Evaluation of clinical checklists for fragile X syndrome screening in Brazilian intellectually disabled males: proposal for a new screening tool.

Patients with fragile X syndrome present a variable phenotype, which contributes to the underdiagnosing of this condition. The use of clinical checklists in individuals with intellectual disability can help in selecting patients to be given priority in the molecular investigation of the fragile X mutation in the FMR1 gene. Some features included in checklists are better predictors than others, but they can vary among different populations and with patient age. In the present study, we evaluated 20 features listed in four clinical checklists from the literature, using a sample of 192 Brazilian male patients presenting with intellectual disability (30 positive and 162 negative for fragile X mutation). After statistical analysis, 12 out of the 20 items analyzed showed significant differences in their distributions between the two groups. These features were grouped in a new checklist that can help clinicians in their referral for fragile X testing in patients with developmental delay.

Pure duplication 1q41-qter: further delineation of trisomy 1q syndromes.

Several authors have attempted to characterize the partial 1q trisomy syndrome, reporting clinical features such as mental retardation, macrocephaly, large fontanels, prominent forehead, broad flat nasal bridge, high-arched palate, micro/retrognathia, low-set ears, and cardiac defects. However, defining the partial trisomy 1q syndrome is difficult, because it is a rare chromosomal abnormality and in most instances the trisomy 1q is combined with partial monosomy of another autosomal segment. We report on the clinical and molecular cytogenetic study of a patient who presents pure partial 1q duplication. This is the first case of pure duplication 1q41-qter in the literature.

Clinical checklists in the selection of mentally retarded males for molecular screening of fragile X syndrome

Fragile X syndrome is the most frequent cause of inherited mental retardation. The phenotype in this syndrome is quite variable and less conspicuous in younger patients, making clinical diagnosis difficult and thus making molecular diagnosis necessary. The use of clinical checklists in mentally retarded individuals can help selecting patients to be given priority in the molecular investigation for the fragile-X mutation in the FMR1 gene. We evaluated two clinical checklists in a sample of 200 Brazilian male patients with mental retardation. The highest scores in the two checklists concentrated among the 19 males (9.5 percent) found to carry full mutations. Our results confirm the importance of fragile-X checklists as a clinical tool in the study of mentally retarded patients.

Breakpoint mapping in a case of mosaicism with partial monosomy 9p23 --> pter and partial trisomy 1q41 --> qter suggests neo-telomere formation in stabilizing the deleted chromosome.

We report on a clinical and molecular cytogenetic study of a patient who presents a complex chromosomal rearrangement with two different cell lines. Using high-resolution GTG banding and fluorescence in situ hybridization (FISH) with several probes, including bacterial artificial chromosomes (BACs), the karyotype was defined as 46,XX,del(9)(p23)[54]/46,XX,der(9)t(1;9)(q41;p23)[46], indicating the presence of monosomy 9p23 in all cells and trisomy 1q41 in approximately 50% of the cells. The patient studied presents most of the manifestations of the 9p deletion and 1q duplication syndromes. The breakpoint was mapped at 9p23 with a loss of approximately 13.9-Mb of DNA. The duplicated segment consists of approximately 35 Mb from 1q41-qter region. We also suggest that a mechanism for telomere capture and interstitial telomeric sequences (ITs) is involved in a neo-telomere formation in one of the cell lines. This study highlights the importance of combining high-resolution chromosome and FISH with BACs in order to make genotype-phenotype correlations and to understand the mechanisms involved chromosomal aberrations.