Identification of mutations in hereditary disorders of pediatrics
Informations
- Funding country
Hungary- Acronym
- -
- URL
- -
- Start date
- 2/1/2002
- End date
- 12/31/2005
- Budget
- 26,370 EUR
Fundings
| Name | Role | Start | End | Amount |
|---|---|---|---|---|
| Thematic Programme | Grant | 2/1/2002 | 12/31/2005 | 26,370 EUR |
Abstract
Recessively inherited syndromes are one of the most difficult problems encountered during clinical-genetics counseling sessions. Parents are usually healthy, while the frequency of affected individuals among offsprings is 25%. During our work we carry out molecular genetic screening and provide prenatal diagnosis whenever neccesary for patients with cystic fibrosis (CF) and congenital adrenal hyperplasia (CAH). These are classic monogenic autosomal recessive disorders that are quite common in our population and present with severe congenital defects. One of the most common inheritable causes of mental retardation is Fragile-X syndrome (Fra-X). The frequency in men 1:1250, while in women it is 1:2000. The severity of the disorder progresses in consecutive generations, due to a phenomenon called anticipation. The underlying pathology in most cases can be identified as a CGG triplet (FRAXA) amplification within the 27.3 region on the long arm of chromosome X. The identification of the FMR-1 gene allowed the diagnosis of the disease, on a molecular genetics level. Our proposed PCR-based method would provide a rapid and in expensive alternative for normal allele and premutation detection. We supplement this detection method with another screening procedure, based upon Southern-blotting technique which may reveal the complete nature of full mutations, including parts of the premutations themselves. Current modern DNA-diagnostic methods have been worked out for the analysis of mutations occuring in both types of inherited disorders. Our work may provide opportunity for the detection of unidentified mutations, with the help of exon amplification and direct DNA sequencing methods in family members with CAH and allow screening of an individual carrying a premutation (Fra-X). Our methods for both groups of disorders also permits the parallel initiation of prenatal screening tests. Thereupon offering families the opportunity to have healthy children, assisted by prophylactic treatment when neccesary (CAH) and to prevent the future birth of severely, mentally retarded children (Fra-X patients).