Resumen La displasia ectodérmica hipohidrótica (DEH) es una genodermatosis caracterizada por afectación de la piel y sus anexos. Su prevalencia se aproxima a 1/5000 recién nacidos en el mundo. Presenta heterogeneidad de locus por lo que su herencia puede ser: autosómica dominante (HAD), autosómica recesiva (HAR) y recesiva ligada al cromosoma X (RLX). Puede detectarse en etapa prenatal, pero en general el diagnóstico se realiza en la primera infancia. La DEH leve se ve en mujeres portadoras de una mutación en el gen EDA (Xq12-13.1). Su expresividad es variable, pero puede llegar a tener gran repercusión bio-psico-social. El tratamiento se define como paliativo, con el uso de cremas hidratantes, control ambiental, prótesis dentales. Un trabajo sobre gemelares diagnosticados en período prenatal y tratados con una enzima sintética intrautero abre gran expectativa sobre la posibilidad de la terapia enzimática o génica. Presentamos el caso de una niña de 4 años con oligodoncia y afectación leve de piel que cuenta con antecedentes familiares por línea materna descriptos como eczema y dermatitis atópica, en la cual se realizó estudio genético que identificó una variante probablemente patogénica en el gen EDA. Para definir la patogenicidad de esta variante, se plantea analizar la segregación en la familia materna, junto con la profundización del análisis fenotípico en estos familiares.

Abstract Hypohydrotic ectodermal dysplasia (HDE) is a genodermatosis characterised by involvement of the skin and its annexes. Its prevalence is close to 1/5.000 newborns in the world. It presents heterogeneity of locus so its inheritance mechanism can be autosomal dominant (ADI), autosomal recessive (ARI) and recessive linked to the X chromosome (RLX). It can be detected at the prenatal stage, but in general the diagnosis is made in early childhood. Mild HDE is seen in women with a mutation in the EDA gene (Xq12-13.1). Its expressiveness is variable, but it can have a great bio-psycho-social impact. The treatment is defined as palliative, with the use of moisturisers, environmental control, dental prostheses. A work on twins diagnosed in the prenatal period and treated with an intrauterous synthetic enzyme opens great expectation about the possibility of enzymatic or gene therapy. We present the case of a 4-year-old girl with oligodontia and mild skin involvement who has a family history described as eczema and atopic dermatitis, in which a genetic study was carried out that identified a probably pathogenic variant in the EDA gene. To define the pathogenicity of this variant, it is proposed to analyse the segregation in the maternal family, along with the deepening of the phenotypic analysis in these family members.

Resumo A displasia ectodérmica hipo-hidrótica (DEH) é uma genodermatose caracterizada pelo envolvimento da pele e seus anexos. Sua prevalência se aproxima de 1/5000 recém-nascidos no mundo. Apresenta heterogeneidade de locus pelo que sua herança pode ser: autossômica dominante (HAD), autossômica recessiva (HAR) e recessiva ligada ao cromossomo X (RLX). Pode ser detectado na fase pré-natal, mas em geral o diagnóstico é feito na primeira infância. A DEH leve é vista em mulheres portadoras de uma mutação no gene EDA (Xq12-13.1). Sua expressividade é variável, mas pode ter grande repercussão bio-psico-social. O tratamento é definido como paliativo, com o uso de cremes hidratantes, controle ambiental, próteses dentárias. Um trabalho sobre gêmeos diagnosticados no período pré-natal e tratados com uma enzima sintética intrauterino abre grande expectativa sobre a possibilidade da terapia enzimática ou gênica. Apresentamos o caso de uma menina de 4 anos com oligodontia e comprometimento leve da pele que tem antecedentes familiares por linha materna descrito como eczema e dermatite atópica, na qual foi realizado um estudo genético que identificou uma variante provavelmente patogênica no gene EDA. Para definir a patogenicidade desta variante, propõe-se analisar a segregação na família materna, juntamente com o aprofundamento da análise fenotípica nesses familiares.

ABSTRACT: Hops (Humulus lupulus L.) are of particular economic importance in the highlands of the state of Santa Catarina, Brazil, by virtue of the number of breweries in the region. However, since the cultivars currently available in the country present poor qualitative attributes and low cone productivity, there is considerable demand for improved genotypes. The results of diallel crossing experiments help to increase our understanding of inheritance processes and the mechanisms controlling the transfer of alleles with additive or non-additive action, thereby allowing breeders to explore the benefits of heterosis. The present study evaluated the general and specific combining abilities (GCA and SCA, respectively) of four hop genotypes and to obtain F1 hybrids with agronomic traits superior to those of the parents and the ability to adapt to the environmental conditions in the Santa Catarina highlands. Partial diallel crosses were performed using a randomized complete block design involving 14 treatments, namely two male parents (Cascade and Hallertauer), four female parents (Columbus, Chinook, Cascade and Hallertauer) and eight hybrid combinations, with three repetitions each. The results showed that SCA was the predominant controlling mechanism for the manifestation in hybrids of the traits length of the lateral branch, height of insertion of the first cone, plant green mass and cone productivity. Some parental combinations also exhibited high GCA, indicating the presence of favorable alleles with additive action. The best combination was Hallertauer × Cascade, a finding that highlights the importance of choosing parents from different gene pools (American × European) to obtain genetically enhanced hybrids. ABSTRACT Humulus L. L Brazil region However productivity nonadditive non action heterosis GCA respectively F 1 treatments Hallertauer, , Columbus, Columbus (Columbus Chinook each branch American European

RESUMO: O lúpulo (Humulus lupulus L.) possui grande importância econômica no planalto serrano do estado de Santa Catarina, uma vez que existem inúmeras cervejarias nesta região do Brasil. Como as cultivares disponíveis no país carecem de bons atributos qualitativos e apresentam baixa produtividade de cones, existe grande demanda por genótipos melhorados. Os resultados de experimentos de cruzamento dialélico aumentam a compreensão dos processos de herança e dos mecanismos de controle associados à transferência de alelos com ação aditiva ou não aditiva, permitindo assim que os geneticistas explorem os benefícios da heterose. Os objetivos deste estudo foram avaliar as capacidades de combinação geral e específica (CGC e CEC, respectivamente) de quatro genótipos de lúpulo e obter híbridos F1 com características agronômicas superiores às dos genitores e habilidade para se adaptar às condições ambientais do planalto catarinense. Os cruzamentos dialélicos parciais foram realizados em delineamento de blocos casualizados envolvendo 14 tratamentos, i.e. dois genitores masculinos (Cascade e Hallertauer), quatro genitores femininos (Columbus, Chinook, Cascade e Hallertauer) e oito combinações híbridas, com três repetições cada. Os resultados mostraram que a CEC dos genitores foi o mecanismo de controle predominante para a manifestação nos híbridos das características comprimento do ramo lateral, altura de inserção do primeiro cone, massa verde da planta e produtividade de cones. Algumas combinações entre genitores também manifestaram CGC elevada, indicando a presença de alelos favoráveis com ação aditiva. A melhor combinação foi Hallertauer × Cascade e essa descoberta demonstra a importância da escolha de genitores originários de diferentes grupos genéticos (Americano × Europeu) para obter híbridos geneticamente melhorados. RESUMO Humulus L. L Catarina Brasil cones melhorados heterose respectivamente F catarinense 1 tratamentos ie i i.e Hallertauer, , Columbus, Columbus (Columbus Chinook híbridas cada lateral cone elevada Americano Europeu

ABSTRACT Common bacterial blight (CBB), caused by Xanthomonas axonopodis pv. phaseoli, is the main bacterial disease affecting the production of beans (Phaseolus vulgaris L.), with significant impacts on Brazilian agriculture. The search for resistant genotypes is a fundamental strategy, given the prevalence and persistence of the pathogen in tropical conditions. Therefore, this study aimed to identify candidate genes for resistance to CBB through association mapping studies, using 126 Middle-American bean genotypes from the germplasm bank of the Instituto de Desenvolvimento Rural do Paraná. A randomized block design with four replications was used. The inoculation method was by cutting the leaves with scissors, using the isolate Xap-139y at a concentration of 107 CFU·mL-1, and the variables final score and area under the disease progress curve (AUDPC) were evaluated. The expected performance of the means and the genetic parameters were estimated using the Selegen software. The GEN203 genotype was considered resistant for AUDPC and final score. Using multi-locus models (FASTmrMLM, ISIS-EM-BLASSO, mrMLM, pLARmEB), we identified 11 quantitative trait nucleotides associated with CBB resistance and 48 candidate genes in the resistance response. These genes act in several metabolic pathways, suggesting a complex polygenic inheritance. This work contributes significantly to understanding the genetic basis of resistance to CBB and the development of bean cultivars with better adaptability and productivity in regions affected by the disease. CBB, , (CBB) pv phaseoli Phaseolus L., L L. L.) agriculture strategy conditions Therefore studies 12 MiddleAmerican Middle American Paraná used scissors Xap139y Xapy Xap 139y y 10 CFU·mL1, CFUmL1 CFUmL CFU·mL 1, CFU mL 1 CFU·mL-1 (AUDPC evaluated software GEN GEN20 multilocus multi locus FASTmrMLM, FASTmrMLM (FASTmrMLM ISISEMBLASSO, ISISEMBLASSO ISIS EM BLASSO, BLASSO ISIS-EM-BLASSO mrMLM pLARmEB, pLARmEB pLARmEB) 4 response pathways inheritance (CBB mL1 CFU·mL1 CFU·mL- GEN2

Abstract Hailey-Hailey disease is a rare genodermatosis described in 1939, with an autosomal dominant inheritance pattern, characterized by compromised adhesion between epidermal keratinocytes. It has an estimated prevalence of 1/50,000, with no gender or race predilection. It results from a heterozygous mutation in the ATP2C1 gene, which encodes the transmembrane protein hSPA1C, present in all tissues, with preferential expression in keratinocytes. Mutations in the ATP2C1 gene cause changes in the synthesis of junctional proteins, leading to acantholysis. It usually begins in adulthood, with isolated cases at the extremes of life. It manifests as vesico-bullous lesions mainly in the flexural areas, which develop into erosions and crusts. Chronic lesions may form vegetative or verrucous plaques. Pruritus, a burning feeling and pain are common. It evolves with periods of remission and exacerbation, generally triggered by humidity, friction, heat, trauma and secondary infections. The diagnosis is based on clinical and histopathological criteria: marked suprabasal acantholysis, loosely joined keratinocytes, giving the appearance of a “dilapidated brick wall”, with a few dyskeratotic cells. The acantholysis affects the epidermis and spares the adnexal epithelia, which helps in the differential diagnosis with pemphigus vulgaris. Direct immunofluorescence is negative. The main differential diagnoses are Darier disease, pemphigus vegetans, intertrigo, contact dermatitis, and inverse psoriasis. There is no cure and the treatment is challenging, including measures to control heat, sweat and friction, topical medications (corticosteroids, calcineurin inhibitors, antibiotics), systemic medications (antibiotics, corticosteroids, immunosuppressants, retinoids and immunobiologicals) and procedures such as botulinum toxin, laser and surgery. There is a lack of controlled clinical trials to support the choice of the best treatment. HaileyHailey Hailey 1939 pattern keratinocytes 150000 1 50 000 1/50,000 predilection ATPC ATP C ATP2C hSPA1C hSPAC hSPA tissues proteins adulthood life vesicobullous vesico bullous areas crusts plaques Pruritus common exacerbation humidity friction heat infections criteria dilapidated wall, wall , wall” cells epithelia vulgaris negative vegetans intertrigo dermatitis psoriasis challenging corticosteroids (corticosteroids inhibitors antibiotics, antibiotics antibiotics) (antibiotics immunosuppressants immunobiologicals toxin surgery 193 15000 5 00 1/50,00 19 1500 0 1/50,0 150 1/50, 15 1/50 1/5 1/

RESUMEN Introducción: la incontinencia pigmenti es una enfermedad genética neurocutánea de baja frecuencia con expresividad variable y un patrón de herencia dominante ligada al cromosoma X que se presenta casi exclusivamente en féminas y que se considera un gen letal en varones hemicigóticos para el cromosoma X. Se caracteriza por lesiones cutáneas presentes al nacimiento que evolucionan en diferentes estadios y puede estar asociado a otras alteraciones como las neurológicas y las oculares. Información del paciente: paciente femenina de dos años de edad que desde el nacimiento fue remitida a la Consulta de Genodermatosis por lesiones en forma de líneas pigmentadas por todo el cuerpo que solo respetaban la cara, con buen desarrollo psicomotor, sin otras manifestaciones clínicas. Conclusiones: realizar un diagnóstico precoz con un seguimiento multidisciplinario facilita la detección de complicaciones que pudieran aparecen en otros sistemas asociadas a esta enfermedad. Las acciones terapéuticas preventivas oportunas son indispensables para un pronóstico favorable en la evolución del paciente y permiten un adecuado asesoramiento genético a la familia.

ABSTRACT Introduction: Incontinence pigmenti is a low-frequency neurocutaneous genetic disease with variable expressivity and a dominant inheritance pattern linked to the X chromosome, occurring almost exclusively in females, and is considered a lethal gene in males hemizygous for the skin lesions present at birth that evolve in different stages, and may be associated with other alterations such as neurological and ocular disorders. Patient information: Two-year-old female patient, who from birth was referred to the Genodermatosis clinic for lesions in the form of pigmented lines all over the body that only spared the face, with good psychomotor development, without other clinical manifestations. Conclusions: Making an early diagnosis with multidisciplinary follow-up facilitates the detection of complications that could appear in other systems associated with this disease. Carry out timely preventive therapeutic actions; They are essential for a favorable prognosis in the patient's evolution, allowing adequate genetic counseling for the family.

Abstract Renal involvement is one of the most severe morbidities of Fabry disease (FD), a multisystemic lysosomal storage disease with an X-linked inheritance pattern. It results from pathogenic variants in the GLA gene (Xq22.2), which encodes the production of alpha-galactosidase A (α-Gal), responsible for glycosphingolipid metabolism. Insufficient activity of this lysosomal enzyme generates deposits of unprocessed intermediate substrates, especially globotriaosylceramide (Gb3) and derivatives, triggering cellular injury and subsequently, multiple organ dysfunction, including chronic nephropathy. Kidney injury in FD is classically attributed to Gb3 deposits in renal cells, with podocytes being the main target of the pathological process, in which structural and functional alterations are established early and severely. This configures a typical hereditary metabolic podocytopathy, whose clinical manifestations are proteinuria and progressive renal failure. Although late clinical outcomes and morphological changes are well established in this nephropathy, the molecular mechanisms that trigger and accelerate podocyte injury have not yet been fully elucidated. Podocytes are highly specialized and differentiated cells that cover the outer surface of glomerular capillaries, playing a crucial role in preserving the structure and function of the glomerular filtration barrier. They are frequent targets of injury in many nephropathies. Furthermore, dysfunction and depletion of glomerular podocytes are essential events implicated in the pathogenesis of chronic kidney disease progression. We will review the biology of podocytes and their crucial role in regulating the glomerular filtration barrier, analyzing the main pathogenic pathways involved in podocyte injury, especially related to FD nephropathy. FD, , (FD) Xlinked X linked pattern Xq22.2, Xq222 Xq Xq22.2 Xq22 2 (Xq22.2) alphagalactosidase alpha galactosidase αGal, αGal α Gal (α-Gal) metabolism substrates Gb (Gb3 derivatives subsequently nephropathy process severely podocytopathy failure elucidated capillaries barrier nephropathies Furthermore progression (FD Xq22. Xq2 (Xq22.2 (α-Gal (Gb (Xq22. (Xq22 (Xq2 (Xq

Resumo O acometimento renal é uma das mais severas morbidades da doença de Fabry (DF), enfermidade multissistêmica de depósito lisossômico com padrão de herança ligada ao cromossomo X, decorrente de variantes patogênicas do gene GLA (Xq22.2), que codifica a produção de alfa-galactosidase A (α-Gal), responsável pelo metabolismo de glicoesfingolipídeos. A atividade insuficiente dessa enzima lisossômica gera depósitos de substratos intermediários não processados, especialmente do globotriaosilceramida (Gb3) e derivados, desencadeando injúria celular e, posteriormente, disfunção de múltiplos órgãos, incluindo a nefropatia crônica. A lesão renal na DF é classicamente atribuída aos depósitos de Gb3 nas células renais, sendo os podócitos o alvo principal do processo patológico, nos quais as alterações estruturais e funcionais são instaladas de forma precoce e severa, configurando uma podocitopatia metabólica hereditária típica, cujas manifestações clínicas são proteinúria e falência renal progressiva. Embora os desfechos clínicos tardios e as alterações morfológicas estejam bem estabelecidos nessa nefropatia, os mecanismos moleculares que deflagram e aceleram a injúria podocitária ainda não estão completamente elucidados. Podócitos são células altamente especializadas e diferenciadas que revestem a superfície externa dos capilares glomerulares, desempenhando papel essencial na preservação da estrutura e função da barreira de filtração glomerular, sendo alvos frequentes de injúria em muitas nefropatias. A disfunção e depleção dos podócitos glomerulares são, além disso, eventos cruciais implicados na patogênese da progressão da doença renal crônica. Revisaremos a biologia dos podócitos e seu papel na regulação da barreira de filtração glomerular, analisando as principais vias patogênicas envolvidas na lesão podocitária, especialmente relacionadas à nefropatia da DF. DF, , (DF) X Xq22.2, Xq222 Xq Xq22.2 Xq22 2 (Xq22.2) alfagalactosidase alfa galactosidase αGal, αGal α Gal (α-Gal) glicoesfingolipídeos processados Gb (Gb3 derivados posteriormente órgãos crônica renais patológico severa típica progressiva elucidados glomerular nefropatias disso (DF Xq22. Xq2 (Xq22.2 (α-Gal (Gb (Xq22. (Xq22 (Xq2 (Xq

ABSTRACT The assembly of cayenne pepper (Capsicum frutescens L.) cannot be separated from the direction of qualitative character development. This is based on the role of qualitative characters in determining nutritional content and market segments. Therefore, the analysis of qualitative characters in the F4 multiple cross cayenne pepper population needs to be done in determining the direction of line development in the next generation. The purpose of this study was to identify the inheritance pattern of qualitative traits and genotype grouping from a population of F4 multiple cross lines. The research was conducted at the Experimental Field of Hasanuddin University, Makassar, Indonesia. The study was designed with the concept of observation on 90 F4 multiple cross chili lines and three parental cultivars (Dewata F1, Bara and Ungara). Observations focused on 10 qualitative characters. The analysis showed that there are two types of diversity in this population, namely centralized diversity and distributed diversity. Centralized diversity consists of leaf color, book color, leaf shape, canopy density, stem color, fruit shape, and fruit tip shape. In contrast, characters that have a diverse distribution are crown color, young and old chili fruit color. The distribution results show three main groups, namely the Dewata-Bara group (27 genotypes), the Ungara group (16 genotypes) and the rest are groups outside of these two groups. Based on the whole study, the results of this evaluation are recommended as a consideration for the selection of F5 lines in supporting the direction of releasing chili cultivars from multiple cross.

Resumen La poliposis adenomatosa familiar (PAF) es un síndrome hereditario autosómico dominante. Aunque la principal manifestación de esta enfermedad es la presencia de numerosos adenomas de colon, también ocurre afectación del tracto gastrointestinal superior. Se presenta un reporte de una paciente joven con una poliposis gástrica (más de 100 pólipos). Se realiza una breve revisión actualizada del tema enfocada en los hallazgos endoscópicos, así como sugerencias actualizadas en el manejo y seguimiento de los pólipos gástricos en la PAF.

Abstract Familial adenomatous polyposis (FAP) is an autosomal dominant inheritance syndrome. Although the main manifestation of this disease is the presence of numerous colon adenomas, upper gastrointestinal tract involvement also occurs. A report of a young patient with gastric polyposis (more than 100 polyps) was presented. There was a brief updated review of the topic focused on endoscopic findings, including updated suggestions on gastric polyps in FAP management and monitoring.

Resumo O presente trabalho tem por objetivo investigar a extensão da liberdade para testar no ordenamento jurídico inglês, visando aferir como as recentes decisões judiciais vêm impactando na autonomia privada do testador para dispor de seus bens para depois da morte. Para tanto, faz-se uso do método dedutivo, apoiado na revisão bibliográfica, com análise da legislação, da doutrina e da jurisprudência. A hipótese aventada é a de que a atual legislação inglesa, que possibilita a revisão das disposições de última vontade do falecido pelo Poder Judiciário sem a fixação de parâmetros objetivos mínimos para o direcionamento do julgador nos casos em que há contestação do testamento por parte dos legitimados para requererem uma provisão familiar, pode causar grande insegurança jurídica aos jurisdicionados, além de representar verdadeira afronta ao princípio da autonomia privada. Ao final, concluiu-se que é necessário o estabelecimento de critérios objetivos mínimos na Lei de herança inglesa, que deverão ser observados pelo Poder Judiciário para fins de mínima padronização dessas decisões, visando, assim, promover o esperado equilíbrio entre a autonomia privada do testador e a proteção de seus dependentes. A conclusão apresentada, em nada contraria o sistema jurídico vigente na Inglaterra, na medida em que, diante da complexidade das situações jurídicas que se apresentam na contemporaneidade, houve uma verdadeira aproximação entre os sistemas de common law e civil law, de maneira que não se vislumbram mais sistemas puros, sendo necessária uma complementação entre eles para fins de promoção de justiça.

Abstract The aim of this paper is to investigate the extent of freedom to testify in the English legal system, with a view to assessing how recent court decisions have impacted on the testator's private autonomy to dispose of their assets after death. To this end, the deductive method is used, based on a literature review, analyzing legislation, doctrine, and case law. The hypothesis put forward is that the current English legislation, which makes it possible for the Judiciary to review the deceased's last will and testament without setting minimum objective parameters to guide the judge in cases where the will is contested by those entitled to apply for family provision, can cause great legal uncertainty for the courts, as well as representing a real affront to the principle of private autonomy. In the end, we conclude that it is necessary to establish minimum objective criteria in English inheritance law, which should be observed by the Judiciary for the purposes of minimum standardization of these decisions, thus aiming to promote the expected balance between the private autonomy of the testator and the protection of his/her dependents. This conclusion does not, in any way, contradict the legal system in force in England, insofar as, given the complexity of the legal situations that arise in contemporary times, there has been a real rapprochement between the common law and civil law systems, so that pure systems are no longer visible, and it is necessary to complement them in order to promote justice.

Counterabstract This writing was born without a summary, without the need to reduce in lines what the conditions of possibility of history and contingency provoke. This dissertation presented by Miguel Morey comes from loud disputes, betting on historicity, contradiction and chance, where Zarathustra’s gesture shows that, since there is no origin, only the incessant provenance that occurs between knowledge and knowing, they propose a historical meaning, never given but open to the future. In these lines, Nietzsche’s untimely ideas enter the scene, to remind us that what is given is always to come, in a challenge that will never cease against universals, assuming the differences between the real and the rational that never end up converging, and where in turn the historical a priori dictates or justifies the inheritance to his heirs. Thus, the Nietzschean contingency that is presented in these lines is the gesture of a thought that is put into work and action incessantly, blurring itself in the multiplicity and heterogeneity of the registers noisily and silently, playing between the eternal return, where each repetition opens the possibility of instability and event, between unfoldings and overflows of meanings, which reminds us that we are contingent, finite, uncertain and fragmentary beings...unstable between lack and the future.

Contraresumen Este escrito nació sin resumen, sin necesidad de reducir en líneas lo que las condiciones de posibilidad de la historia y la contingencia provocan. Esta disertación presentada por Miguel Morey procede de disputas en voz alta, apostando a la historicidad, a la contradicción y el azar, donde el gesto de Zaratustra evidencia que, al no haber origen, solo la procedencia incesante que se produce entre el saber y el conocer, proponen un sentido histórico, nunca dado sino abierto al porvenir. En estas líneas, las intempestivas de Nietzsche entran en la escena, para recordarnos que lo dado, está siempre por venir, en una impugnación que no cesará nunca contra los universales, asumiendo las diferencias entre lo real y lo racional que no terminan nunca por converger, y donde a su vez el apriori histórico dictamina ni justifica la herencia a sus herederos. Así la contingencia nietzscheana que se presenta en estas líneas, es el gesto de un pensamiento que se pone en obra y acción incesantemente, difuminándose en la multiplicidad y heterogeneidad de los registros ruidosa y silenciosamente, jugándose entre el eterno retorno, donde cada repetición abre la posibilidad a la inestabilidad y al acontecimiento, entre desdoblamientos y desbordamientos de sentidos, que nos recuerda que somos seres contingentes, finitos, inciertos y fragmentarios…inestables entre la falta y el porvenir.

Resumen Introducción: El síndrome de Miller-Dieker cuenta con un patrón de herencia autosómico dominante y pertenece al grupo de trastornos de la migración neuronal. Se caracteriza por la presencia de lisencefalia de tipo 1, retraso global del desarrollo, microcefalia, epilepsia y dismorfismos faciales dados por mutaciones en el cromosoma 17p13. El síndrome de Miller-Dieker es una enfermedad extremadamente rara con prevalencia de 1 caso por cada 100,000 recién nacidos vivos. Presentación de casos: Nosotros presentamos dos casos de síndrome de Miller-Dieker en los que datos de la exploración física y del interrogatorio fueron pistas que permitieron una fuerte sospecha diagnóstica y que a su vez el diagnóstico definitivo mediante FISH permitió brindar un adecuado manejo con la finalidad de mejorar el pronóstico a largo plazo. Conclusión: Se debe tener una alta sospecha diagnóstica mediante la exploración física dirigida a identificar alteraciones en pacientes con epilepsia de difícil control, ya que permite guiar el diagnóstico etiológico y con ello brindar un adecuado tratamiento.

Abstract Introduction: Miller-Dieker syndrome has an autosomal dominant pattern of inheritance and belongs to the group of neuronal migration disorders. It is characterized by the presence of type 1 lissencephaly, global development delay, microcephaly, epilepsy and facial dysmorphisms caused by mutations in chromosome 17p13. Miller-Dieker syndrome is an extremely rare disease with a prevalence of 1 case per 100,000 live births. Case presentation: We present two cases of Miller-Dieker syndrome in which data from the physical examination and questioning were clues that allowed a strong diagnostic suspicion and that, in turn, the definitive diagnosis by means of FISH allowed us to provide adequate management in order to improve the long-term prognosis. Conclusion: A high diagnostic suspicion must be achieved through physical examination aimed at identifying alterations in patients with difficult-to-control epilepsy, since it allows guiding the etiological diagnosis and thereby providing adequate treatment.

Resumen Introducción: La pigmentación de las papilas fungiformes linguales es una condición benigna y relativamente frecuente en pacientes con piel oscura. Suele aparecer en la segunda o tercera décadas de la vida y se han descrito casos de herencia autosómica dominante. El diagnóstico es clínico, pero la dermatoscopia es de gran ayuda: presenta un patrón clásico en pétalos de rosa. La patogénesis se desconoce y no hay tratamientos efectivos. Caso clínico: Reportamos el caso de una niña de 15 años con pigmentación de las papilas fungiformes y con patrón dermatoscópico compatible. Conclusiones: Conocer la existencia de esta afección y su característica dermatoscopia evita realizar pruebas invasivas adicionales, ya que se trata una variante de la normalidad.

Abstract Introduction: Pigmented fungiform papillae of the tongue is a benign condition frequent in dark skin patients. It usually appears in the second or third decade of life, and it has been reported as autosomal dominant inheritance pattern. The diagnosis is clinical, but dermoscopy could be helpful: a classical rose petal pattern is observed. The pathogenesis is unknown, and no treatments are effective. Case report: We report a case of a 15-year-old girl with a pigmented fungiform papillae and a compatible dermatoscopy pattern. Conclusions: Knowing the existence of this entity and its characteristic dermoscopy, avoids additional invasive medical test. We have to know this entity because it is a variant of normality.

RESUMEN Según la ciencia histórica de las enseñanzas políticas y jurídicas, el término democracia, que tiene una historia antigua y rica, ha experimentado un desarrollo progresivo. Pero según la enseñanza de la dialéctica, el desarrollo es siempre la sustitución de un estado cualitativo por otro. Al mismo tiempo, implica la herencia de ciertas características y mecanismos que ocurrieron en las etapas anteriores en una etapa posterior del desarrollo, lo que a su vez determina la secuencia y progresión del desarrollo, de lo contrario, el progreso no sería posible en absoluto. En este contexto, la teoría de la democracia puede observarse en la historia de la relación de sucesión basada en el desarrollo dialéctico del pasado. Las teorías de la democracia directa, liberal, social, pluralista y otras han surgido en diferentes períodos históricos en el proceso de investigación de las cuestiones del concepto, la esencia y las formas de implementación de la democracia en la historia de la educación estatal y jurídica. La manifestación de estas teorías como resultado de la formación constitucional de los distintos estados reveló las ventajas y desventajas de dichas teorías. Este proceso histórico determinó la base de la democracia moderna basada en la teoría de las convenciones en el mundo. Como resultado de la investigación realizada, se determinó que la convención de los modelos democráticos es característica de las constituciones de estas democracias modernas. En los tiempos modernos, las socialdemocracias directas, liberales y pluralistas convergen en las constituciones de Azerbaiyán y otros estados europeos. Pero para una democracia consolidada, las democracias modernas deben desarrollar la democracia electrónica.

ABSTRACT According to the historical science of political and legal teachings, the term democracy, which has an ancient and rich history, has undergone a progressive development. However, according to the teaching of dialectics, development is always the substitution of one quality state for another. At the same time, it implies the inheritance of certain characteristics and mechanisms that occurred in the previous stages in a later stage of development, which in turn determines the sequence and progression of development, otherwise, progress would not be possible at all. In this context, the theory of democracy can be observed in the history of the succession relationship based on the dialectical development of the past. Direct, liberal, social, pluralist, and other theories of democracy have emerged in different historical periods in the process of researching the questions of the concept, essence, and forms of implementation of democracy in the history of state and legal education. The manifestation of these theories as a result of the constitution-building training of individual states revealed the advantages and disadvantages of those theories. This historical process determined the basis of modern democracy based on convention theory in the world. As a result of the conducted research, it was determined that the convention of democracy models is characteristic of the constitutions of these modern democracies. In modern times, direct, liberal, pluralist, social democracies are convergence in the constitutions of Azerbaijan and other European states. But for consolidated democracy, modern democracies must develop electronic democracy.

RESUMEN Introducción: las inmunodeficiencias primarias constituyen un grupo de enfermedades de base genética debido a alteraciones cuantitativas o funcionales de distintos mecanismos implicados en la respuesta inmunológica. De acuerdo a su patrón de herencia pueden ser autosómicas dominantes y recesivas o ligadas al X. Objetivo: describir las bases genéticas y las perspectivas terapéuticas de la Agammaglobulinemia ligada al X. Métodos: se realizó una revisión de la literatura mediante una búsqueda de información en las bases de datos Medline/PubMed, Bireme (Scielo, Lilacs) y la biblioteca médica Cochrane en los meses de octubre y noviembre de 2023. Se empleó una fórmula de búsqueda avanzada. Desarrollo: en la actualidad se han descrito más de 350 inmunodeficiencias primarias, de las cuales en más de 250 se ha mapeado el gen responsable y se sospecha que unos 3000 genes podrían estar relacionados con su origen. La Agammaglobulinemia ligada al X resulta de la pérdida de variantes de función en el gen de la tirosina quinasa de Bruton con locus génico en el brazo largo del cromosoma X en el que se han descrito más de 700 mutaciones exónicas e intrónicas. Conclusiones: la complejidad del diagnóstico molecular de estos trastornos radica en el hecho de la gran heterogeneidad genética que presentan. La terapia de reemplazo de inmunoglobulinas sigue siendo la principal herramienta terapéutica. La edición genética constituye un promisorio enfoque para tratar la Agammaglobulinemia ligada al X y los errores innatos de la inmunidad en sentido general.

ABSTRACT Introduction: primary immunodeficiencies constitute a group of diseases with a genetic basis due to quantitative or functional alterations of different mechanisms involved in the immune response. According to their inheritance pattern they can be autosomal dominant and recessive or X-linked. Objective: to describe the genetic basis and therapeutic perspectives of X-linked agammaglobulinemia. Methods: A literature review was performed by searching the Medline/PubMed, Bireme (Scielo, Lilacs) and Cochrane Medical Library databases in October and November 2023 using an advanced search formula. Development: currently more than 350 primary immunodeficiencies have been described, of which more than 250 have been mapped with the responsible gene and it is suspected that about 3000 genes could be related to their origin. X-linked agammaglobulinemia results from loss of function variants in the Bruton's tyrosine kinase gene with gene locus on the long arm of the X chromosome in which more than 700 exonic and intronic mutations have been described. Conclusions: the complexity of the molecular diagnosis of these disorders lies in the fact of the great genetic heterogeneity they present. Immunoglobulin replacement therapy remains the main therapeutic tool. Gene editing is a promising approach to treat X-linked agammaglobulinemia and inborn errors of immunity in general.