Direct diagnosis of the mutation that causes fragile X chromosome syndrome. Experience in Costa Rica.
DOI:
https://doi.org/10.51481/amc.v44i1.396Keywords:
diagnóstico molecular, FRAXA, cromosoma X, , retardo mental hereditario, FMR1, mutaciones inestables., genética humanaAbstract
Fragile X syndrome is the most common here-ditary type of mental retardation, affecting 1:4000 males and 1:6 000 females. Unfortunately,most persons with this syndrome have not beendiagnosed and are classified as cases of mentalretardation of unknown origin. The correct etio-logical classification of these patients wouldallow their families to avoid recurrence of thisdisease through adequate genetic counseling.As a result, this study intended to provide accu-rate molecular diagnosis of fragile X syndromein mentally retarded patients with clinical or cy-togenetic suspicion of the disease, to detect thenormal transmitting males and female carriersin each of the proband' s families and to promo-te prevention after proper genetic counseling.To achieve this, genomic DNA was digestedwith Hind III, EcoRI and EagI and Southernblotting was performed with probes Ox1.9 andStB12.3. To asses the size of the trinucleotiderepeat, PCR was used in some of the cases.Three groups were studied: group one with 13children with the cytogenetic marker, 30 oftheir close relatives conformed group two andgroup three with 15 clinically suspicious fragi-le X syndrome children. Results:of the 13 pro-bands, four proved not to be fragile X cases sin-ce their average repeat number was 30. In grouptwo, two females with the full mutation, one normal transmit-ting male and eleven female carriers with the premutationwere found. In group three an additional female with the fullmutation was identified, the rest had normal DNA and cyto-genetic test results. In summary, DNA studies are a betterway to accurately asses the full mutation and premutation ca-rriers. The right diagnosis renders benefits to fragile X casesin terms of the interventions they need and to carriers sincethis information is a must for proper genetic counseling andprevention. Moreover, molecular studies are cheaper than cy-togenetic diagnosis in well equipped laboratories with trainedpersonnel.
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