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In populations that have a high degree of admixture, such as in Brazil, the sole use of ethnicity self-declaration information is not a good method for classifying individuals regarding their ethnicity. Here, we evaluate the relationship of self-declared ethnicities with genomic ancestry and mitochondrial haplogroups in 492 individuals from southeastern Brazil. Mitochondrial haplogroups were obtained by analyzing the hypervariable regions of the mitochondrial DNA (mtDNA), and the genomic ancestry was obtained using 48 autosomal insertion-deletion ancestry informative markers (AIM). Of the 492 individuals, 74.6% self-declared as White, 13.8% as Brown and 10.4% as Black. Classification of the mtDNA haplogroups showed that 46.3% had African mtDNA, and the genomic ancestry analysis showed that the main contribution was European (57.4%). When we looked at the distribution of mtDNA and genomic ancestry according to the self-declared ethnicities from 367 individuals who self-declared as White, 37.6% showed African mtDNA, and they had a high contribution of European genomic ancestry (63.3%) but also a significant contribution of African ancestry (22.2%). Of the 68 individuals who self-declared as Brown, 25% showed Amerindian mtDNA and similar contribution of European and African genomic ancestries. Of the 51 subjects who self-declared as black, 80.4% had African mtDNA, and the main contribution of genomic ancestry was African (55.6%), but they also had a significant proportion of European ancestry (32.1%). The Brazilian population had a uniform degree of Amerindian genomic ancestry, and it was only with the use of genetic markers (autosomal or mitochondrial) that we were able to capture Amerindian ancestry information. Additionally, it was possible to observe a high degree of heterogeneity in the ancestry for both types of genetic markers, which shows the high genetic admixture that is present in the Brazilian population. We suggest that in epidemiological studies, the use of these methods could provide complementary information.

Summary:Purpose: This study aimed to evaluate the sensitivity of the EEG in Angelman syndrome (AS), to verify the age at onset of suggestive EEGs and to study EEG patterns, analyzing variations and comparing our findings with nomenclature previously used.Methods: Seventy EEG and 15 V-EEGs of 26 patients were analyzed. Suggestive EEG patterns of AS were classified in delta pattern (DP), theta pattern (TP), and posterior discharges (PDs). Generic terms were used to simplify the analysis.Results: Suggestive EEGs were observed in 25 (96.2%) patients. DP occurred in 22 patients with four variantshypsarrhythmic-like: irregular, high-amplitude, generalized delta activity (DA) with multifocal epileptiform discharges (EDs); slow variant: regular, high-amplitude, generalized DA with rare EDs; ill-defined slow spike-and-wave: regular, high-amplitude, generalized DA with superimposed EDs characterizing a slow wave, with notched appearance; triphasic-like: rhythmic, moderate-amplitude DA over anterior regions with superimposed EDs. TP was observed in eight patients, as generalized or over the posterior regions. PDs were seen in 19 patients as runs of sharp waves or runs of high-amplitude slow waves with superimposed EDs. TP was the only age-related pattern (younger than 8 years) and observed only in patients with deletion. In 15 patients who had an EEG before the clinical diagnosis, 60% had a suggestive tracing.Conclusions: Although some EEG descriptions are not very detailed, and every author describes findings in a slightly different manner, obviously a common denominator must exist. In this context, EEG seems to be a very sensitive method for the diagnosis of AS, offering an opportunity to corroborate this etiologic diagnosis. Conversely, we do not believe that these patterns may be accounted as specific, except for the delta pattern, which seems to be extremely unusual in other syndromes. Other EEG patterns observed in AS, such as theta activity and PDs, occur in a wide variety of disorders. Nonetheless, their importance for the EEG diagnosis of AS is supported by the fact that they are associated with other features and may be helpful in a proper clinical setting. Key Words: Angelman syndrome-EEG-VariantsEpilepsy-Genetic mechanisms.Angelman syndrome (AS) was originally described in 1965 by a British pediatrician named Harry Angelman, who reported three children with peculiar traits and introduced the term puppet children to name them (1). AS did not attract much attention in medical literature until the 1980s, when advances in the field of genetics led to renewed interest in this syndrome. According to the Consensus for Diagnostic Criteria (2), AS demonstrates, in all cases, impairment of neurologic development, poor or no language acquisition, a peculiar behavioral profile (unprovoked laughter, happy demeanor, hand flapping, hyperactivity, and attention-deficit disorder), and a wide-based AS is caused by multiple genetic mechanisms, all of which affect the maternal chromosome 15q11-q13, a known imprinted region. The kn...

Com o aumento da expectativa de vida, visto hoje em todo o planeta, um maior número de indivíduos alcança uma idade avançada em que a manifestação de doenças neurodegenerativas é mais freqüente. Entre essas, a doença de Alzheimer (DA) é a causa mais freqüente de demência. Os achados mais marcantes na DA, em cérebros de pacientes acometidos pela doença, são as placas senis, os emaranhados neurofibrilares e a extensa perda neuronal. No entanto, existe uma carência generalizada de marcadores biológicos preditivos ou com valor diagnóstico para a DA. Estudos de genética molecular permitiram identificar quatro genes consistentemente associados com o maior risco de desenvolvimento da doença: APP, apoE, PSEN1 e PSEN2. No entanto, inúmeros estudos apontam para papel importante de outros genes, fortalecendo a hipótese de uma doença poligênica e multifatorial. Neste sentido, novas abordagens de estudo têm um futuro promissor, podendo indicar uma vasta população de genes ou alterações moleculares que possam explicar o surgimento da doença, vindo a fornecer as bases para a compreensão da DA e também para o delineamento de novas e mais eficazes abordagens de tratamento ou prevenção da doença. AbstractLaboratório de Neurociências (LIM-27),

Angelman syndrome (AS) is a neurodevelopmental disorder characterized by mental retardation, speech impairment, ataxia, and happy disposition with frequent smiling. AS results from the loss of expression of a maternal imprinted gene, UBE3A, mapped within 15q11-q13 region, due to different mechanisms: maternal deletion, paternal UPD, imprinting center mutation, and UBE3A mutation. Deletion AS patients may exhibit hypopigmentation of skin, eye, and hair correlating with deletion of P gene localized in the distal part of Prader-Willi (PWS)/AS region. Our patient presented developmental delay, severe mental retardation, absence of speech, outbursts of laughter, microcephaly, ataxia, hyperactivity, seizures, white skin, no retinal pigmentation, and gold yellow hair. His parents were of African ancestry. The SNURF-SNRPN methylation analysis confirmed AS diagnosis and microsatellite studies disclosed deletion with breakpoints in BP2 and BP3. All of the 25 exons and flanking introns of the P gene of the patient, his father, and mother were investigated. The patient is hemizygous for the deleted exon 7 of the P gene derived from his father who is a carrier of the deleted allele. Our patient manifests OCA2 associated with AS due to the loss of the maternal chromosome 15 with the normal P allele, and the paternal deletion in the P gene. As various degrees of hypopigmentation are associated with PWS and AS patients, the study of the P gene in a hemizygous state could contribute to the understanding of its effect on human pigmentation during development and to disclose the presence of modifier pigmentation gene(s) in the PWS/AS region.

We had previously described a patient with an overgrowth syndrome and the chromosome constitution 45,XY,t(15q15q) (Wajntal et al., DNA Cell Biol 1993: 12: 227-231). Clinical reassessment and the use of molecular studies, including methylation analysis with an SNRPN probe, microsatellite analyses of D15S11, GABRB3 and D15S113 loci, and fluorescence in situ hybridization (FISH) using the SNRPN and GABRB3 probes, are consistent with a diagnosis of Angelman syndrome (AS) due to paternal isodisomy. This is the fourth report case of a translocation 15q15q with paternal uniparental disomy (UPD). Our findings suggest that some patients with clinical features of AS have hyperphagia and obesity with overgrowth, and that these features should not rule out a diagnosis of AS.

Among 25 patients diagnosed with Angelman syndrome, we detected 21 with deletion and 4 with paternal uniparental disomy (UPD), 2 isodisomies originating by postzygotic error, and 1 MII nondisjunction event. The diagnosis was obtained by molecular techniques, including methylation pattern analysis of exon 1 of SNRPN and microsatellite analysis of loci within and outside the 15q11-q13 region. Most manifestations present in deletion patients are those previously reported. Comparing the clinical data from our and published UPD patients with those with deletions we observed the following: the age of diagnosis is higher in UPD group (average 7 3/12 years), microcephaly is more frequent among deletion patients, UPD children start walking earlier (average age 2 9/12 years), whereas in deletion patients the average is 4 (1/2) years, epilepsy started later in UPD patients (average 5 10/12 years) than in deletion patients (average 1 11/12 years), weight above the 75th centile is reported mainly in UPD patients, complete absence of speech is more common in the deleted (88.9%) than in the UPD patients because half of the children are able to say few words. Thus, besides the abnormalities already described, the UPD patients have somewhat better verbal development, a weight above the 75th centile, and OFC in the upper normal range.

MYH9 polymorphisms have been described to be associated with the risk of CKD in non-diabetic nephropathy, HIV nephropathy and FSGS. Predominating in black descendants, MHY9 genetic variants could partially explain the excess risk of CKD associated with African ancestry. However, recent data suggests that APOL1 gene co-segregate with MYH9, and could be the gene truly associated with CKD risk. In this study, we evaluated the role of MYH9 and APOL1 gene polymorphisms in the risk of CKD in Brazilian patients with lupus nephritis (LN). A retrospective analysis of 196 LN patients was done. MYH9 rs4821480, rs2032487, rs4821481 and rs3752462, APOL 1rs73885319, rs16996616, rs60910145, rs71785313, and APOL3 rs11089781 gene polymorphisms were determined. Genetic ancestry was ascertained both by autossomal ancestry and mitochondrial haplogroup. Primary outcome was defined as doubling of serum creatinine (DC) or end stage renal disease (ESRD). Sixty-two patients presented the PO. In our population, MYH9 and APOL1 were not in LD. None APOL polymorphism was associated with the PO, whereas rs3752462 MYH9 polymorphism showed a positive association (HR3.72, 95%CI 1.47–9.38, p = 0.005). When we analyzed the MYH9 E1 haplotype, the GCCT carriers (1 or 2 alelles present in 29.7% in the PO group vs. 18.5% in controls) showed a significant association to the risk of PO, even after adjustments for baseline estimated creatinine clearance and autossomal ancestry (HR 2.0, 95%CI 1.2–3.4, p = 0.01). Our results show that in our population MYH9, but not APOL1, gene polymorphisms confer an increased risk of CKD in LN patients, independently of race.