Hipertricose como Marcador Subfenotípico de Retardo Neurológico e Neuromotor

O objetivo do estudo foi investigar na literatura disponível, trabalhos que apresentam a correlação de hipertricose congênita com alterações craniofaciais e envolvimento neurológico e neuromotor em pacientes pediátricos e adultos. A pesquisa foi realizada nas bases de dados Online Mendelian Inheritance in Man (OMIM), Protein e com busca ampliada no Pubmed-NCBI, não foi estabelecido período limítrofe quanto a data de publicação. Os descritores empregados na língua inglesa foram “Hypertrichosis”, “Neurodevelopmental Disorders” e “Craniofacial Abnormalities”. Foram incluídos apenas trabalhos sobre síndromes que tinham associação entre hipertricose, anomalias craniofaciais, neurológicas e neuromotoras. As que não se encaixavam nesses critérios foram excluídas, como trabalhos abordando somente malformações, alterações congênitas e quando citava o Hirsutismo isolado. A pesquisa no OMIM resultou 148 condições que mencionavam hipertricose, destas apenas 27 se encaixaram nos critérios de inclusão. Nota-se características de alterações gerais e de cabeça e pescoço que foram comumente encontradas, entre elas: Hipertricose, deficiência intelectual, retardo mental, palato altamente arqueado, hiperplasia gengival e orelhas dismórficas. Portanto, é de suma importância que o odontólogo esteja atento, saiba identificar e documentar alterações somáticas e faciais, a fim de auxiliar na identificação e confirmação de síndromes, como também proporcionar um diagnóstico mais preciso e melhor desfecho para tratamento das alterações da cavidade bucal.

Ambiguity about Splicing Factor 3b Subunit 3 (SF3B3) and Sin3A Associated Protein 130 (SAP130)

In 2020, three articles were published on a protein that can activate the immune system by binding to macrophage-inducible C-type lectin receptor (Mincle). In the articles, the protein was referred to as ‘SAP130, a subunit of the histone deacetylase complex.’ However, the Mincle ligand the authors aimed to investigate is splicing factor 3b subunit 3 (SF3B3). This splicing factor is unrelated to SAP130 (Sin3A associated protein 130, a subunit of the histone deacetylase-dependent Sin3A corepressor complex). The conclusions in the three articles were formulated for SF3B3, while the researchers used qPCR primers and antibodies against SAP130. We retraced the origins of the ambiguity about the two proteins and found that Online Mendelian Inheritance in Man (OMIM) added a Nature publication on SF3B3 as a reference for Sin3A associated protein 130 in 2016. Subsequently, companies such as Abcam referred to OMIM and the Nature article in their products for both SF3B3 and SAP130. In turn, the mistake by OMIM followed in the persistent and confusing use of ‘SAP130′ (spliceosome-associated protein 130) as an alternative symbol for SF3B3. With this report, we aim to eliminate the persistent confusion and separate the literature regarding the two proteins.

The similarity of inherited diseases (I): clinical similarity within the phenotypic series

Background Mutations of different genes often result in clinically similar diseases. Among the datasets of similar diseases, we analyzed the ‘phenotypic series’ from Online Mendelian Inheritance in Man and examined the similarity of the diseases that belong to the same phenotypic series, because we hypothesize that clinical similarity may unveil shared pathogenic mechanisms. Methods Specifically, for each pair of diseases, we quantified their similarity, based on both number and information content of the shared clinical phenotypes. Then, we assembled the disease similarity network, in which nodes represent diseases and edges represent clinical similarities. Results On average, diseases have high similarity with other diseases of their own phenotypic series, even though about one third of diseases have their maximal similarity with a disease of another series. Consequently, the network is assortative (i.e., diseases belonging to the same series link preferentially to each other), but the series differ in the way they distribute within the network. Specifically, heterophobic series, which minimize links to other series, form islands at the periphery of the network, whereas heterophilic series, which are highly inter-connected with other series, occupy the center of the network. Conclusions The finding that the phenotypic series display not only internal similarity (assortativity) but also varying degrees of external similarity (ranging from heterophobicity to heterophilicity) calls for investigation of biological mechanisms that might be shared among different series. The correlation between the clinical and biological similarities of the phenotypic series is analyzed in Part II of this study1.

Genetics in Ophthalmology

На сегодняшний день в базе данных Online Mendelian Inheritance in Man (OMIM) описано более 6613 заболеваний и фенотипов, 4241 имеют доказанную генетическую основу, не менее 45% вкючают офтальмологические проявления. В статье приведен ряд клинический примеров пациентов с офтальмологическими симптомами различных генетических заболеваний (алкаптонурия, болезнь Штаргардта, синдром микроцефалии с или без хориоретинопатии; астроцитарная гамартома) с целью демонстрации эффективного клинико-диагностического скрининга генетической патологии у пациентов. So far, the Online Mendelian Inheritance in Man (OMIM) database describes more than 6613 diseases and phenotypes, 4241 have a proven genetic basis, 45% of which are combined with ophthalmological manifestations. The article provides a number of clinical examples of patients with ophthalmological manifestations of various genetic diseases (alcaptonuria, Stadgart ‘s disease, microcephaly syndrome with or without choriretinopathy; Astrocytic gamartoma) to demonstrate effective clinical-diagnostic screening of genetic pathology in patients.

A Diagnostic Case Study of a Young Man with Russell-Silver Syndrome and Associated Comorbidities

This is a case study of a young man diagnosed with Russell-Silver Syndrome or RSS for short (Online Mendelian Inheritance in Man® Classification Number #180860) and associated comorbidities. The aim of this paper is to provide diagnostic information about the syndrome with its comorbidities so that educational therapists and other allied professionals working with such individuals will know what to look out for, especially the RSS-associated comorbidities, and in that way, they become better informed in order to know what offer in their Response to Intervention (RtI) for such individuals with RSS.