Conference Report: Monosomy 1p36

Dr. Shaffer's second lecture at the conference was titled simply, Monosomy 1p36.  She spoke for over and hour and I typed as fast as I could.  Here is what I was able to put down:

FISH probes can find out if the ends of the chromosome is in place over two or three years.  MicroArray testing can do the same work in two to three days.

About 50% of 1p36 deletions are missed in cytogenetic analyses.  MicroArray testing needs to get out into clinical testing, not just in research labs anymore.

Interstitial deletions aren’t really rare.  They just get missed by the FISH tests.  They are showing to be more frequent in MicroArray testing.

Efforts are being made to map the genes in the 1p36 area by looking at deletion specifics and the symptoms the patients present.

The body may have chromosomal repair mechanisms that place pieces at the end, sometimes these are the wrong pieces.  This results in telomere rearrangement.

Monosomy 1p36 Research Project

141 families enrolled in the study

Began at Baylor in 1994

Goals

Map deletions

uncover complex arrangements

4 to 5 million base pairs is the average size of deletions.  Egg deletions are usually smaller and sperm deletions are usually larger.  The check mechanism is less stringent in sperm production than in egg production.  This is still being studied

There seems to be a particular genetic sequence that  is more prone to breaking.  Called translin

Genes interact with each other in complex ways so symptoms are not cut and dried and in terms of what symptoms are linked to what deletion.

Clincal symptoms

100% have mental retardation and 

97%  late closing fontanels

3% early closing fontanels

82% Hearing loss - Improving hearing over time

60% Growth Retardation

48% Epilepsy

43% Congenital Heart Defects

17% Cleft abnormalities

78% Hypotonia

64% Speech delays

64% Seizures

42% Feeding Difficulties

~40% Poor swallowing function

Data on hearing loss is confusing because different types are diagnosed and hearing seems to improve with time.

Gastrointestinal issues - haven’t been studied a lot but constipation and other issues do appear to be linked.

The study is getting close to determining which genes control cardiomyopathy.  If a child has this they are encouraged to enroll in the study to provide more data to help get an answer.

There appear to be two regions that affect seizures.  One region has a link to limited seizures that go away.  Another region is linked to chronic seizures.

There are also two regions associated with hearing loss.

There is not a direct correlation between deletion size and clinical features.  Most of the active genes are near the end and many interact with other chromosomes

Epigenetics - the study of other effects that contribute to expressing of certain genes. Such as DNA folding - the way the DNA folds up into chromosomes

Gene therapy currently only works well at putting information back into a certain organ that is missing information to make a certain enzyme.

It is unknown whether speech delay is a result of the mental delays or a direct result of a missing genetic material.

Dr. Shaffer mentioned that she would make her slides available to the group later on, so when I track those down I'll post them here as well.  

Coming up:  A few insights from the other speakers, pictures of the conference and some fun personal experiences meeting other families.