Fragile X syndrome (FXS,MIM # 309550), the most common inherited form of mental retardation, is due to a unique mutation that leads to the silencing of the FMR1gene. It has an estimated frequency of 1/4000 men and 1/8000 women. The mutation is due to an expansion of an unstable CGG repeat sequence located in the 5' untranslated region of the FMR1gene. The full mutation (FM) consists of over 200 repeats and is abnormally hypermethylated. As a consequence, no mRNA is produced and the lack of the gene product, FMRP, an RNA-binding protein, is responsible for the clinical picture of the disease (1, 2). The FMR1gene in its normal state produces a protein that is thought to play a key role in both pre- and postnatal brain development. Fragile X mental retardation protein (FMRP) is expressed in a variety of tissues, but it is most abundant in neurons. The fragile X premutation alleles (PM) are defined by a CGG expansion within the range of approximately 55-200 repeats, and generate some protein. Premutations are unstably transmitted from mother to child and associated with a significant risk of further expansion to a full mutation during oogenesis and postzygotic mitosis in succeeding generations. The prevalence of the FMR1premutation in the general population is relatively high, occurring in an estimated 1 per 813 men and 1 per 259 women (2). The clinical consequence of the expanded CGG repeat in the FMR1gene was thought to be restricted to those with full mutation. The behavioural phenotype of FXS includes hyperarousal, social anxiety and withdrawal, social deficits with peers, abnormalities in communication, unusual responses to sensory stimuli, stereotypic behaviour, gaze aversion, autism spectrum disorders, inattention, impulsivity, and hyperactivity (1, 2). The phenotype in females with fragile X is usually less distinct than in males. Cognitive defects and behavioural problems, such as shyness, attention problems, and anxiety, are less conspicuous than in affected males. There is also evidence that differences in CGG trinucleotide repeat sizes within premutation ranges may affect clinical involvement (2). However, the unmethylated long CGG tract in premutation carriers has been associated with specific phenotypes unrelated to FXS. 20-25% of carriers of PM have prominent ears, flexible finger joints, mild learning disabilities, and emotional problems such as mood lability, anxiety and social phobia. Shyness often associated with poor eye contact is a common complaint of females with the premutation and was observed in 36% of women with the premutation compared to 18% of controls (3, 4).

The aim of our study was to assess the influence of raising mentally retarded children with FXS on the mother's psychological status.

The study was conducted at the Department of General, Molecular Biology and Genetics, Medical University of Silesia in Katowice, from February to May 2008. Study participants were informed of the purpose of the study and all provided their informed consent. The procedures were conducted in accordance with Institutional Guidelines and Regulations and with the Guidelines for the Conduct of Research Involving Human Subjects approved by the appropriate institutional review board (IRB) Bioethical Committee of the Medical University of Silesia in Katowice, PL, No. L.dz. KNW-6501-185/07/08. The study included 15 mothers of children diagnosed with FXS. They were Caucasians/white. The group as a whole ranged in age from 28 to 48 years (M= 40.2, SD=5), with an average of 11.21 years of education (range 8-12, SD=1.05). The participants were asked to complete a questionnaire regarding topics such as personal and family history of mental illness, medication use, and demographic information, and were referred for psychological evaluation consisting of clinical review followed by psychological testing. The tests were administered in the following order: BDI, HAM-D and MMPI. BDI and HAM-D were used to rate the severity of a patient's depression (5, 6). MMPI is a 567-item true/false inventory used to evaluate the thoughts, emotions, attitudes, and behavioural traits that comprise personality. The results of the MMPI test reflect an adolescent's personality strengths and weaknesses, and may identify certain disturbances of personality (psychopathologies) or mental deficits caused by neurological problems. There are validity scales L, F, and K that suggest whether the patient responded to the test items in a manner that would produce valid results. The remaining scales are the clinical scales, numbered 1-9 and 0, originally labelled: Hy (hypochondria), D (depression), Hs (hysteria), Pd (psychopathic deviation), Mf (masculinity-femininity), Pa (paranoia), Pt (psychasthenia), Sc (schizophrenia), Ma (hypomania), Si (social introversion), designed to measure common types of psychopathology. There are also subscales of the clinical scales developed by Harris et al., which have come to be widely used. Statistical analyses were performed using Kruskal-Wallis test. We chose a value of p<0.0001 as the level of statistical significance. Spearman test was used to compare results obtained in BDI, HAM-D scales and clinical, Harris-Lingoes MMPI scales.

Results obtained in BDI and HAM-D were within the normal results and did not show any depressive symptoms. The results obtained in control MMPI scales showed significantly higher values of the Infrequency-Psychopathology (Fp) scale, with the mean result 76.2 T (tab. 1). The results obtained in clinical MMPI scales were within the normal range. Clinical subscales, so-called Harris-Lingoes scales, showed higher values for Hy4 (somatic complaints) subscales, with the mean score 69.27 (tab. 2). The analysis of results obtained in BDI and HAM-D scales and control, clinical and Harris-Lingoes MMPI scales showed an existing correlation. Results obtained in the BDI scale showed a statistically significant positive correlation with the results of the Pt (psychasthenia) scale and negative with the results in the Ma (hypomania) scale (tab. 3). There was a statistically significant positive correlation between BDI scale and Harris-Lingoes subscales in D1, D4, D5 and Sc3. There was also a positive correlation between HAM-D scale and Harris-Lingoes subscales in D1 and Hy3 (tab. 4). In mothers of children with FXS we could observe tension, anxiety and phobic behaviour. They may feel guilty.