Resumo

CUENCA-BERGER, Patricia; MORALES-MONTERO, Fernando  e  CASTRO-VOLIO, Isabel. Diagnóstico directo de la mutación que causa el síndrome del cromosoma X frágil: experiencia en Costa Rica. Acta méd. costarric [online]. 2002, vol.44, n.1, pp.27-33. ISSN 0001-6002.

Fragile X syndrome is the most common hereditary type of mental retardation, affecting 1:4 000 males and 1:6 000 females. Unfortunately, most persons with this syndrome have not bcen diagnosed and are classified as cases of mental retardation of unknown origin. The correct etiological classification of these patients would allow their families lo avoid recurrence of this disease through adequate genetic counseling. As a result, this study intended to provide accurate molecular diagnosis of fragile X syndrome in mentally retarded patients with clinical or cytogenetic suspicion of the disease, to detect the normal transmitting males and female carriers in each of the proband's families and to promote prevention after proper genetic counseling. To achieve this, genomic DNA was digested with Hind 111, EcoRI and Eagl and Southern blotting was performed with probes Oxl.9 and StB 12.3. To asses the size of the trinucleotide repeat, PCR was used in some of the cases. Three groups were studied: group one with 13 children with the cytogenetic marker, 30 of their close relativas conformes group two and group three with 15 clinically suspicious fragile X syndrome children. Results: of the 13 probands, four proved not to be fragile X cases since their average repeat number was 30. In group two, two females with the full mutation, one normal transmitting male and eleven female carriers with the premutation were found. In group three an additional female with the full mutation was identified, the rest had normal DNA and cytogenetic test results. In summary, DNA studies are a better way to accurately asses the full mutation and premutation carriers. The right diagnosis renders benefits to fragile X cases in terms of the interventions they need and to carriers since this information is a must for proper genetic counseling and prevention. Moreover, molecular studies are cheaper than cytogenetie diagnosis in well equipped laboratories with trained personnel.

Palavras-chave : genética humana; diagnóstico molecular; FRAXA; cromosoma X; retardo mental hereditario; FMRI; mutaciones inestables.