Hair root FMRP expression for screening of fragile X full mutation females

Main Article Content

Lantip Rujito
Dwi Kustiani
Lies Anne Severijnen
Peter Hanzon
Sultana MH Faradz
Rob Willemsen


The fragile X syndrome is the most common form of inherited mental retardation in humans, caused by an expansion of the cytosine-guanine-guanine (CGG) repeat in the fragile X mental retardation 1 (FMR1) gene located on the X chromosome. Antibody tests have been developed to identify fragile X patients, based on the presence or absence of fragile mental retardation protein (FMRP) in both lymphocytes and hair roots. The objective of this study was to compare correlations of hair root and lymphocyte FMRP expression with cognitive functioning in female rural area probands carrying the full mutation. Thirty females (normal, premutation, or full mutation) were selected from Indonesian fragile X families and were tested for FMRP expression in lymphocytes and hair roots using the FMRP antibody test. Subject genotype was determined by Southern blot analysis, and IQ equivalent by Raven’s Standard Progressive Matrices. Statistical analysis was by Pearson correlation. FMRP expression in blood lymphocytes was relatively higher than that in hair roots, but hair root FMRP expression was strongly correlated with cognitive functioning in female full mutation carriers (r=0.64, p=0.015), whereas no significant correlation between lymphocyte FMRP and cognitive functioning was found (r=0.31, p= 0.281). Around 14% of subjects had a normal and 7% a borderline IQ level, while 79% had mild mental impairment. In conclusion, hair root FMRP expression may be a useful marker for identification of fragile X full mutation females.

Article Details

How to Cite
Rujito, L., Kustiani, D., Severijnen, L. A., Hanzon, P., Faradz, S. M., & Willemsen, R. (2011). Hair root FMRP expression for screening of fragile X full mutation females. Universa Medicina, 30(1), 11–21.
Review Article


ACOG Committee Opinion No. 469. Carrier screening for fragile X syndrome. Obstet Gynecol 2010;116:1008-10.

Hussein SM. Fragile X mental retardation and fragile X chromosome in the Indonesian population (dissertation). Sydney: Faculty of Medicine, University of New South Wales;1998.

Faradz SMH, Buckley M, Tang L, Liegh D, Holden JJA. Molecular screening for fragile X syndrome among Indonesian children with developmental disability. Am J Med Genet 1999; 83:350-1.

Faradz SMH, Gasem MH, Nillesen WM, Sistermans E, Hamel BCJ, Hagerman R. A high rate of fragile X in a small district of Indonesia can be traced back to one common ancestor. The 8th International Fragile X Conference; 2002 July 17-21; Chicago, USA.

Faradz SMH, Setyawati AN, Winarni T, Mundhofir FE, Nillesen WM, Zamhari M, et al. Molecular screening for fragile X syndrome in institutionalized mild mentally retarded individuals at BBFSBG Temanggung, Central Java (a preliminary study). The 12th International Workshop on Fragile X and X-linked Mental Retardation; 2005 August 26-29;Williamsburg, VA, USA.

Hagerman RJ, Hagerman PJ. Testing for fragile X gene mutations throughout the life span. JAMA 2008;300:2419-21.

Penagarikano O, Mulle JG, Warren ST. The pathophysiology of fragile X syndrome. Annu Rev Genomics Hum Genet 2007;8:109-29.

Luo XF, Zhong JM, Zhang XZ, Zou Y, Chen Y, Wu HP, et al. Hair root fragile X mental retardation protein assay for the diagnosis of fragile X syndrome. Chinese J Contemp Pediatr 2009;11:817-20.

Willemsen R, Mohkamsing S, De Vries B, Devys D, Van den Ouweland A, Mandel JL, et al. Rapid antibody test for fragile X syndrome. Lancet 1995;345:1147–8.

Willemsen R, Smits A, Severijnen LA, Jansen M, Jacobs A, De Bruyn E, et al. Predictive testing for cognitive functioning in female carriers of the fragile X syndrome using hair root analysis. J Med Genet 2003;40:377–9.

Raven J. The Raven’s progressive matrices: change and stability over culture and time. Cognit Psychol 2000;41:1-48.

The British Nutrition Foundation. The influence of diet on cognitive function, appetite and mood. Sainsbury, UK;2007.

Gunungkidul Regency, in cooperation with Regional Development and Poverty Reduction Program – RDPRP, Atlas Gunung Kidul regency, Final Main Report, March 2005. Available at: NESIA/Resources/Projects/288973-8033888998 /1218077-1150284192230/2654894-115028466 8244/Atlas.pdf. Accessed Mei 12, 2009.

Nell V. Cross-cultural neuropsychological assessment: theory and practice. London: Erlbaum;2000.

Barlow-Stewart K, Emery J, Metcalfe S. Genetic in family medicine: the Australian handbook for general practitioners. Canberra: Biotechnology Australia;2007.

Kenneson A, Zhang F, Hagedorn CH, Warren ST. Reduced FMRP and increased FMR1 transcription is proportionally associated with CGG repeat number in intermediate-length and premutation carriers. Hum Mol Genet 2001;10: 1449-54.

Zhou Y, Lum JMS, Yeo G-H, Kiing J, Tay SKH, Chong SS. Molecular diagnostics and genetics simplified molecular diagnosis of fragile X Syndrome by fluorescent methylation-specific PCR and gene scan analysis. Clin Chem 2006; 52:1492-500.

Janeway C, Travers P, Walport M, Shlomchik M, Immunobiolog. 5th ed. New York: Garland Science;2001.

Claycombe K, King LE , Fraker PJ. A role for leptin in sustaining lymphopoiesis and myelopoiesis. PNAS 2008;105:2017-21.

Rousseau F, Heitz D, Oberlé I, Mandel JL. Selection in blood cells from female carriers of the fragile X syndrome: inverse correlation between age and proportion of active X chromosomes carrying the full mutation. J Med Genet 1991;28:830–36.

Nossa GJV. The double helix and immunology. Nature 2003;421:440-4.