RELATIONSHIP BETWEEN FMRP EXPRESSION IN CELL FROM HAIR ROOTS AND BLOOD SMEARS WITH COGNITIVE FUNCTIONING IN FRAGILE X FULL MUTATION FEMALE

Abstract

Introduction: Fragile X syndrome is the most common form of inherited mental retardation in humans, caused by an expansion of the (CGG) repeat in the FMR1 gene located on X chromosome. Males carrying a full mutation are always mentally retarded, whereas females carrying a full mutation show mild to moderate mental impairment in only approximately 60% of cases, due to the X-inactivation process. The absence of the FMR1 gene product, FMRP, in the brain is hypothesized as causative for the observed mental retardation in fragile X patients. Antibody tests have been developed to identify fragile X patients, based on the presence or absence of FMRP in both lymphocytes and hair roots. It has been proposed that FMRP expression in hair roots from females carrying a full mutation may be used as a prognostic value for the mental capacities. Hair roots originate from the ectoderm, like brain tissue, and may therefore show a better correlation between FMRP expression and cognitive functioning than FMRP expression in lymphocytes, which originate from the mesoderm. Objectives: This study focussed on the relationship of the antibody test for cognitive functioning in females carrying a full mutation using either hair roots or bloodsmears. Method: Thirty samples from females carrying either a normal, premutation or full mutation were included in this study. All subjects were selected from an Indonesian fragile X family. The analyses were performed in a blind fashion. All subjects were tested for FMRP expression in lymphocytes and hair roots using the antibody test. Classification of the genotypes of the subjects was obtained by Southern blot analysis. IQ equivalent were determined using Standard Progressive Matrices (SPM) from Raven, a non-verbal IQ-test. Statistical analysis to show the correlation of FMRP expression and IQ equivalent was developed using Pearson correlation. Result: We report a significant relationship between FMRP expression in hair roots and cognitive functioning in female carriers of the fragile X full mutation (r=0.64, p=0.015) whereas in lymphocytes no significant relationship could be established (r=0.31, p= 0.281). We also reported that FMRP expression in blood smear was relatively higher than hair roots. We also demonstrated in our study group that IQ equivalents were about 14 % in normal range, 7 % in the borderline range and 79 % in mild mental impairment range. Conclusion: Although the size of our study group was limited the results suggest that FMRP expression in cell of hair roots has stronger correlation for cognitive functioning in females carrying a full mutation than FMRP expression in bloodsmears. Keywords: fragile X syndrome, females full mutation, FMRP, cognitive functioning