{'fraction_non_alphanumeric': 0.03965647890881536, 'fraction_numerical': 0.024501136650669362, 'mean_word_length': 5.111111111111111, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Molecular basis of mental retardation in a sample from Bulgaria.

Mental retardation in its syndromic and non-syndromic forms is highly heterogeneous in clinical and genetic point of view. Clinically, mental retardation and absent speech, which is the leading symptom in all cases may be the only finding in the patient, or appears in a combination with progressive neurodevelopmental deficits, seizures, autism, ataxia. Genetically, a number of genes, both X-linked and autosomal, have been indentified so far. We report the results from clinical examinations and molecular studies in a group of 67 Bulgarian mental retardation patients: 25 males with non-specific mental retardation, called Fragile X syndrome (FXS, OMIM #300624), 27 patients with a Rett syndrome-like phenotype (RTT, 0MIM#3 12750) (18 classical, 9 atypical), 9 with a Prader-Willi-like syndrome, 2 with Angelman syndrome (PWS/AS, OMIM#176270; 105830) and 4 patients with a microdeletion syndrome (MDS) phenotype - 2 with preliminary clinical diagnosis of Williams Beuren (WBS, OMIM#194050), 1 DiGeorge syndrome (DGS, OMIM#l 88400) and 1 Wolf-Hirschhorn syndrome (WHS, OMIM#194190). The degree of mental retardation was defined as: profound (IQ The research protocol was approved by The Ethics Committee for Research Investigations to the Medical University, Sofia, Bulgaria and informed consents were obtained from subjects' guardians. The genetic tests covered the genes FMRl by betaine-based-PCR (15), MECP2, CDKL5, ARX by sequencing analysis (1 , 2, 3, 6), and bisulfitetreated methylation-specific PCR analysis of exon 1 of the SNRPN (7). Multiplex ligation-dependent probe amplification (MLPA) analysis (10) was used to look for large deletions/duplications, to screen for microdeletion syndromes, and to clarify methylation status of FMRl and SNRPN genes. The MLPA analysis proved to be useful in confirming mosaic FXS cases (14), in detecting large deletions along the X-chromosome, in clarifying MDS, as well as in determining the type of mutation (deletion or uniparental disomy) in PWS/AS cases. FXS: The degree of mental retardation in this group was assessed as mild to moderate with two exceptions - one severe and one borderline case. The leading clinical symptom in the group of FXS boys was absent or delayed speech, intellectual impairment, and autistic behaviour sometimes in combination with hyperactivity and aggression. Physical delay was registered in 6 cases. Epilepsy or a single seizure was present in 4 boys. On the other hand, dysmorphic features were almost invariably found in the majority of cases. Parents frequently stated that the disease onset has been provoked by severe illnesses, like whooping cough, pneumonia, recurrent otitis. Sometimes, parents have noticed a regress of their child's development after an infectious disease. Karyotype analysis in all but one cases (46,fra(X)(q27.3)Y[18]/ 46,XY[22]) showed normal results. The analysis of FMRl gene showed full mutations in two patients and one mosaic case full mutation/ normal allele (14). The remaining 22 FXS boys with unclear molecular defect were subjected to additional genetic tests. Fifteen patients, including the four boys with epilepsy were screened for mutations in the ARX gene, and 7 were screened for mutations in the MECP2 gene. The reasons for this testing are the results of some studies, where ARX gene mutations have been found to be associated with mental retardation and epilepsy (9, 13). Mutations in the MECP2 gene have been published to cause moderate mental retardation and obesity, clinical features overlapping with a PWS phenotype (8). In our study of mentally retarded boys, mutations were detected neither in the ARX gene nor in the MECP2 gene. In 4 cases the concomitant diagnosis of a PWS/AS was checked by genetic tests and the diagnosis was not confirmed. One patient was analyzed also by the microdeletion MLPA kit, but no pathological changes were detected. …