ABSTRACT
Congenital aniridia is a rare genetic disorder characterized by varying degrees of iris hypoplasia that are associated with additional ocular abnormalities. More than 90% of the causal mutations identified are found in the PAX6 gene, a transcription factor of critical importance in the process of neurogenesis and ocular development. Here, we investigate clinical, molecular, and craniofacial features of a large Brazilian family with congenital aniridia. Among the 56 eyes evaluated, phenotype variation encompassed bilateral total aniridia to mild iris defects with extensive variation between eyes of the same individual. PAX6 molecular screening indicated a heterozygous splice mutation (c.141 + 1G>A). Thus, we hypothesize that this splicing event may cause variation in the expression of the wild-type transcript, which may lead to the observed variation in phenotype. Affected individuals were more brachycephalic, even though their face height and cephalic circumference were not significantly different when compared to those of non-affected relatives. From this, we infer that the head shape of affected subjects may also be a result of the PAX6 splice-site mutation. Our data summarize the clinical variability associated with the ocular phenotype in a large family with aniridia, and help shed light on the role of PAX6 in neurocranial development.
Subject(s)
Aniridia/genetics , Aniridia/pathology , Craniofacial Abnormalities/pathology , Eye Abnormalities/pathology , Eye Proteins/genetics , Homeodomain Proteins/genetics , Paired Box Transcription Factors/genetics , Phenotype , Repressor Proteins/genetics , Adolescent , Adult , Aged , Analysis of Variance , Base Sequence , Brazil , Child , Female , Humans , Male , Middle Aged , Molecular Sequence Data , Mutation/genetics , PAX6 Transcription Factor , Pedigree , Sequence Analysis, DNAABSTRACT
BACKGROUND: Inhabitants of slum settlements represent a significant proportion of the population at risk for pneumococcal disease in developing countries. METHODS: We conducted a household survey of pneumococcal carriage among residents of a slum community in the city of Salvador, Brazil. RESULTS: Among 262 subjects, 95 (36%) were colonized with Streptococcus pneumoniae. Children <5 years of age (OR, 8.0; 95% CI, 3.5-18.6) and those who attended schools (OR, 2.7, 95% CI, 1.2-6.0) had significantly higher risk of being colonized. Of 94 isolates obtained from colonized individuals, 51% had serotypes included in the seven-valent pneumococcal conjugate vaccine. Overall, 10% (9 of 94 isolates) were nonsusceptible to penicillin and 28% (27 of 94 isolates) were resistant to cotrimoxazole. BOX-PCR, PFGE and MLST analyses found that 44% of the carriage isolates belonged to 14 distinct clonal groups. Strains of the same clonal group were isolated from multiple members of 9 out of the 39 study households. Nineteen carriage isolates had genotypes that were the same as those identified among 362 strains obtained from active surveillance for meningitis. CONCLUSIONS: The study's findings indicate that there is significant intra- and inter-household spread of S. pneumoniae in the slum community setting. However, a limited number of clones encountered during carriage among slum residents were found to cause invasive disease.
Subject(s)
Carrier State/epidemiology , Carrier State/transmission , Streptococcus pneumoniae/classification , Streptococcus pneumoniae/isolation & purification , Adolescent , Adult , Age Factors , Anti-Bacterial Agents/pharmacology , Bacterial Typing Techniques , Brazil/epidemiology , Carrier State/microbiology , Child , Child, Preschool , Cluster Analysis , DNA Fingerprinting , DNA, Bacterial/genetics , Drug Resistance, Bacterial , Female , Genotype , Heptavalent Pneumococcal Conjugate Vaccine , Humans , Infant , Male , Meningococcal Vaccines/immunology , Microbial Sensitivity Tests , Pneumococcal Vaccines/immunology , Poverty Areas , Risk Factors , Schools , SerotypingABSTRACT
The vibrational spectrum of H2O was calculated at MP2/6-31G(extended) and MP2/6-311G* levels taking into account anharmonicities through a simple approach to second-order perturbation theory in which molecular energy and dipole moment are expanded as Taylor series in normal coordinates with no cross terms, to simplify calculations. The series coefficients are obtained separately for each normal coordinate through polynomial regression of calculated single point property values corresponding to a few distorted molecular geometries. The energy coefficients are used to calculate the harmonic frequencies and the chi(ii) anharmonicity constants, and so the band origins. For the band intensities, second-order perturbation theory equations derived earlier for diatomic molecules are used for each mode. Estimated frequencies have accuracy equivalent to those of previous complete perturbation calculations at the same ab initio levels, being at most 2.6% above the experimental values for the MP2/6-31G(extended) level. The fundamental intensity estimates are equivalent to those for the complete treatments, with the exception of that at MP2/6-31G(extended) level for the bending mode, which is 7% above the experimental value. Estimated overtone intensities by both complete treatments and the simple approach may still differ in magnitude from the experimental values, though to a lesser extent for the formers.
