Antibody indexes in COVID-19 convalescent plasma donors: Unanswered questions.

OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is characterized by high contagiousness, as well as variable clinical manifestations and immune responses. The antibody response to SARS-CoV-2 is directly related to viral clearance and the antibodies' ability to neutralize the virus and confer long-term immunity. Nevertheless, the response can also be associated with disease severity and evolution. This study correlated the clinical characteristics of convalescent COVID-19 patients with immunoglobulin A (IgA) and IgG anti-SARS-CoV-2 antibodies. METHODS: This study included 51 COVID-19 health care professionals who were candidates for convalescent plasma donation from April to June 2020. The subjects had symptomatic COVID-19 with a polymerase chain reaction-confirmed diagnosis. We measured anti-SARS-CoV-2 IgA and IgG antibodies after symptom recovery, and the subjects were classified as having mild, moderate, or severe symptoms. RESULTS: Anti-SARS-CoV-2 antibodies were positive in most patients (90.2%). The antibody indexes for IgA and IgG did not differ significantly between patients presenting with mild or moderate symptoms. However, they were significantly higher in patients with severe symptoms. CONCLUSIONS: Our study showed an association between higher antibody indexes and severe COVID-19 cases, and several hypotheses regarding the association of the antibody dynamics and severity of the disease in SARS-CoV-2 infection have been raised, although many questions remain unanswered.

Serologic evidence of West Nile virus and Saint Louis encephalitis virus in horses from Southern Brazil.

Flaviviruses as West Nile virus (WNV), Saint Louis encephalitis virus (SLEV), Ilhéus virus (ILHV), and Rocio virus (ROCV) are previously reported in different Brazilian regions, but studies in Southern Brazil are still scarce. To improve the information regarding flaviviruses in Southern Brazil, horse serum samples were analyzed using RT-qPCR and a commercial ELISA-Ab against WNV followed by PRNT75. All 1000 samples analyzed by real-time RT-PCR resulted negative. The 465 subsampled samples were analyzed by a commercial ELISA-Ab against WNV, and the 18.5% (86/465) positive samples were further analyzed by PRNT75. In the PRNT75, 13/86 and 2/86 horses were positive for SLEV and WNV, respectively. It was observed that 5.8% (13/226) of the farms presented at least one positive animal for SLEV in PRNT75, whereas 0.9% (2/226) for WNV. Apart from the lower seroprevalences identified when compared to data previously reported in other Brazilian regions, our results suggest that public health professionals must be aware of the presence of these potential zoonotic pathogens.

Antibody indexes in COVID-19 convalescent plasma donors: Unanswered questions

OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is characterized by high contagiousness, as well as variable clinical manifestations and immune responses. The antibody response to SARS-CoV-2 is directly related to viral clearance and the antibodies' ability to neutralize the virus and confer long-term immunity. Nevertheless, the response can also be associated with disease severity and evolution. This study correlated the clinical characteristics of convalescent COVID-19 patients with immunoglobulin A (IgA) and IgG anti-SARS-CoV-2 antibodies. METHODS: This study included 51 COVID-19 health care professionals who were candidates for convalescent plasma donation from April to June 2020. The subjects had symptomatic COVID-19 with a polymerase chain reaction-confirmed diagnosis. We measured anti-SARS-CoV-2 IgA and IgG antibodies after symptom recovery, and the subjects were classified as having mild, moderate, or severe symptoms. RESULTS: Anti-SARS-CoV-2 antibodies were positive in most patients (90.2%). The antibody indexes for IgA and IgG did not differ significantly between patients presenting with mild or moderate symptoms. However, they were significantly higher in patients with severe symptoms. CONCLUSIONS: Our study showed an association between higher antibody indexes and severe COVID-19 cases, and several hypotheses regarding the association of the antibody dynamics and severity of the disease in SARS-CoV-2 infection have been raised, although many questions remain unanswered.

Partial 5p Gain and 15q Loss in Three Patients from a Family with a t(5;15)(p13.3;q26.3) Translocation.

Several patients with 5p duplication or 15q deletion have been reported in the literature, involving different chromosome regions and clinical features. Here, we describe a family in which we identified a 30-Mb 5p15.33p13.3 gain and a 2.5-Mb 15q26.3 loss in 3 individuals, due to a balanced familial translocation between chromosomes 5p and 15q. They presented a similar combination of clinical findings related to their genetic imbalances, but there were also phenotypic differences between them. Our analyses show that their clinical picture is mostly caused by the loss in 15q and not the gain in 5p, despite its much larger size. Our findings suggest that other genes, besides the IGF1R gene, in the 15q26.3 region, such as the CHSY1 gene, may have a great impact on the clinical picture of the syndrome. Our data emphasize the importance of detailed cytogenomic and clinical analyses for an accurate diagnosis, prognosis, and genetic counseling, providing an opportunity to improve genotype-phenotype correlations of patients with partial 5p duplication and 15q deletion syndromes.

Malan syndrome in a patient with 19p13.2p13.12 deletion encompassing NFIX and CACNA1A genes: Case report and review of the literature.

BACKGROUND: Malan syndrome is a recently introduced overgrowth disorder described in a limited number of individuals. Haploinsufficiency and also point mutations of NFIX gene have been proposed as its leading causative mechanism, however, due to the limited number of cases and different deletion sizes, genotype/phenotype correlations are still limited. METHODS: Here, we report the first Brazilian case of Malan syndrome caused by a 990 kb deletion in 19p13.2p13.12, focusing on clinical and behavioral aspects of the syndrome. RESULTS: The patient presented with macrocephaly, facial dysmorphisms, hypotonia, developmental delay, moderate thoracolumbar scoliosis, and seizures. The intellectual and behavioral assessments showed severe cognitive, language, and adaptive functions impairments. The 19p deleted region of our patient encompasses NFIX, CACNA1A, which seems to be related to a higher frequency of seizures among individuals with microdeletions in 19p13.2, and 15 other coding genes, including CC2D1A and NACC1, both known to be involved in neurobiological process and pathways. CONCLUSION: Deletions involving NFIX gene should be considered in patients with overgrowth during childhood, macrocephaly, developmental delay, and seizures, as well as severe intellectual disability.

Deletion of Chromosome 13 due to Different Rearrangements and Impact on Phenotype.

Patients with deletion of chromosome 13 present with variable clinical features, and the correlation between phenotype and genomic aberration is not well established in the literature, mainly due to variable sizes of the deleted segments and inaccuracy of breakpoint mapping. In order to improve the genotype-phenotype correlation, we obtained clinical and cytogenomic data from 5 Brazilian patients with different chromosome 13 deletions characterized by G-banding and array techniques. Breakpoints were nonrecurrent, with deletion sizes ranging from 3.8 to 43.3 Mb. Our patients showed some classic features associated with 13q deletion, independent of the location and size of the deletion: hypotonia, growth delay, psychomotor developmental delay, microcephaly, central nervous system anomalies, and minor facial dysmorphism as well as urogenital and limb abnormalities. Comparisons between the literature and our patients' data allowed us to narrow the critical regions that were previously reported for microphthalmia and urogenital abnormalities, indicating that gene haploinsufficiency of ARHGEF7, PCDH9 and DIAPH3, of MIR17HG and GPC6, and of EFNB2 may contribute to microcephaly, cardiovascular disease, and urogenital abnormalities, respectively. The knowledge about genes involved in the phenotypic features found in 13q deletion patients may help us to understand how the genes interact and contribute to their clinical phenotype, improving the patient's clinical follow-up.

Complex Small Supernumerary Marker Chromosome Leading to Partial 4q/21q Duplications: Clinical Implication and Review of the Literature.

Complex small marker chromosomes (sSMCs) consist of chromosomal material derived from more than 1 chromosome. Complex sSMCs derived from chromosomes 4 and 21 are rare, with only 7 cases reported. Here, we describe a patient who presented with a complex sSMC derived from a maternal translocation between chromosomes 4 and 21, which was revealed by G-banding, MLPA, and array techniques. The marker chromosome der(21)t(4;21)(q32.1; q21.2)mat is composed of a 25.6-Mb 21pterq21.2 duplication and a 32.1-Mb 4q32.1q35.2 duplication. In comparison to patients with sSMCs derived from chromosomes 4 and 21, our patient showed a similar phenotype with neuropsychomotor developmental delay and facial dysmorphism as the most important finding, being a composition of the findings found in pure 4q and 21q duplications. The wide range of phenotypes associated with sSMCs emphasizes the importance of detailed cytogenomic analyses for an accurate diagnosis, prognosis, and genetic counseling.

Miller-Dieker Syndrome due to a 5.5-Mb 17p Deletion in a 17;Y Pseudodicentric Chromosome.

Miller-Dieker syndrome (MDS) is a contiguous gene deletion syndrome in which almost all patients present de novo 17p13.3 deletions. We report on a male infant with MDS and an unusual unbalanced translocation involving chromosomes Y and 17 that resulted in a large 5.5-Mb 17pterp13.2 deletion and a karyotype with 45 chromosomes. Apart from the deletion of the MDS critical region, the deletion of additional distal genes seemed to have no major influence on the patient's phenotype, since he did not show any unusual clinical findings that are not commonly described in MDS patients.

PRODH polymorphisms, cortical volumes and thickness in schizophrenia.

Schizophrenia is a neurodevelopmental disorder with high heritability. Several lines of evidence indicate that the PRODH gene may be related to the disorder. Therefore, our study investigates the effects of 12 polymorphisms of PRODH on schizophrenia and its phenotypes. To further evaluate the roles of the associated variants in the disorder, we have conducted magnetic resonance imaging (MRI) scans to assess cortical volumes and thicknesses. A total of 192 patients were evaluated using the Structured Clinical Interview for DSM-IV (SCID), Positive and Negative Syndrome Scale (PANSS), Calgary Depression Scale, Global Assessment of Functioning (GAF) and Clinical Global Impression (CGI) instruments. The study included 179 controls paired by age and gender. The samples were genotyped using the real-time polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP)-PCR and Sanger sequencing methods. A sample of 138 patients and 34 healthy controls underwent MRI scans. One polymorphism was associated with schizophrenia (rs2904552), with the G-allele more frequent in patients than in controls. This polymorphism is likely functional, as predicted by PolyPhen and SIFT, but it was not associated with brain morphology in our study. In summary, we report a functional PRODH variant associated with schizophrenia that may have a neurochemical impact, altering brain function, but is not responsible for the cortical reductions found in the disorder.

ZDHHC8 gene may play a role in cortical volumes of patients with schizophrenia.

ZDHHC8 rs175174 polymorphism is located in 22q11.2 region and its role in brain volume has not been fully addressed. A total of 282 schizophrenia patients and 379 controls were genotyped. A sample of 138 patients underwent brain MRI scan. No association was found between schizophrenia and genotypes. Nevertheless, GG-genotype carriers presented gray matter volume (GMV) reduction in frontal lobe compared to A-allele carriers, and cerebellar hemispheres GMV reductions were found in G-allele carriers compared to AA-genotype. Moreover, A-allele carriers presented posterior brain GMV reductions when compared to GG-genotype. These data suggest that ZDHHC8 may play a role in cortical volumes.

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.

22q11.2 deletion in patients with conotruncal heart defect and del22q syndrome phenotype.

BACKGROUND: The 22q11.2 deletion syndrome is the most frequent human microdeletion syndrome. The phenotype is highly variable, being characterized by conotruncal heart defect, facial dysmorphisms, velopharyngeal insufficiency, learning difficulties and mental retardation. OBJECTIVE: The objective of this study was to investigate the frequency of deletion 22q11.2 in a Brazilian sample of individuals with isolated conotruncal heart defect and 22q11.2 deletion syndrome phenotype. METHODS: Twenty-nine patients were studied by classical cytogenetics, by fluorescence in situ hybridization (FISH), and by molecular techniques. RESULTS: Cytogenetic analysis by G-banding revealed a normal karyotype in all patients except one who presented a 47,XX,+idic(22)(q11.2) karyotype. Using molecular techniques, a deletion was observed in 25% of the patients, all exhibiting a 22q11.2 deletion syndrome phenotype. In none of the cases the deletion was inherited from the parents. The frequency of 22q11.2 deletion was higher in patients with the clinical spectrum of the 22q11.2 deletion syndrome than in patients with isolated conotruncal heart defect. CONCLUSION: Investigating the presence of the deletion and its correlation with the patients' clinical data can help the patients and their families to have a better genetic counseling and more adequate clinical follow-up.

Deleção 22q11.2 em pacientes com defeito cardíaco conotruncal e fenótipo da síndrome da deleção 22q11.2 / Deleción 22q11.2 en pacientes con defecto cardiaco conotruncal y fenotipo del síndrome de la deleción 22q11.2 / 22q11.2 deletion in patients with conotruncal heart defect and del22q syndrome phenotype

FUNDAMENTO: A síndrome da deleção 22q11.2 é a mais freqüente síndrome de microdeleção humana. O fenótipo é altamente variável e caracterizado por defeito cardíaco conotruncal, dismorfias faciais, insuficiência velofaríngea, dificuldade de aprendizagem e retardo mental. OBJETIVO: O objetivo deste trabalho foi investigar a freqüência da deleção 22q11.2 em uma amostra brasileira de indivíduos portadores de cardiopatia conontrucal isolada e do fenótipo da síndrome da deleção 22q11.2. MÉTODOS: Vinte e nove pacientes foram estudados por meio de citogenética clássica, por hibridação in situ fluorescente (FISH) e por técnicas moleculares. RESULTADOS: A análise citogenética por meio de bandamento G revelou cariótipo normal em todos os pacientes, com exceção de um que apresentou cariótipo 47,XX,+idic(22)(q11.2). Com o uso de técnicas moleculares, a deleção foi observada em 25 por cento dos pacientes, todos portadores do fenótipo da síndrome da deleção 22q11.2. Em nenhum dos casos, a deleção foi herdada dos pais. A freqüência da deleção 22q11.2 foi maior no grupo de pacientes portadores do espectro clínico da síndrome da deleção 22q11.2 do que no grupo de pacientes com cardiopatia conotruncal isolada. CONCLUSÃO: A investigação da presença da deleção e sua correlação com os dados clínicos dos pacientes podem auxiliar os pacientes e suas famílias a terem um melhor aconselhamento genético e um seguimento clínico mais adequado.

BACKGROUND: The 22q11.2 deletion syndrome is the most frequent human microdeletion syndrome. The phenotype is highly variable, being characterized by conotruncal heart defect, facial dysmorphisms, velopharyngeal insufficiency, learning difficulties and mental retardation. OBJECTIVE: The objective of this study was to investigate the frequency of deletion 22q11.2 in a Brazilian sample of individuals with isolated conotruncal heart defect and 22q11.2 deletion syndrome phenotype. METHODS: Twenty-nine patients were studied by classical cytogenetics, by fluorescence in situ hybridization (FISH), and by molecular techniques. RESULTS: Cytogenetic analysis by G-banding revealed a normal karyotype in all patients except one who presented a 47,XX,+idic(22)(q11.2) karyotype. Using molecular techniques, a deletion was observed in 25 percent of the patients, all exhibiting a 22q11.2 deletion syndrome phenotype. In none of the cases the deletion was inherited from the parents. The frequency of 22q11.2 deletion was higher in patients with the clinical spectrum of the 22q11.2 deletion syndrome than in patients with isolated conotruncal heart defect. CONCLUSION: Investigating the presence of the deletion and its correlation with the patients' clinical data can help the patients and their families to have a better genetic counseling and more adequate clinical follow-up.

FUNDAMENTO: El síndrome de la deleción 22q11.2 es el más frecuente síndrome de microdeleción humana. El fenotipo, altamente variable, se caracteriza por defecto cardiaco conotruncal, dismorfias faciales, insuficiencia velofaríngea, dificultad de aprendizaje y retardo mental. OBJETIVO: El objetivo de este trabajo fue investigar la frecuencia tanto de la deleción 22q11.2 en una muestra brasileña de individuos portadores de cardiopatía conotrucal aislada, como del fenotipo del síndrome de la delación 22q11.2. MÉTODOS: Se estudiaron a 29 pacientes por medio de citogenética clásica, por hibridación in situ fluorescente (FISH) y también por técnicas moleculares. RESULTADOS: El análisis citogenético por medio de bandeo G reveló cariotipo normal en todos los pacientes, con excepción de uno, que presentó cariotipo 47,XX,+idic(22)(q11.2). Con la utilización de técnicas moleculares, se observó la deleción en el 25 por ciento de los pacientes, todos portadores del fenotipo del síndrome de la deleción 22q11.2. En ningún de los casos, la deleción se heredó de los padres. La frecuencia de la deleción 22q11.2 en el grupo de pacientes portadores del espectro clínico de este síndrome resultó mayor que en el grupo de pacientes con cardiopatía conotruncal aislada. CONCLUSIÓN: La investigación de la presencia de deleción y su correlación con los datos clínicos de los pacientes pueden auxiliar los pacientes y sus familias a tener un mejor aconsejamiento genético, así como un seguimiento clínico más adecuado.

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.

Atypical 22q11.2 deletion in a patient with DGS/VCFS spectrum.

Deletions in region 22q11.2 usually occur between two low copy repeat regions (LCRs), which are preferred chromosome sites for rearrangements. Most of the deletions encompass the same approximately 3 or approximately 1.5 Mb region, with breakpoints at LCR A and D or at LCR A and B, respectively. We report on a patient with clinical features of the 22q deletion syndrome who presents a novel, atypical deletion, smaller than 1.5 Mb, with distal breakpoint in LCR B and proximal breakpoint within no known LCR site.

Deletion 22q11.2: report of a complex meiotic mechanism of origin.

We report on the case of a patient with a typical de novo 3 Mb 22q11.2 deletion. Haplotype reconstruction of the family, using polymorphic markers flanking the deleted region, demonstrated a complex mechanism of origin of the deletion, involving one intrachromosomal and two interchromosomal events.

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.