Disclaimer: This book was created after the 1998 Family Conference.  The articles are important to all of those involved with RTS.  This is online without permission from Dr. Rubinstein and the Cincinnatti Rubinstein-Taybi organization.  They would prefer that you call Dr. Rubinstein at  1-800-344-2462 ext. 4621 and request a copy of the book.  I would encourage everyone, especially those with a child who has RTS to call the above number and request a copy of this book.  I have been reassured by Mark Shannon that this book will be sent to anyone who requests it, regardless of country.
All the information from the book is not online (another reason to call and request the book).  Left out are articles which are copyrighted or are not appropriate for the web site (includes list of attendees).  All articles which are deemed “public domain” are included..
Diane Wardlow

Chromosome 16 Microdeletions in Rubinstein-Taybi
Syndrome Assessed by Fluorescence in Situ Hybridization
(FISH) Using Five Cosmids Spanning the CBP Gene

Ruthann I Blough¹, Fred Petrij², Johannes G. Dauwerse², Lester Weiss³, Paula Czarneck³, Jack H. Rubinstein¹, Howard M. Saal¹ 

¹The Children’s Hospital Medical Center (CHMC), Cincinnati OH, ²Department of Human Genetics, Leiden University, The Netherlands, ³Henry Ford Hospital, Detroit, MI

The Rubinstein-Taybi syndrome (RTS) is a rare condition characterized by broad thumbs and broad big toes, facial dysmorphism, and mental retardation.  FISH using probes specific to chromosomes 16p13.3 identified microdeletions in 20-25% of initially reported cases.  Later studies, however, have suggested a somewhat lower rate of microdeletions.  The disrupted gene has been identified as coding for the CREB-binding protein (CBP).  In the majority of cases studied by FISH the prove used was specific to the 3’ region of the CBP gene.  In cases studied with additional probes, individuals with deletions detected by FISH appear to be deleted for the 3’ ends as well as the entire CBP gene.

We have performed FISH on a series of 70 patients with an established diagnosis of RTS, using a panel of 5 cosmids which span the CBP gene.  The initial 43 samples were collected during the 1993 International Family Conference on Rubinstein-Taybi Syndrome in Cincinnati, OH.  Each of these individuals was examined by the same team of physicians and had a clinically confirmed diagnosis of RTS.  An additional 27 samples were collected after the conference from a wide variety of referring institutions.  Of 70 individuals examined, 64 had no detectable deletion.  This represents a lower than expected rate of deletion by FISH based on the widely quoted rate of 20-25%.  Six patients demonstrated complete or partial deletion of the CBP gene (Figure 1, below.) The finding of two paretial, 5’ deletions and an interstitial deletion of the 3’ region of the CBP gene among these individuals adds to the known spectrum of mutations of this gene in RTS.

These studies demonstrate the need for evaluation of the entire CBP gene region for deletions in RTS patients rather than only the 3’ region, since 3 of 6 deletions would have missed if only the 3’ FISH probe were used. Further, this study supports more recent reports that the true rate of microdeletion across the CBP gene detectable by FISH is ~10% of confirmed cases of RTS, FISH is a poor diagnostic test.  A deletion-positive study can be confirmatory, but a deletion-negative study cannot rule out a diagnosis of RTS. Different approaches to the clinical laboratory diagnosis of RTS continue to be explored at CHMC Cincinnati.

Replication:
This information is in the public domain unless otherwise indicated.  Readers are encouraged to copy and share it, but please credit The Proceedings for the 1998 International Family Conference on Rubinstein-Taybi Syndrome.

Funding:
UACCDD receives major support from the Hamilton County Mental Retardation Service Levy.  Additional funding sources include: United Way and Community Chest; Maternal and Child Health Bureau and the Administration on Developmental Disabilities of the Department of Health and Human Services; other county, state, and federal agencies; foundations; and individual contributions.
The 1998 International Family Conference on Rubinstein-Taybi Syndrome is very grateful for the generous support of The Special Friends Foundation.

This document was added to the Rubinstein-Taybi web site in November 2000.

If any of the information found on this website does not adhere to copyright laws it is unintentional, please contact dwardlow@uswest.net and it will be removed from the site.

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