Global publication trends in ophthalmic genetics and gene therapy research: A Scientometric analysis / Tendências globais de publicação de pesquisas sobre genética oftálmica e terapia genética: uma análise cientométrica

ABSTRACT Objective: A scientometric analysis produced in ophthalmic genetics and gene therapy research is lacking. The purpose of this study is to present a holistic analysis of ophthalmic genetics literature. Methods: The data used in this study were obtained from the Web of Science (WoS) Core Collection. All published documents between 1975-2019 were included. The data exported from WoS enabled the extensive details of ophthalmic genetics related literature including countries, institutions, authors, citations and keywords. Scientometric network maps of keywords and also country and institution co-authorships were created with free software. Global contributions of the countries to the ophthalmic genetics literature were shown by a graphic. Results: The search query revealed a total of 2322 documents. Most of the documents were original articles (75.75%). USA was the leading country by producing 45.39% of all documents in ophthalmic genetics research followed by UK, Germany, China and France. Pennsylvania University was the most contributing institution in the literature (5.25%) followed by University College London and Moorfields Eye Hospital. The average citations per item was 29.4. The most used keywords over a 40-year period were 'family', 'cell', 'photoreceptor' and 'expression'. Conclusions: USA and UK dominated the ophthalmic genetics research. A substantial increase in the number of published documents in this field were observed after 2010.

RESUMO Objetivo: A literatura carece de análise cienciométrica produzida em genética oftálmica e de pesquisa em terapia genética. O objetivo deste estudo é apresentar uma análise holística da literatura genética oftálmica. Métodos: Os dados utilizados neste estudo foram obtidos na base de dados Web of Science (WoS) Core Collection. Todos os documentos publicados entre 1975 e 2019 foram incluídos na análise. Os dados exportados da WoS viabilizaram acesso a amplos detalhes da literatura relacionada à genética oftálmica, incluindo países, instituições, autores, citações e palavras-chave. Mapas de rede cienciométrica foram criados por meio de software gratuito, com base em palavras-chave e em coautorias de países e instituições. As contribuições globais dos países para a literatura sobre genética oftálmica foram apresentadas em gráfico. Resultados: a busca por pesquisas revelou um total de 2.322 documentos cuja maioria eram artigos originais (75,75%). Os EUA foram o país que mais produziu artigos sobre o tema, com 45,39% de todos os documentos em pesquisa genética oftálmica; ele foi seguido pelo Reino Unido, Alemanha, China e França. A Universidade da Pensilvânia foi a instituição que mais contribuiu para a literatura (5,25%), e foi seguida pela University College London e pelo Moorfields Eye Hospital. A média de citações por item foi de 29,4. As palavras-chave mais usadas em um período de 40 anos foram 'família', 'célula', 'fotorreceptor' e 'expressão'. Conclusões: Os EUA e o Reino Unido dominaram a pesquisa em genética oftálmica. Após 2010, observou-se um aumento substancial no número de documentos publicados nessa área.

Diversity of familial exudative vitreoretinopathy / 中华眼底病杂志

Familial exudative vitreoretinopathy (FEVR) is a hereditary retinal vascular dysplasia. So far, 6 genes have been found to be associated with FEVR: Wnt receptor Frizzled Protein 4, Norrie's disease, co-receptor low-density lipoprotein receptor-related protein 5, tetraspanin 12, zinc finger protein 408, and kinesin family members 11 genes. Its clinical manifestations, pathological processes and genetic patterns are diverse, and it shows the relationship between gene polymorphism and clinical manifestation diversity. It is characterized by different symptoms between the same individual, the same family, and the same gene mutation; different clinical stages and gene mutation types of parents or unilateral genetic children; different clinical characteristics and gene mutation patterns of full-term and premature infant; combined with other eye disease and systemic diseases;double gene mutations and single gene mutations have different clinical manifestations and gene mutation characteristics. A comprehensive understanding of the different clinical manifestations and diverse genetics of FEVR can provide better guidance for the treatment of FEVR.

Role of miRNAs on the Pathophysiology of Cardiovascular Diseases / Papel dos miRNAs na Fisiopatologia das Doenças Cardiovasculares

Abstract MiRNA (or microRNA) is a subclass of non-coding RNAs that is responsible for post-transcriptional gene regulation. It has approximately 22 nucleotides and regulates gene expression in plants and animals at the post-transcriptional level, by the cleavage of a target mRNA or by suppression of its translation. Although many of the processes and mechanisms have not yet been fully elucidated, there is a strong association between miRNA expression and several diseases. It is known that miRNAs are expressed in the cardiovascular system, but their role in cardiovascular diseases (CVDs) has not been clearly established. In this non-systematic review of the literature, we first present the definition of miRNAs and their action at the cellular level. Afterward, we discuss the role of miRNAs as circulating biomarkers of CVDs, and then their role in cardiac remodeling and atherosclerosis. Despite the complexity and challenges, it is crucial to identify deregulated miRNAs in CVDs, as it allows a better understanding of underlying cellular and molecular mechanisms and helps in the development of more accurate diagnostic and prognostic circulating biomarkers, and new therapeutic strategies for different stages of CVDs.

Resumo O miRNA (ou microRNA) constitui uma subclasse de RNAs não codificantes responsáveis pela regulação gênica pós-transcricional. Ele possui aproximadamente 22 nucleotídeos e regula a expressão gênica em plantas e animais ao nível pós-transcricional, pela clivagem de um mRNA alvo ou da repressão de sua tradução. Embora muitos processos e mecanismos ainda não estejam completamente elucidados, existe uma forte associação entre a expressão de miRNAs e diversas doenças que acometem o organismo. Os miRNAs são expressos no sistema cardiovascular, contudo o seu papel no desenvolvimento das doenças cardiovasculares (DCVs) ainda não está totalmente elucidado. Diante disso, realizou-se uma revisão não sistemática da literatura a fim de se discutir a relação entre os miRNAs e as DCVs. Nesta revisão, primeiramente é discutido o que são os miRNAs e a sua ação a nível celular. Após, é discutido o papel dos miRNAs como biomarcadores circulantes de DCVs e então o seu papel no remodelamento cardíaco e na aterosclerose. Apesar da complexidade e dos desafios, a identificação dos miRNAs desregulados nas DCVs é crucial, uma vez que possibilita uma melhor compressão dos mecanismos celulares e moleculares envolvidos, assim como auxilia o desenvolvimento de marcadores circulantes de diagnóstico e prognóstico mais acurados e de novas estratégias terapêuticas para os diferentes estágios da DCV.

Advances in the genetics of familial exudative vitreoretinopathy / 中华眼底病杂志

Familial exudative vitreoretinopathy (FEVR) is a hereditary disease with high geneticheterogeneity,including autosomal dominant inheritance,autosomal recessive inheritance,snd X-linked recessive inheritance.So far,six genes have been found to be associated with FEVR:Wnt receptor fizzled protein (FZD4),Norrie disease (NDP),co-receptor low-densitylipoprotein receptor-related protein 5 (LRP5),and tetrasin 12 (TSPANI2),zinc finger protein408 (ZNF408),kinesin family member 11 (KIF11) gene.Among them,FZD4,NDP,LRPS,TSPANI2 and other four genes play an important role in the Norrin/Frizzled 4 signaling pathway.In retinal capillary endothelial cells,Norrin specifically controls the occurrence of ocular capillaries by activating the Norrin/Frizzled 4 signaling pathway.ZNT408 and KIF11 are newly discovered pathogenic genes related to FEVR in the past 5 years.ZNF408 encodes the transcription factor that plays an important role in retinal angiogenesis.KIF 11 plays a role in eye development and maintenance of retinal morphology and function.

Clinical features and identification of gene mutation in families with familial exudative vitreoretinopathy / 中华眼底病杂志

Objective To identify mutations in NDP,FZD4,LRPS,TSPAN12 in Chinese families with familial exudative vitreoretinopathy (FEVR) and observe the clinical features.Methods Retrospective case series study.The 9 patients (18 eyes) and 5 normal members from 4 unrelated families were included in the study.The patients medical history and family history were collected in detail.All patients underwent best corrected visual acuity (BCVA),slit-lamp biomicroscopy,fundus colorized photography,fundus fluorescein angiography (FFA).Genomic DNA were collected from all the patients.Mutations were detected by directly sequencing to the whole coding region and exon-intron boundaries ofNDP,FZD4,LRP5 and TSPAN12 gene.Polyphen and SWT programs were used to predict the effects on the structure and functional properties of mutant protein.Results There were two affected individuals in the family 2 carried LRP5 gene mutation [c.1330C＞T (p.R444C)] in exon 6 by sequence analysis.A score of 0.882 was acquired by Polyphen program analysis.And the missense change was predicted to be pathogenic by SIFT.Fundus changes of the proband showed angioplasia,tortuosity of peripheral vessels.And temporal dragging of the optic disc,peripheral avascular zone,neovascularization were found in FFA.Brush-like and straight of peripheral vessels were found in I 1.No variant was found in NDP,FZD4 and TSPAN12 gene.Conclusion Our study supports the gene mutation c.1330C＞T (p.R444C) of LRP5 is pathogenesis of FEVR.Patients with the same mutation could have variable phenotypic characteristics.

Genotype and clinical phenotype analysis in patients with retinitis pigmentosa and cone rod dystrophy / 中华眼底病杂志

Objective To observe the gene mutation and clinical phenotype of patients with retinitis pigmentosa (RP) and cone rod dystrophy (CORD).Methods Thirty-seven patients with RP and 6 patients with CORD and 95 family members were enrolled in the study.The patient's medical history and family history were collected.All the patients and family members received complete ophthalmic examinations to determine the phenotype,including best corrected visual acuity,slit lamp microscope,indirect ophthalmoscopy,color fundus photography,optical coherence tomography,full-field electroretinogram,and fluorescein fundus angiography.DNA was abstracted from patients and family members.Using target region capture sequencing combined with next-generation sequencing to screen the 232 candidate pathogenic mutations.Polymerase chain reaction and direct sequencing were used to confirm the pathogenic pathogenic mutations and Co-segregation is performed among members in the family to determine pathogenic mutation sites.The relationship between genotype and clinical phenotype of RP and CORD was analyzed.Results Of the 37 patients with RP,13 were from 6 families,including 4 families with autosomal dominant inheritance,2 families with autosomal recessive inheritance,and 3 in 6 families were detected pathogenic gene mutations.24 cases were scattered RP.Six patients with CORD were from four families,all of which were autosomal recessive.Of the 43 patients,21 patients were detected the pathogenic gene mutation,and the positive rate was 48.8％.Among them,15 patients with RP were detected 10 pathogenic gene mutations including USH2A,RP1,MYO7A,C8orf37,RPGR,SNRNP200,CRX,PRPF31,C2orf71,IMPDH1,and the clinical phenotype included 10 typical RP,2 cases of RPSP,3 cases of Usher syndrome type 2 and 6 cases of CORD patients were all detected pathogenic gene mutations,including 2 cases of ABCA4,2 mutations of RIMS 1 gene,1 case of CLN3 gene mutation,and 1 case of CRB 1 and RPGR double gene mutation.Conclusions RP and CORD are clinically diverse in genotype and clinically phenotypically similar.For patients with early RP and CORD,clinical phenotype combined with genetic analysis is required to determine the diagnosis of RP and CORD.

Progress and opportunities of gene and stem cell therapy on hereditary ocular fundus diseases / 中华眼底病杂志

Hereditary ocular fundus disease is an important cause of irreversible damage to patients' visual acuity.It has attracted much attention due to its poor prognosis and lack of effective clinical interventions.With the discovery of a large number of hereditary ocular fundus genes and the development of gene editing technology and stem cell technology,gene and stem cell therapy emerged as the new hope for curing such diseases.Gene therapy is more directed at early hereditary ocular fundus diseases,using wild-type gene fragments to replace mutant genes to maintain existing retinal cell viability.Stem cell therapy is more targeted at advanced hereditary ocular fundus diseases,replacing and filling the disabled retinal cell with healthy stem cells.Although gene and stem cell therapy still face many problems such as gene off-target,differentiation efficiency,cell migration and long-term efficacy,the results obtained in preclinical and clinical trials should not be underestimated.With the emergence of various new technologies and new materials,it is bound to further assist gene and stem cell therapy,bringing unlimited opportunities and possibilities for the clinical cure of hereditary ocular fundus diseases.

Analysis of BEST1 gene mutations and clinical features in multifocal vitelliform retinopathy patients / 中华眼底病杂志

Objective To analyze the BEST1 gene mutations and clinical features in patients with multifocal vitelliform retinopathy (MVR).Methods This is a retrospective case series study.Five MVR families with MVR,including 9 patients and 10 healthy family members were recruited.Clinical evaluations were performed in all MVR patients and their family members,including best-corrected visual acuity (BCVA),intraocular pressure (IOP),refraction,slit-lamp examination,90 D preset lens examination,gonioscopy,color fundus photography,optical coherence tomography (OCT),fundus autofluorescence (AF),ultrasound biomicroscopy (UBM) and axial length measurement.Electro-oculogram (EOG) was performed in 12 eyes and visual field were performed in 13 eyes.Peripheral blood samples were collected in all subjects to extract genomic DNA.Coding exons and flanking intronic regions of BEST 1 were amplified by polymerase chain reaction and analyzed by Sanger sequencing.Results Among the 5 MVR families,3 probands from three families had family history,including 1 family had autosomal dominant inheritance pattern.Two patients from 2 families were sporadic cases.Screening of BEST1 gene identified four mutations,including three missense mutations (c.140G＞T,p.R47L;c.232A＞T,p.I78F;c.698C＞T,p.P233L) and 1 deletion mutation (c.910_912del,p.D304del).Two mutations (p.R47L and p.I78F) were novel.The BCVA of affected eyes ranged from hand motion to 1.0.The mean IOP was (30.39± 11.86) mmHg (1 mmHg=0.133 kPa).The mean refractive diopter was (-0.33 ± 1.68) D.Twelve eyes had angle-closure glaucoma (ACG) and 4 eyes had angle closure (AC).EOG Arden ratio was below 1.55 in all patients.The mean anterior chamber depth was (2.17± 0.29) mm.Visual field showed defects varied from paracentral scotoma to diffuse defects.The mean axial length was (21.87± 0.63) mm.All MVR patients had multifocal vitelliform lesions in the posterior poles of retina.ACG eyes demonstrated pale optic disc with increased cup-to-disc ratio.OCT showed retinal edema,extensive serous retinal detachment and subretinal hyper-reflective deposits which had high autofluorescence in AF.The genetic testing and clinical examination were normal in 10 family members.Conclusions MVR patients harbored heterozygous mutation in the BEST1 gene.Two novel mutations (p.R47L and p.I78F) were identified.These patients had clinical features of multifocal vitelliform retinopathy and abnormal EOG.Most patients suffered from AC/ACG.

Benign familial fleck retina: multimodal imaging including optical coherence tomography angiography / Benign familial fleck retina: estudo multimodal incluindo OCT angiography

ABSTRACT This report presents multimodal imaging of a 27-year-old woman diagnosed with benign familial fleck retina (OMIM 228980), an uncommon disorder. Fundus photographs revealed retinal flecks that affected her post-equatorial retina but spared the macular area. Fundus autofluorescence and infrared imaging demonstrated a symmetrical pattern of yellow-white fleck lesions that affected both eyes. Her full-field electroretinogram and electrooculogram were normal. An optical coherence tomography B-scan was performed for both eyes, revealing increased thickness of the retinal pigmented epithelium leading to multiple small pigmented epithelium detachments. The outer retina remained intact in both eyes. Spectral-domain optical coherence tomography angiography with split-spectrum amplitude decorrelation algorithm and 3 × 3 mm structural en face optical coherence tomography did not show macular lesions. Benign familial fleck retina belongs to a heterogenous group of so-called flecked retina syndromes, and should be considered in patients with yellowish-white retinal lesions without involvement of the macula.

RESUMO O objetivo do presente relato é demonstrar um estudo multimodal de um paciente com diagnóstico de Benign Familial Fleck Retina (BFFR) (OMIM 228980), uma alteração retinana muito rara. Retinografia colorida demonstrou "flecks" na retina posterior ao equador, poupando mácula. Tanto autofluorescência quando imagem "infrared," nota-se padrão simétrico de lesões amareladas em ambos os olhos. Eletrorretinograma padrão de campo total e EOG não evidenciaram alterações. SD OCT B-scan demostrou pequenos e múltiplos descolamentos do epitélio pigmentado (EPR), com retina externa intacta em ambos os olhos. Angiografia por OCT com "split-spectrum amplitude decorrelation algorithm" e "structural" "en face" OCT 3 x 3 mm não apontaram anormalidades na mácula. BFFR pertence ao heterogêneo grupo chamado "flecked retina syndromes," devendo ser considerada em pacientes com flecks retinianos poupando mácula.

Research progress on genetics of familial exudative vitreoretinopathy / 中华实验眼科杂志

Familial exudative vitreoretinopathy (FEVR) is an inherited retinal disorder characterized by abnormal vascularization of the peripheral retina with a variety of phenotypes.Genetic analyses have identified five causative genes,including FZD4,LRP5,NDP,TSPAN12 and ZNF408,which were associated with autosomal dominant (AD),autosomal recessive and X-linked recessive FEVR.FZD4,LRP5 and TSPAN12 are key genes in classical Wnt pathway,which plays an important role in retinal angiogenesis.FZD4 encodes FZD4 protein that forms a receptor complex with LRP5 and TSPAN12.The complex binds with Wnt ligand or Norrin,encoding by NDP,to active Wnt/Norrin signaling network.ZNF408 encodes zinc finger protein,which is associated with AD FEVR.The current review provided a comprehensive summary of the genes involved in FEVR.

An association between subclinical familial exudative vitreoretinopathy and rod-cone dystrophy / Associação entre vitreorretinopatia exsudativa familiar subclínica e distrofia de cones e bastonetes

A 21-year-old Caucasian man presented with a complaint of nyctalopia. Visual acuity in both eyes was 20/20 and anterior segment biomicroscopy results were unremarkable. Fundoscopy revealed peripheral avascular zones, minimal peripheral retinal exudation from the retinal vessels, peripheral retinal telangiectasias and anastomosis in both eyes, and retinal vascular dragging toward the temporal periphery in both eyes. Full field electroretinography showed that rod responses were almost absent and that cone responses were reduced. Macular optical coherence tomography showed normal structure in both eyes. Vascular changes were attributed to a subclinical form of familial exudative vitreoretinopathy. This was an interesting case due to the association of familial exudative vitreoretinopathy with rod-cone dystrophy.

Um homem caucasiano de 21 anos foi avaliado com queixa de nictalopia. A acuidade visual era 20/20 em ambos os olhos. Biomicroscopia do segmento anterior era normal. A fundoscopia revelava zonas avasculares periféricas, exsudação mínima dos vasos retinianos periféricos da retina, telangiectasias da retina periférica com anastomoses em ambos os olhos e deslocamento vascular da retina em direção a periferia temporal em ambos os olhos. O eletrorretinograma (ERG) de campo total apresentava respostas de bastonetes praticamente indetectáveis e redução das respostas de cones. A tomografia de coerência óptica (OCT) macular mostrava estrutura normal em AO. As alterações vasculares foram atribuídas à forma subclínica da vitreorretinopatia exsudativa familiar. Este é um caso interessante com a associação de vitreoretinopatia exsudativa familiar e distrofia de cones e bastonetes (RCD).

Progress in mechanism of CYP4V2 gene mutations for Bietti crystalline corneoretinal dystrophy / 中华实验眼科杂志

Bietti crystalline corneoretinal dystrophy (BCD) is a common form of hereditary retinal degeneration in Chinese.Mutation of the cytochrome P450 4V2 (CYP4V2) gene,a novel family member of the cytochrome P450 genes on chromosome 4q35,has been identified in BCD patients,with the common mutation locus at c.802-8 _ 810dell7insGC (Exon7del),c.992A ＞ C (p.H331 P) and c.1091-2A ＞ G (Exon 9del).CYP4V2 is responsible for oxidation of various substrates in the metabolic pathway,especially ω-hydroxylase activity towards ω-3 polyunsaturated fatty acids (PUFAs).CYP4V2 appears to be the only CYP4 memeber at significant levels in retinal cells,and it may be a prominent contributor to local metabolism of PUFAs,mainly DHA (C22:6n-3),in retinal cells.To understand and investigate the main mechanism of CYP4V2 gene mutation causing BCD is important in the study of genetic diagnosis and genetic management of BCD.This review summarized the current advance in the genetic mechanism of BCD and function of CYP4V2 gene,elucidated the substrate specificity and unraveled the biochemical pathways that may impact function of CYP4V2 in BCD patients.

Síndrome de Lujan-Fryns: recorrência familiar na mesma geração / Lujan-Fryns syndrome: familial recurrence in the same generation

Objetivos: relatar casos da Síndrome de Lujan-Fryns em dois irmãos.Descrição dos casos: Paciente 1 ? sexo masculino, 18 anos, apresentando alta estatura, hiperextensibilidade articular, região frontal proeminente, face longa e estreita, hipoplasia do maxilar, mandíbula pequena, nariz largo com ponte nasal alta e estreita, filtro curto e profundo, lábio superior fino e palato arqueado, voz hipernasal e hipotonia generalizada. Instabilidade emocional, distúrbio de aprendizagem, timidez e fobia social. Prolapso de válvula mitral com refluxo discreto e ectasia da raiz da aorta Miopia, sem retinopatia. Resultados normais para cariótipo em sangue periférico com banda G, análise molecular para X frágil e investigação para homocistinúria. Paciente 2 ? sexo feminino,22 anos, apresenta quadro clínico semelhante ao paciente 1 (seu irmão), porém de intensidade mais leve. Exames complementares sem alterações significativas.Conclusões: os pacientes apresentam aspecto marfanóide e retardo mental compatível com herança ligada ao X. Apesar de ainda não ter sido realizada a pesquisa da mutação no gene MED 12, o diagnóstico clínico de Síndrome de Lujan-Fryns está respaldado pela literatura. Não existe tratamento específico e os pacientes requerem educação especial e acompanhamento psicológico.

Aims: To report cases of Lujan-Fryns syndrome in two siblings.Description of cases: Patient 1 ? male, 16 years, presented high stature, hiperextensibility of joints, prominent forehead, long face and narrow, maxillary hypoplasia, small jaw, large nose with high and narrow nasal bridge and short and deep filter, thin upper lip and arched palate, hypernasal voice and generalized hypotonia. Lability, learning disabilities, timidity and social phobia. Mitral valve prolapse with slight reflux and dilatation of the aortic root. Myopia without retinopathy. Karyotype in peripheral blood with G-band, molecular analysis for fragile X and biochemical investigation for homocystinuria had normal results. Patient 2 ? female, 19 years, presented clinical symptoms similar to the patient 1 (her brother), although milder. Complementary tests showed no significant changes.Conclusions: These patients present marfanoid aspect and mental retardation consistent with X-linked inheritance. Although no research has been carried out on mutation in the gene MED 12, the clinical diagnosis of Lujan-Fryns syndrome is supported by the literature. There is no specific treatment, and the patients require special education and psychological counseling.

Manuseio anestésico de paciente portador de telangiectasia hemorrágica hereditária (síndrome de Rendu-Osler-Weber): relato de caso / Manoseo anestésico de paciente portador de telangiectasia hemorrágica hereditaria (síndrome de Rendu - Osler - Weber): relato de caso / Anesthetic management of a patient with hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber syndrome): case report

JUSTIFICATIVA E OBJETIVOS: A telangiectasia hemorrágica hereditária (THH), também conhecida como síndrome de Rendu-Osler-Weber, é uma doença autossômica dominante, caracterizada por displasia vascular mucocutânea e visceral associada a episódios freqüentes de epistaxe e sangramentos gastrintestinais. O objetivo do presente relato foi descrever a anestesia em paciente portador dessa síndrome. RELATO DO CASO: Paciente do sexo masculino, 25 anos, submetido à correção cirúrgica de fratura de órbita esquerda. Portador da tríade epistaxe recorrente, histórico familiar e telangectasia, apresentava diagnóstico de THH. Durante a investigação pré-operatória não foram encontradas malformações vasculares pulmonares, encefálicas ou do trato gastrintestinal. O paciente foi submetido à anestesia venosa total, uma hora após a administração profilática de antifibrinolítico. O sangramento foi considerado normal para a operação proposta e não houve instabilidade hemodinâmica ou necessidade de transfusão sanguínea perioperatória. A extubação ocorreu na sala cirúrgica e o paciente foi liberado para o quarto após 60 minutos e a alta hospitalar foi após 24 horas. CONCLUSÕES: A THH é uma doença autossômica dominante que provoca displasia vascular musculocutânea e visceral. Pode haver perda sanguínea perioperatória acima da esperada para pacientes portadores dessa síndrome. Como o sangramento não é resultado de defeito na cascata de coagulação mas da exposição cirúrgica da estrutura vascular malformada, a conduta perioperatória inclui o emprego de antifibrinolíticos, a realização de hemostasia adequada e da hipotensão arterial induzida, quando não houver contra-indicação. A avaliação pré-anestésica deve incluir a pesquisa de malformações vasculares encefálicas, pulmonares ou do trato gastrintestinal.

JUSTIFICATIVA Y OBJETIVOS: La telangiectasia hemorrágica hereditaria (THH), también conocida como síndrome de Rendu-Osler-Weber, es una enfermedad autosómica dominante, caracterizada por displasia vascular muco-cutánea y visceral asociada a frecuentes episodios de epistaxis y sangramientos gastrointestinales. El objetivo del presente relato fue el de describir la anestesia en paciente portador de ese síndrome. RELATO DEL CASO: Paciente del sexo masculino, 25 años, sometido a la corrección quirúrgica de fractura de órbita izquierda. Portador de la tríade epistaxis recurrente, historial familiar y telangiectasia presentaba diagnóstico de THH. Durante la investigación preoperatoria no se encontraron malformaciones vasculares pulmonares, encefálicas o del tracto gastrointestinal. El paciente se sometió a la anestesia venosa total, una hora después de la administración profiláctica de antifibrinolítico. El sangramiento fue considerado normal para la operación propuesta, y no hubo inestabilidad hemodinámica o necesidad de transfusión sanguínea perioperatoria. La extubación fue hecha en la sala de cirugía, y el paciente fue enviado a la habitación 60 minutos después. El alta fue en 24 horas. CONCLUSIONES: La THH es una enfermedad autosómica dominante, caracterizada por displasia vascular muco-cutánea y visceral. Puede haber pérdida sanguínea perioperatoria por encima de la esperada para pacientes portadores de ese síndrome. Como el sangramiento no es resultado de un defecto en la cascada de coagulación, sino de la exposición quirúrgica de la estructura vascular malformada, la conducta perioperatoria incluye el uso de antifibrinolíticos, la realización de una hemostasis adecuada y la hipotensión arterial inducida, cuando no haya contraindicación. La evaluación preanestésica debe incluir la investigación de malformaciones vasculares encefálicas, pulmonares o del tracto gastrointestinal.

BACKGROUND AND OBJECTIVES: Hereditary hemorrhagic telangiectasia (HHT), also known as Rendu-Osler-Weber syndrome, is an autosomal dominant disorder characterized by mucocutaneous and visceral vascular dysplasia associated with frequent episodes of epistaxis and gastrointestinal bleeding. The objective of this report was to describe the anesthesia of a patient with this syndrome. CASE REPORT: A 25 years old male patient underwent surgical correction of an orbital fracture. He had the triad of recurrent epistaxis, family history, and telangiectasia, and had been diagnosed with HHT. Pulmonary, brain, or gastrointestinal tract vascular malformations were not detected in the preoperative investigation. The patient underwent total venous anesthesia one hour after the administration of an antifibrinolytic drug. Bleeding was considered normal for this type of surgery, and hemodynamic instability or the need of perioperative blood transfusion was not detected. The patient was extubated in the operating room; he was transferred to the room after 60 minutes and discharged from the hospital after 24 hours. CONCLUSIONS: Hereditary hemorrhagic telangiectasia is an autosomal dominant disorder that leads to mucocutaneous and visceral vascular dysplasia. Perioperative blood loss can be greater than expected in patients with this syndrome. Since bleeding does not result from a defect in the coagulation cascade but from the surgical exposure of malformed vascular structures, perioperative conduct includes the use of antifibrinolytics, adequate homeostasis, and induced hypotension in the absence of contraindications. Pre-anesthetic evaluation should include the search for brain, lung, and gastrointestinal vascular malformation.

New primary mutation of mtDNA in Leber′s hereditary optic neuropathy / 中华眼底病杂志

Objective To analyze the new primary mutation in Chinese people with Leber′s hereditary optic neuropathy (LHON). Methods Genomic DNA was collected from 260 suspected LHON patients and 100 normal healthy persons. The mitochondria DNA mutation at nucleotide position (NP) 15257 and the hot spot (14452-14601 bp) of ND6 gene which include the mutations at NP (14482, 14498, 14568, 14596, 14495, and 14459) were screened by using polymerase chain reaction (PCR), heteroduplex-single strand conformation polymorphism (HA-SSCP) and restriction fragment length polymorphism (RFLP) analysis and sequencing. Primary mutation spectrum of Chinese race was analyzed. Results Eight kinds of polymorphism of mitochondria DNA were found in 260 suspected LHON patients and 100 normal healthy persons, including NP 14488C, 14518G, and 14617G which hadn't been reported (http://www.mitomap.org/). No mutation at NP 15257, 14482, 14498, 14568, 14596, 14495, and 14459 was found. Conclusion The NP 15257A may not be the primary mutation in Chinese. Because of the race difference, 14452-14601 bp in ND6 gene may not be the hot spot in Chinese patients with LHON, and other hot spots may exist.