Molecular analysis of holoprosencephaly in South America

Holoprosencephaly (HPE) is a spectrum of brain and facial malformations primarily reflecting genetic factors, such as chromosomal abnormalities and gene mutations. Here, we present a clinical and molecular analysis of 195 probands with HPE or microforms; approximately 72% of the patients were derived from the Latin American Collaborative Study of Congenital Malformations (ECLAMC), and 82% of the patients were newborns. Alobar HPE was the predominant brain defect in almost all facial defect categories, except for patients without oral cleft and median or lateral oral clefts. Ethmocephaly, cebocephaly, and premaxillary agenesis were primarily observed among female patients. Premaxillary agenesis occurred in six of the nine diabetic mothers. Recurrence of HPE or microform was approximately 19%. The frequency of microdeletions, detected using Multiplex Ligation-dependant Probe Amplification (MLPA) was 17% in patients with a normal karyotype. Cytogenetics or QF-PCR analyses revealed chromosomal anomalies in 27% of the probands. Mutational analyses in genes SHH, ZIC2, SIX3 and TGIF were performed in 119 patients, revealing eight mutations in SHH, two mutations in SIX3 and two mutations in ZIC2. Thus, a detailed clinical description of new HPE cases with identified genetic anomalies might establish genotypic and phenotypic correlations and contribute to the development of additional strategies for the analysis of new cases.250262Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Telehealth Initiative to Enhance Primary Care Access in Brazil (UBS+Digital Project): Multicenter Prospective Study

BackgroundBrazil faces significant inequities in health care access, particularly in remote communities. The Brazilian Unified Health System is struggling to deliver adequate health care to its vast population. Telehealth, regulated in Brazil starting in 2022, emerged as a solution to improve access and quality of care. Thus, the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, in partnership with the Agência Brasileira de Apoio à Gestão do Sistema Único de Saúde, created the Unidade Básica de Saúde (UBS)+Digital project, which aimed to mitigate the lack of medical care in remote areas of Brazil by providing teleconsultation in primary health units (PHUs) across the country. Through teletraining and digital health strategies, the initiative enabled health care professionals to provide remote assistance, improving access to medical care. ObjectiveTo describe the implementation and results of the UBS+Digital project, a telehealth initiative focused on training health care professionals, providing teleconsultations, and monitoring key performance indicators among PHUs in Brazil. MethodsThe study examined 15 Brazilian PHUs using a multicenter, prospective design. Data were collected through anonymous surveys of patients and physicians, which were recorded in the REDCap (Research Electronic Data Capture) database. PHUs were selected based on criteria such as the absence of an on-site physician and existing technological infrastructure. Synchronous and asynchronous training was provided, focusing on digital health and teleconsultation skills. In loco training included workshops and community events to share experiences and foster local engagement. A community of practice facilitated ongoing knowledge exchange. Teleconsultations followed the person-centered clinical method and Calgary-Cambridge methodology. Key performance indicators were monitored by a dashboard to guide continuous improvement. The transition of operations was managed based on physician availability and project duration. Microcosting analysis assessed the project’s economic impact using Brazilian guidelines, with statistical analysis performed using Jamovi software. ResultsFrom March to November 2023, the project conducted 6312 telehealth sessions. A total of 342 professionals were trained, including participants from all three training modalities that were implemented. The Net Promoter Score for teleconsultations was 97, indicating excellent service quality. Of the teleconsultations, 65.3% (4009/6140) were prescheduled, and 34.7% (2130/6140) were on demand, depending on the family health team organization. Teleconsultations resolved 85% (5219/6140) of cases, with 15% (921/6140) requiring in-person referrals or emergency care. The average absenteeism rate was 15% (1083/7223), and consultation durations were between 15 and 20 minutes, suggesting potential adjustments in scheduling. ConclusionsThe results highlight the effectiveness of telehealth programs in primary care settings with limited medical professionals. The UBS+Digital project demonstrated that telehealth can enhance health care access, presenting a pioneering model within the Brazilian Unified Health System for digital primary care

Molecular analysis of holoprosencephaly in South America

Submitted by Santos Bárbara ([email protected]) on 2015-03-03T13:20:16Z No. of bitstreams: 1 Molecular analysis of holoprosencephaly in South America.pdf: 1134600 bytes, checksum: ca8b31fc87aa2e99d5a446f2722eba78 (MD5)Approved for entry into archive by Santos Bárbara ([email protected]) on 2015-03-03T13:20:29Z (GMT) No. of bitstreams: 1 Molecular analysis of holoprosencephaly in South America.pdf: 1134600 bytes, checksum: ca8b31fc87aa2e99d5a446f2722eba78 (MD5)Approved for entry into archive by Santos Bárbara ([email protected]) on 2015-03-03T14:00:31Z (GMT) No. of bitstreams: 1 Molecular analysis of holoprosencephaly in South America.pdf: 1134600 bytes, checksum: ca8b31fc87aa2e99d5a446f2722eba78 (MD5)Made available in DSpace on 2015-03-03T14:00:31Z (GMT). No. of bitstreams: 1 Molecular analysis of holoprosencephaly in South America.pdf: 1134600 bytes, checksum: ca8b31fc87aa2e99d5a446f2722eba78 (MD5) Previous issue date: 2014Universidade Federal do Rio de Janeiro. Departamento de Genética. Estudo Colaborativo Latino Americano de Malformações Congênitas. Rio de Janeiro, RJ, Brasil. / Instituto Nacional de Genética Médica Populacional, Rio de Janeiro, RJ, Brasil.Universidade Federal do Estado do Rio de Janeiro. Departamento de Genética e Biologia Molecular. Rio de Janeiro, RJ, Brasil.Universidade do Estado do Rio de Janeiro. Instituto de Biologia Roberto Alcantara Gomes. Departamento de Genética. Rio de Janeiro, RJ, Brasil.Instituto Cândida Vargas. Maternidade Cândida Vargas. João Pessoa, PB, Brasil.Centro di Consulenza Genetica e di Teratologia della Riproduzione. Dipartimento Materno Infantile. ARNAS Garibaldi Nesima. Catania, CT, Italy.Universidade Estadual de Campinas. Departamento de Genética Médica. Campinas, SP, Brasil.Hospital das Clínicas de Porto Alegre. Serviço de Genética Médica. Porto Alegre, RS, Brasil.Registro Campano Difetti Congeniti. Azienda Ospedaliera “Gaetano Rummo”. Benevento, BN, Italy.Fundação Oswaldo Cruz. Instituto Fernandes Figueira. Centro de Genética Médica. Rio de Janeiro, RJ, Brasil.Universidade Federal do Estado do Rio de Janeiro. Departamento de Genética e Biologia Molecular. Rio de Janeiro, RJ, Brasil. / Fundação Oswaldo Cruz. Estudo Colaborativo Latino Americano de Malformações Congênitas. Laboratório de Epidemiologia de Defeitos Congênitos. Rio de Janeiro, RJ, Brasil.Instituto Nacional de Câncer. Programa de Genética. Rio de Janeiro, RJ, Brasil.Instituto Nacional de Câncer. Programa de Genética. Rio de Janeiro, RJ, Brasil.Instituto Nacional de Genética Médica Populacional, Rio de Janeiro, RJ, Brasil. / Centro de Educación Médica e Investigación Clínica. Estudio Colaborativo Latino Americano de Malformaciones Congenitas. Buenos Aires, Argentina.Universidade Federal do Rio de Janeiro. Departamento de Genética. Estudo Colaborativo Latino Americano de Malformações Congênitas. Rio de Janeiro, RJ, Brasil. / Instituto Nacional de Genética Médica Populacional, Rio de Janeiro, RJ, Brasil.Holoprosencephaly (HPE) is a spectrum of brain and facial malformations primarily reflecting genetic factors, such as chromosomal abnormalities and gene mutations. Here, we present a clinical and molecular analysis of 195 probands with HPE or microforms; approximately 72% of the patients were derived from the Latin American Collabo-rative Study of Congenital Malformations (ECLAMC), and 82% of the patients were newborns. Alobar HPE was the predominant brain defect in almost all facial defect categories, except for patients without oral cleft and median or lat-eral oral clefts. Ethmocephaly, cebocephaly, and premaxillary agenesis were primarily observed among female pa-tients. Premaxillary agenesis occurred in six of the nine diabetic mothers. Recurrence of HPE or microform was approximately 19%. The frequency of microdeletions, detected using Multiplex Ligation-dependant Probe Amplifica-tion (MLPA) was 17% in patients with a normal karyotype. Cytogenetics or QF-PCR analyses revealed chromosomal anomalies in 27% of the probands. Mutational analyses in genesSHH,ZIC2,SIX3andTGIFwere performed in 119 patients, revealing eight mutations inSHH,two mutations inSIX3and two mutations inZIC2. Thus, a detailed clinical description of new HPE cases with identified genetic anomalies might establish genotypic and phenotypic correla-tions and contribute to the development of additional strategies for the analysis of new cases

Molecular analysis of holoprosencephaly in South America

Holoprosencephaly (HPE) is a spectrum of brain and facial malformations primarily reflecting genetic factors, such as chromosomal abnormalities and gene mutations. Here, we present a clinical and molecular analysis of 195 probands with HPE or microforms; approximately 72% of the patients were derived from the Latin American Collabo-rative Study of Congenital Malformations (ECLAMC), and 82% of the patients were newborns. Alobar HPE was the predominant brain defect in almost all facial defect categories, except for patients without oral cleft and median or lat-eral oral clefts. Ethmocephaly, cebocephaly, and premaxillary agenesis were primarily observed among female pa-tients. Premaxillary agenesis occurred in six of the nine diabetic mothers. Recurrence of HPE or microform was approximately 19%. The frequency of microdeletions, detected using Multiplex Ligation-dependant Probe Amplifica-tion (MLPA) was 17% in patients with a normal karyotype. Cytogenetics or QF-PCR analyses revealed chromosomal anomalies in 27% of the probands. Mutational analyses in genesSHH,ZIC2,SIX3andTGIFwere performed in 119 patients, revealing eight mutations inSHH,two mutations inSIX3and two mutations inZIC2. Thus, a detailed clinical description of new HPE cases with identified genetic anomalies might establish genotypic and phenotypic correla-tions and contribute to the development of additional strategies for the analysis of new cases

New <b><i>SHH</i></b> and Known <b><i>SIX3</i></b> Variants in a Series of Latin American Patients with Holoprosencephaly

Holoprosencephaly (HPE) is the failure of the embryonic forebrain to develop into 2 hemispheres promoting midline cerebral and facial defects. The wide phenotypic variability and causal heterogeneity make genetic counseling difficult. Heterozygous variants with incomplete penetrance and variable expressivity in the &lt;i&gt;SHH&lt;/i&gt;, &lt;i&gt;SIX3&lt;/i&gt;, &lt;i&gt;ZIC2&lt;/i&gt;, and &lt;i&gt;TGIF1&lt;/i&gt; genes explain ∼25% of the known causes of nonchromosomal HPE. We studied these 4 genes and clinically described 27 Latin American families presenting with nonchromosomal HPE. Three new &lt;i&gt;SHH&lt;/i&gt; variants and a third known &lt;i&gt;SIX3&lt;/i&gt; likely pathogenic variant found by Sanger sequencing explained 15% of our cases. Genotype-phenotype correlation in these 4 families and published families with identical or similar driver gene, mutated domain, conservation of residue in other species, and the type of variant explain the pathogenicity but not the phenotypic variability. Nine patients, including 2 with &lt;i&gt;SHH&lt;/i&gt; pathogenic variants, presented benign variants of the &lt;i&gt;SHH&lt;/i&gt;, &lt;i&gt;SIX3&lt;/i&gt;, &lt;i&gt;ZIC2&lt;/i&gt;, and &lt;i&gt;TGIF1&lt;/i&gt; genes with potential alteration of splicing, a causal proposition in need of further studies. Finding more families with the same &lt;i&gt;SIX3&lt;/i&gt; variant may allow further identification of genetic or environmental modifiers explaining its variable phenotypic expression. </jats:p

Molecular analysis of holoprosencephaly in South America

Holoprosencephaly (HPE) is a spectrum of brain and facial malformations primarily reflecting genetic factors, such as chromosomal abnormalities and gene mutations. Here, we present a clinical and molecular analysis of 195 probands with HPE or microforms; approximately 72% of the patients were derived from the Latin American Collaborative Study of Congenital Malformations (ECLAMC), and 82% of the patients were newborns. Alobar HPE was the predominant brain defect in almost all facial defect categories, except for patients without oral cleft and median or lateral oral clefts. Ethmocephaly, cebocephaly, and premaxillary agenesis were primarily observed among female patients. Premaxillary agenesis occurred in six of the nine diabetic mothers. Recurrence of HPE or microform was approximately 19%. The frequency of microdeletions, detected using Multiplex Ligation-dependant Probe Amplification (MLPA) was 17% in patients with a normal karyotype. Cytogenetics or QF-PCR analyses revealed chromosomal anomalies in 27% of the probands. Mutational analyses in genes SHH, ZIC2, SIX3 and TGIF were performed in 119 patients, revealing eight mutations in SHH, two mutations in SIX3 and two mutations in ZIC2. Thus, a detailed clinical description of new HPE cases with identified genetic anomalies might establish genotypic and phenotypic correlations and contribute to the development of additional strategies for the analysis of new cases