISH testing isn’t as exact and the size of the deletion is much more difficult to determine.
Trisomy is more common than deletions. They are easier to diagnose and are the leading cause of mental retardation in newborns.
Structural rearrangements are where DNA has moved to somewhere else even though the total amount is correct. Some of these cause problems. Some do not.
Terminal Deletions are where the tip of the chromosome comes up missing. Interstitial Deletions are where there are two DNA breaks and material between them is missing.
Reciprocal Translocations are a rearrangement of the DNA pieces between different Chromosomes.
Micro-Array testing compares typical control DNA against the new sample and the test is run twice. It’s highly accurate and much faster than the older FISH tests which were hit and miss. This process is diagnosing many more chromosomal disorders in patients that were simply undiagnosed with FISH.
Micro-Array testing is also turning up more complex structure changes like small interstitial deletions in addition to terminal deletions.
197 cases of 1p rearrangements identified at Signature Genomics this year.
1994 to 2008 Research Project 150 families enrolled. Looking at specific structures and breakpoints. 33 different breakpoints were cloned and characterized.
Studies revealed that larger deletions occur in sperm versus eggs just due to lesser error checking or other unidentified causes.
There are no common breakpoint locations. Although terminal deletion breakpoints tend to cluster between 4 to 6 megabases.
Clinical features of 1p36 Deletions
Mental Retardation / Developmental Delays 100%
Large, late closing fontanels 97%
Cranioseynostosis 3% - early closing fontanels
Hearing Loss 82%
Heart Defects 43%
Growth Retardation 60%
Gastrointestinal troubles are now on the surveys that are sent out based on feedback from the support group.
There is NO correlation between deletion size and clinical features. Current thinking is that the majority of the important genes are at the very end of 1p.
Identifying the individual genes that contribute to features, there are ways to develop better treatments for those individual clinical features.
Talk to your doctor about the individual clinical features in order to make sure your child is receiving the care he or she needs in those areas.