Identifying Genetic Etiology in Patients with Intellectual Disability: An Experience in Public Health Services in Northeastern Brazil.

Intellectual disability (ID) is considered a common neuropsychiatric disorder that affects up to 3% of the population. The etiologic origin of ID may be genetic, environmental, and multifactorial. Chromosomopathies are relatively common among the genetic causes of ID, especially in the most severe cases and those associated with dysmorphic features. Currently, the application of new molecular cytogenetics technologies has increasingly allowed the identification of microdeletions, microduplications, and unbalanced translocations as causes of ID. The objective of this study was to investigate the etiology of ID in patients admitted to a public hospital in Northeastern Brazil. In total, 119 patients with ID who had normal karyotypes and fragile X exams participated in this study. The patients were initially physically examined for microdeletion syndromes and then tested using fluorescence in situ hybridization (FISH), multiplex ligation-dependent probe amplification (MLPA), methylation-sensitive polymerase chain reaction (MS-PCR), and chromosome microarray analysis (CMA), according to clinical suspicion. Patients with no diagnoses after FISH, MLPA, and/or MS-PCR evaluations were subsequently tested by CMA. The rate of etiologic diagnoses of ID in the current study was 28%. FISH diagnosed 25 out of 79 tested (31%), MLPA diagnosed 26 out of 79 tested (32%), MS-PCR diagnosed 7 out of 20 tested (35%), and the single nucleotide polymorphism array diagnosed 6 out of 27 tested (22%). Although the CMA is the most complete and recommended tool for the diagnosis of microdeletions, microduplications, and unbalance translocations in patients with ID, FISH, MLPA, and MS-PCR testing can be used as the first tests for specific syndromes, as long as the patients are first physically screened clinically, especially in the public health networks system in Brazil, where resources are scarce.

Methylphenidate effects on mice odontogenesis and connections with human odontogenesis.

The purpose of this study is to evaluate the effects of Methylphenidate exposure on mice odontogenesis and connect them by bioinformatics with human odontogenesis. Thirty-two pregnant Swiss mice were divided into treated group and control group, which received, respectively, 5 mg/kg of Methylphenidate and saline solution from the 5th to the 17th day of pregnancy. The mouse embryos tooth germs were analyzed through optical microscopy, and the data collected were analyzed statistically by Fisher's exact test. The presence and similarity of Methylphenidate-associated genes (Pharmgkb database) in both organisms and their interaction with dental development genes (AmiGO2 database) were verified on STRING database. Rates of tooth germ malformations were higher in treated than in control group (Control: 18; Treated: 27; p = 0.035). Mouse embryo malformations were connected with 238 interactions between 69 dental development genes with 35 Methylphenidate genes. Fourteen interactions for four Methylphenidate genes with four dental development genes, with human experimental data, were connected with mouse phenotype data. By homology, the interactions and conservation of proteins/genes may indicate similar outcomes for both organisms. The exposure to Methylphenidate during pregnancy affected odontogenesis in mouse embryos and may affect human odontogenesis. The study of malformations in mice, with a bioinformatics approach, could contribute to understanding of the Methylphenidate effect on embryo development. These results may provide novel hypotheses for further testing and reinforce the FDA protocol: as Methylphenidate is included in category C, its use during pregnancy should be considered if the benefits outweigh the risks.

Description of rare mutations and a novel variant in Brazilian patients with Cystic Fibrosis: a case series from a referral center in the Bahia State.

Knowledge of the genetic profile of Cystic Fibrosis (CF) contributes to a better understanding of the genotype/phenotype relationship, particularly in mixed populations such as in Brazil. To describe clinical data of CF patients with rare or not yet observed CFTR gene mutations in Brazil. It was a case series of CF patients followed-up at a referral center. Clinical and laboratory data were obtained through medical records. Molecular analysis of the mutations was performed by conventional methods and/or by next-generation sequencing. Ten patients were studied, seven had five pathogenic mutations without previous description in Brazil (Q1100P, Y109C, A107P, E1409K and K162E), one of which has not yet been reported in patients with CF (A107P). Among the seven patients, three (two siblings) had the second mutant allele of rare occurrence among Brazilians patients (G1069R and 2307insA). Three other patients also had at least one rare variant (V201M, S466X and G1069R). The age of the CF diagnosis ranged from 1 to 190 months in the ten cases and the main clinical manifestations were respiratory symptoms and difficulty in gaining weight. All but one patient presented clinical and/or laboratory data compatible with pancreatic insufficiency. The identification of rare or not yet described CFTR mutations in patients with CF in Brazil highlights the high genetic heterogeneity in this population. Knowledge of the genotypic profile of Brazilian CF patients can contribute to the development of specific mutation panels for the genetic investigation targeting each region of the country, as well as helping to understand the complex genotype/phenotype relationship, especially in mixed populations.