Pre-Implantation Genetic Diagnosis for the Prevention of Genetic Diseases

Completion date: 01 January 2007 
The project focused on conducting mutation studies in a group of six autosomal recessive diseases. The results of the mutation study will be used to implement pre-implantation diagnosis and in-vitro fertilization with the study of an identified embryo free of the mutation. The diseases identified are either lethal and lack successful clinical management procedures or they may lead to irreversible neurological disabilities despite the management procedures used. The management of some of these diseases are very costly and require life-long intervention
This project was expanded into a diagnostic technical service provided to identified families. Currently, more than 100 subjects received that service

Principal Investigator
Ali Al- Odaib, PhD (Previously Dr. Ali Hellani) 

Serdar Coskun; Kamal Al-Jarudi; Pinar T. Ozand; Nadia Sakati; Aida Al Aqeel.

Research Outcome
The main goal of this project was to apply the PGD procedure to prevent the birth of children with genetic disorders in the Kingdom, which are either costly or very difficult to manage.   In this technique, embryos are generated by IVF and the diagnosis is usually made on cleavage stage embryos. This permits the transfer of only unaffected embryos thereby eliminating the need for abortion following the prenatal diagnosis in case of an affected fetus. The mutation analysis of selected genetic disorders were conducted and described.  In addition to the previously reported mutations, several novel mutations were identified in Nieman-Pick disease –B, Gaucher disease, and Canavan Disease.  All the enrolled families were referred to the IVF clinic at KFSH&RC to start the PGD procedure. 
Regardless of the significant advantages provided by PGD, there are still technical limitations regarding chromosomal abnormalities and single gene disorders.  Due to these limitations, there was a need for a technique that would be able to amplify the single cell DNA with high fidelity that suits microarray analysis or the diagnosis of any known single gene disorder by standard PCR technique.  Therefore, for the first time the multiple displacement amplification (MDA) was introduced to be the technique of choice in the amplification of very low DNA quantities in clinical samples in the PGD procedure. In this project MDA was used to amplify single cell DNA, which was then utilized in several PGD applications. The application of MDA may open new doors for two major PGD applications. Firstly, single cell karyotyping is becoming possible using the microarray comparative genome hybridization since this report showed a great success after a blind test an abnormality of chromosome 21. Secondly, single gene disorders would be easily diagnosed using mutation specific and STR PCR after MDA.
These results show the great potential and the capability to add more new diseases to the list of disorders that can be prevented in Saudi Arabia

Grantee Institution
King Faisal Specialist Hospital & Research Center


Publication list
"Multiple displacement amplification on single cell and possible PGD applications "Ali Hellani1,3, Serdar Coskun1, Moncef Benkhalifa2, Abelghani Tbakhi1, Nadia Sakati1, Ali Al-Odaib1 and Pinar Ozand , " "Preimplantation genetic diagnosis for Niemann-Pick disease type B" Ali Hellani, Edward H. Schuchman, Ali Al-Odaib, Aida Al Aqueel, Kamal Jaroudi, Pinar Ozand and Serdar Coskun (Prenat Diagn 2004; 24: 943-948)

Other Resources