13th balkan biochemical biophysical days & meeting on metabolic disorders’ programme & abstracts

NOVEL APPROACHES TO GENETIC DISEASES

Pinar T. Ozand MD,Ph. D., Chairman,

Department of Genetics, King Faisa Specialist
Hospital & Research Centre. PO Box 3354, Riyadh 11211, Saudi Arabia.

The  objective  of  this  presentation  is to present the novel  strategies  adopted to prevent genetic diseases in Saudi   Arabia.   The  genetic  diseases  either  due  to chromosome  defects  or  to  alterations  in  single gene structure  produce  infants with usually severe diseases.

The  management  of such disorders is: (A) usually costly due  to the fact the morbidity lasts for many years,  (B) not  always  successful  and  doesn’t always produce good results  and  (C)  disrupts  the  normal family function. These  diseases, particularly those inherited single gene disorders  plague  the  communities  with  consanguineous marriages.  Based  on  our  experience in the Kingdom, we have  adopted  several  strategies  to combat this public health  problem.  The  methods to combat genetic diseases include:   (1)  if  nothing else is possible to perform a neonatal  screening  program for treatable diseases. This must   be   done   within   2-3  days  after  birth.  (2) Preimplantation  diagnosis.  Initially we have focused on six  major  single  gene  diseases  of the country: MSUD, biopterin   dependent   PKU,   homocystinuria,  propionic acidemia, Niemann Pick disease type B and Gaucher disease type  A.  All  of  these diseases are either difficult to manage  requiring  the devotion of many clinical hours by the  physician  or  their procedures of management or are extremely  costly. (3) Premarital screening. Applying the mutations on a DNA chip and screening the extended family as well as population for carriers of these diseases. (4) Chromosome  abnormalities  to be studied by CGS (complete human  genome screening) that can be applied to a newborn as  well as in preimplantation efforts. This presentation will detail these approaches and our preliminary results.

The   result  with  preimplantation  intervention  in  an ataxia-telangiectasia family will be presented.

Aleksandar J DIMOVSKI^1,2, Dijana Plaseska-Karanfilska ¹⁾, Ana-Marija STEFANOVSKA¹,

Colorectal cancer (CRC) is one of the most common cancers and the second cause of death in developed countries. In addition to environmental factors, genetic predisposition has a significant role in the ethiopathogenesis of the disease. Apart from the two dominantly inherited syndromes (FAP and HNPCC) several low penetrance genes were implicated in the initiation of colorectal cancerogenesis. The aim of this study was to determine the molecular basis of FAP, the incidence of HNPCC and the frequency of polymorphisms in several low penetrance genes (I1307K and E1317Q in the APC gene, TRI(6A) and CCND1) associated with CRC. A total of 173 patients with CRC, of which six patients with multiple adenomatous polyposis, and a control group of 100 newborns and 100 aged individuals were included in this study. Out data indicate that FAP and HNPCC have relatively low frequency of 0.1% and <5%, respectively, in our population. Deletions of APC gene are relatively frequent in our patients with FAP. Also, we suggest that aberrant splicing of this gene is a probable mechanism in etiopathogenesis of the multiple adenomatous polyposis phenotype. Microsatellite instability was present in 13.4% of patients and was associated with absence of nodal infiltration, proximal localization, Dukes' A and B stage and mucionous histotype. No I1307K and E1317Q polymorphisms in the APC gene were detected among our patients. The frequency of the TRI(6A) polymorphism was identical among patients and controls thus excluding this variant as a tumor susceptibility allele in our population. A statistically significant difference in the frequency of the CCND1 polymorphism was found in the group of patients less than 60 years of age with MSI tumors, indicating that CCND1 polymorphism may influence the age at onset of colorectal cancer in young patients only when their tumors exhibit an MSI phenotype.