Rett syndrome from quintuple and triple deletions within the MECP2 deletion hotspot region

Rett syndrome results from mutations in the X-linked methyl-CpG-binding protein 2 (MECP2) gene, which are nearly always lethal in males and lead to regression and reduced life expectancy in females. Herein we report one propositus with five tandem deletions and a second propositus with three tandem deletions within MECP2 exon 4 that encode truncated protein products resulting in classic Rett syndrome. These deletion breakpoints and single deletions in 3 other patients were all found within a 185-bp region along with 64 of 69 other reported deletion breakpoints in the MECP2 gene. Illegitimate recombination resulting in deletion at a substantial proportion of the shared MECP2 sites is enhanced by repeated guanosine (G) DNA sequences in the antisense direction, consistent with reports at other gene loci that polypurine (multiple guanosine or adenosine (A)) basepairs enhance sequence deletion. Multiple deletions at the same poly G recombination sites confirm the existence of deletion hotspots in this gene region with numerous repeated antisense sites that are enriched 26- to 161-fold. Deletion by illegitimate recombination within a single allele can occur during mitotic or meiotic cell cycles. Although prone to disease-causing deletion, this region is unique in humans and highly conserved among mammals for the last 75 000 000 years to maintain the MECP2 gene's critical function.     

Prevalence and risk indicators of oral mucosal lesions in an urban population from South Brazil

Oral Diseases (2011) 17 , 171–179 Objective: The objective of the study was to assess the prevalence of oral mucosal lesions (OML) and to perform a multivariable risk assessment of demographic, socioeconomic, behavioral, and oral risk indicators for its occurrence in an urban population in South Brazil. Methods: This cross‐sectional study selected 1586 subjects (719M/867F, age: 14–104 years) using a multistage probability sampling strategy (65.1% response rate). Prevalence, odds ratios (OR), and confidence intervals (95% CI) were calculated accounting for the survey design. Results: Leukoplakia and lichen planus were observed in 1.01% and 1.02% of subjects, respectively. In the multivariable analysis, these lesions were significantly associated with moderate/heavy smoking (OR = 9.0, 95% CI = 2.1–39.1) and heavy drinking (OR = 2.0, 95% CI = 1.1–3.7). Candidiasis and proliferative lesions were observed in 14.09% and 3.80% of the subjects, respectively. These lesions were significantly associated with female gender (OR = 2.2, 95% CI = 1.5–3.2 and OR = 1.7, 95% CI = 1.0–2.8), older age (OR = 22, 95% CI = 8.0–60.8 and OR = 8.9, 95% CI = 3.4–23.7), and low socioeconomic status (OR = 1.9, 95% CI = 1.0–3.5 and OR = 3.0, 95% CI = 1.2–7.2). Conclusions: This population is in need of OML prevention and treatment. Future studies should validate the findings that premalignant lesions are causally related to smoking and alcohol consumption, and that other OML are associated with socioeconomic‐demographic disparities in this and similar populations.     

N-ras mutations are associated with poor prognosis and increased risk of leukemia in myelodysplastic syndrome

To evaluate the clinical significance of N-ras mutations in the myelodysplastic syndrome (MDS) archival bone marrow samples from 252 patients were studied for the presence of N-ras exon I mutations using polymerase chain reaction amplification and differential oligonucleotide hybridization. Subsequently, clinical information about these patients was obtained and analyzed. Of 220 evaluable patients, 20 (9%) had point mutation of N-ras involving codon 12. Individuals with N- ras mutation had a significantly shorter survival period than those who were N-ras negative (P = .02). An increased risk of acute myelogenous leukemia (AML) was also found in patients with N-ras mutations (P = .005). N-ras mutations were not associated with any French-American- British (FAB) subtype, with the presence of increased myeloblasts, or with chromosomal aberrations in the bone marrow. However, the presence of increased bone marrow blasts was strongly associated with poor survival rate and risk of AML (P < .001 for each). After stratifying for the percentage of blasts, N-ras mutations remained significantly associated with shorter survival period (P = .04) and increased risk of AML (P = .02). Bone marrow cytogenetic abnormalities, particularly when multiple abnormalities were present, were significantly associated with a poor prognosis (P < .001). In conclusion, N-ras mutation, although relatively infrequent in MDS, is associated with short survival period and increased probability of developing AML.