Three individuals (2.6%) with the FRAXA form of the fragile X syndrome and one boy (0.9%) with FRAXE mental retardation were detected; a total of four newly diagnosed fragile X families were identified.
FRAXA coincides with a >200 CGG*CCG repeat tract in the 5' UTR of the FMR1 gene, and alleles prone to fragility are associated with Fragile X (FX) syndrome, one of the leading genetic causes of intellectual disability.
Fragile X syndrome linked to the FRAXA locus is the most common inherited genetic disease accounting for mental retardation and is usually caused by the expansion of an unstable CGG repeat in the first exon of the FMR1 gene on the X chromosome.
In view of these data, we screened MECP2 in a cohort of 185 patients found negative for the expansions across the FRAXA CGG repeat and reported the identification of mutations in four sporadic cases of MR. One of the mutations, A140V, which we found in two patients, has been described previously, whereas the two others, P399L and R453Q, are novel mutations.
At least seven disorders result from trinucleotide repeat expansion: X-linked spinal and bulbar muscular atrophy (SBMA), two fragile X syndromes of mental retardation (FRAXA and FRAXE), myotonic dystrophy, Huntington's disease, spinocerebellar ataxia type 1 (SCA1), and dentatorubral-pallidoluysian atrophy (DRPLA).
We have investigated a population consisted of 276 males with idiopathic mental retardation or learning disability and a control sample of 207 non-affected boys in order to determine if there was a possible phenotype consequence of the expanded unmethylated alleles for FRAXA/FRAXE loci.
Neuroanatomical differences between two monozygotic twins with an FMR-1 mutation who are discordant for mental retardation are localized to the cerebellum, lateral ventricles and subcortical nuclei.
The recent observation that the mutation underlying a number of genetic diseases including fragile sites, FRAXA and FRAXE (associated with mental retardation), myotonic dystrophy, spinal and bulbar muscular atrophy (Kennedy's disease), Huntington's disease and spinocerebellar ataxia type 1 are caused by the expansion of a trinucleotide repeat sequence will lead to interest in the identification of such sequences in regions related to other diseases.
The aim of this population screening study was to determine if Fra-X or FRAXE mutations are the cause of a number of cases of mental retardation in a sample of Mexican children with mental retardation of unknown cause (MRUC) and to stress the importance of performing molecular analysis of the FMR-1 gene in all patients with MRUC.
Fragile X syndrome, the second most common genetic cause of mental retardation, is due to the expansion of a trinucleotide repeat (CGG)n within the first exon of the FMR-1 gene.
The purpose of the study was to estimate the frequency of FRAXA mutation in individuals with nonspecific mental retardation without family history and phenotypic stigmata in the Hellenic population.
In a second series, we screened 140 patients with MR and behaviour disturbance who did not fulfil the de Vries criteria for subtelomeric rearrangements and who had a normal karyotype and no detectable FRAXA mutation.
To date, seven diseases have been identified as expanded repeat disorders: the fragile X syndrome of mental retardation both FRAXA and FRAXE loci), myotonic dystrophy, X-linked spinal and bulbar muscular atrophy, Huntington's disease, spinocerebellar ataxia type I, dentatorubral-pallidoluysian atrophy, and Machado-Joseph disease.
Determination of the CGG repeat number was achieved by polymerase chain reaction (PCR) on modified DNA from 129 unrelated Mexican mestizos (46 FRAXA-negative males with mental retardation and 83 healthy individuals).
This dinucleotide repeat could be useful in determining the parental origin of a new fra (X) mutations and evaluating the role of FMR-1 in X-linked non-specific mental retardation.
Expansion of a (CCG)n repeat in the FMR2 gene corresponds to the FRAXE fragile site which lies distal to FRAXA and is also associated with mental retardation, but it is less frequent and lacks a consistent phenotype.
We have analysed the size of the non-expanded FRAXA CGG repeat in 385 male patients affected by mental retardation and in 182 unrelated normal chromosomes as control.
Multiplex XLMR pedigrees have been reported with only one mutated patient having autism and MR: different X-located MR genes have been shown to be involved (NLGN4, MECP2, OPHN1, ZNF674 and FRAXA) which does not suggest that they could be "autism genes".