Testamentum tempore pestis: el derecho civil y la bioética frente al testamento en casos de epidemia / Testamentum tempore pestis Civil law and bioethics faced with the testament in cases of epidemics / Testamentum tempore pestis: o Direito civil e a bioética frente ao testamento em casos de epidemia

Resumen: El confinamiento por la pandemia del covid-19 afectó el otorgamiento de testamentos, siendo estos tan necesarios ante las crisis sanitarias cuando las personas precisan decidir el destino de sus bienes y otros actos individuales ante el riesgo de vida. La solemnidad del testamento impide el ejercicio de testar de los pacientes, incluso de las personas sanas. Facilitar el derecho de testar en tiempos de peste tiene contenido bioético, al estar de por medio la vida, salud, autodeterminación y el derecho de decidir el destino patrimonial. El testamento en épocas de pandemia, apoyado en las TIC, es una solución que debe viabilizarse con la ayuda de la digitalización y tecnología, con el fin de permitir el ejercicio de los derechos de última voluntad en aislamiento por contagio.

Abstract: The confinement due to the Covid pandemic affected the granting of wills, which are so necessary in the health crisis when people need to decide the fate of their property and other individual acts at the risk of life. The solemnity of the will impedes the exercise of testamentary rights of patients, even healthy people. Facilitating the right to testament in times of plague has a bioethical content since life, health, self-determination and the right to decide the destiny of property are at stake. The will in times of pandemic, supported by ICTs, is a solution that should be made feasible with the help of digitization and technology in order to allow the exercise of the rights of last will in isolation by contagion.

Resumo: O confinamento pela pandemia da covid-19 afetou a outorga de testamentos, sendo estes muito necessários durante as crises sanitárias, quando as pessoas precisam decidir o destino de seus bens e outros atos individuais diante do risco de vida. A solenidade do testamento impede o exercício de testar dos pacientes, inclusive das pessoas sadias. Facilitar o direito de testar em tempos de peste tem conteúdo bioético, al estar de por médio (no entendí el significado de esto) a vida, saúde, autodeterminação e o direito de decidir o destino patrimonial. O testamento em épocas de pandemia, apoiado nas TIC, é uma solução que deve viabilizar-se com a ajuda de digitalização e tecnologia, a fim de permitir o exercício dos direitos de última vontade no isolamento por contagio.

BRCA1/BRCA2 Pathogenic Variant Breast Cancer: Treatment and Prevention Strategies

Hereditary breast cancer is known for its strong tendency of inheritance. Most hereditary breast cancers are related to BRCA1/BRCA2 pathogenic variants. The lifelong risk of breast cancer in pathogenic BRCA1 and BRCA2 variant carriers is approximately 65% and 45%, respectively, whereas that of ovarian cancer is estimated to be 39% and 11%, respectively. Therefore, understanding these variants and clinical knowledge on their occurrence in breast cancers and carriers are important. BRCA1 pathogenic variant breast cancer shows more aggressive clinicopathological features than the BRCA2 pathogenic variant breast cancer. Compared with sporadic breast cancer, their prognosis is still debated. Treatments of BRCA1/BRCA2 pathogenic variant breast cancer are similar to those for BRCA-negative breast cancer, mainly including surgery, radiotherapy, and chemotherapy. Recently, various clinical trials have investigated poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor treatment for advanced-stage BRCA1/BRCA2 pathogenic variant breast cancer. Among the various PARP inhibitors, olaparib and talazoparib, which reached phase III clinical trials, showed improvement of median progression-free survival around three months. Preventive and surveillance strategies for BRCA pathogenic variant breast cancer to reduce cancer recurrence and improve treatment outcomes have recently received increasing attention. In this review, we provide an information on the clinical features of BRCA1/BRCA2 pathogenic variant breast cancer and clinical recommendations for BRCA pathogenic variant carriers, with a focus on treatment and prevention strategies. With this knowledge, clinicians could manage the BRCA1/BRCA2 pathogenic variant breast cancer patients more effectively.

A Novel Heterozygous Missense Variant (c.667G>T;p.Gly223Cys) in USH1C That Interferes With Cadherin-Related 23 and Harmonin Interaction Causes Autosomal Dominant Nonsyndromic Hearing Loss

BACKGROUND: Pathogenic variants of USH1C, encoding a PDZ-domain-containing protein called harmonin, have been known to cause autosomal recessive syndromic or nonsyndromic hearing loss (NSHL). We identified a causative gene in a large Korean family with NSHL showing a typical pattern of autosomal dominant (AD) inheritance.METHODS: Exome sequencing was performed for five affected and three unaffected individuals in this family. Following identification of a candidate gene variant, segregation analysis and functional studies, including circular dichroism and biolayer interferometry experiments, were performed.RESULTS: A novel USH1C heterozygous missense variant (c.667G>T;p.Gly223Cys) was shown to segregate with the NSHL phenotype in this family. This variant affects an amino acid residue located in the highly conserved carboxylate-binding loop of the harmonin PDZ2 domain and is predicted to disturb the interaction with cadherin-related 23 (cdh23). The affinity of the variant PDZ2 domain for a biotinylated synthetic peptide containing the PDZ-binding motif of cdh23 was approximately 16-fold lower than that of the wild-type PDZ2 domain and that this inaccessibility of the binding site was caused by a conformational change in the variant PDZ2 domain.CONCLUSIONS: A heterozygous variant of USH1C that interferes with the interaction between cdh23 and harmonin causes novel AD-NSHL.

Prenatal diagnosis of harlequin ichthyosis: a case report

Nomeação e pecado original em lacan: um recorte a partir dos testemunhos de descendentes de nazistas notórios / Nomination and original sin in lacan: a reading from the testimonies of descendants of notorious nazis

RESUMO: O artigo investiga a relação entre nomeação e herança a partir da constatação lacaniana de que o sobrenome é símbolo do quinhão ao qual o sujeito tem acesso: o pecado dos pais tal como Kierkegaard o designa. Ao examinar a nomeação e o pecado herdado em Kierkegaard à luz da psicanálise, observamos aproximações entre esses elementos que podem atravessar o engajamento do sujeito com a sua história e o modo como se autoriza a ser chamado filho de.

Abstract: This study discusses the relation between nomination and inheritance starting from the Lacanian observation that the surname is a symbol of the legacy to which the subject has access: the parent's sin as Kierkegaard designates it. When examining, in the light of psychoanalysis, the nomination and ancestral sin in Kierkegaard, we observe approximations between these elements that can permeate the subject engagement with his history and the way he authorizes himself to be called son of.

The Connection between Charles Darwin's Evolutionary Theory of ‘Heredity of Behaviors’ and the 19th Century Neuroscience: The Influence of Neuroscience on Darwin's Overcoming of Lamarck's Theory of Evolution / 의사학

The nineteenth century neuroscience studied the instinct of animal to understand the human mind. In particular, it has been found that the inheritance of unconscious behavior like instinct is mediated through ganglion chains, such as the spinal cord or sympathetic nervous system, which control unconscious reflexes. At the same time, the theory of Inheritance of Acquired Characteristics (hereafter ‘IAC’) widely known as Lamarck's evolutionary theory provided the theoretical frame on the origin of instinct and the heredity of action that the parental generation's habits were converted into the nature of the offspring generation. Contrary to conventional knowledge, this theory was not originally invented by Lamarck, and Darwin also did not discard this theory even after discovering the theory of natural selection in 1838 and maintained it throughout his intellectual life. Above all, in the field of epigenetics, the theory of ‘IAC’ has gained attention as a reliable scientific theory today. Darwin discovered crucial errors in the late 1830s that the Lamarck version's theory of ‘IAC’ did not adequately account for the principle of the inheritance of unconscious behavior like instinct. Lamarck's theory regarded habits as conscious and willful acts and saw that those habits are transmitted through the brain to control conscious actions. Lamarck's theory could not account for the complex and elaborate instincts of invertebrate animals, such as brainless ants. Contrary to Lamarck's view, Darwin established the new theory of ‘IAC’ that could be combined with contemporary neurological theory, which explains the heredity of unconscious behavior. Based on the knowledge of neurology, Darwin was able to translate the ‘principle of habit’ into a neurological term called ‘principle of reflex’. This article focuses on how Darwin join the theory of ‘IAC’ with nineteenth century neuroscience and how the neurological knowledge from the nineteenth century contributed to Darwin's overcoming of Lamarck's ‘IAC’. The significance of this study is to elucidate Darwin's notion of ‘IAC’ theory rather than natural selection theory as a principle of heredity of behavior. The theory of ‘IAC’ was able to account for the rapid variation of instincts in a relatively short period of time, unlike natural selection, which operates slowly in geological time spans of tens of millions of years. The nineteenth century neurological theory also provided neurological principles for ‘plasticity of instinct,’ empirically supporting the fact that all nervous systems responsible for reflexes respond sensitively to very fine stimuli. However, researchers of neo-Darwinian tendencies, such as Richard Dawkins and evolutionary psychologists advocating the ‘selfish gene’ hypothesis, which today claim to be Darwin's descendants, are characterized by human nature embedded in biological information, such as the brain and genes, so that it cannot change at all. This study aims to contribute to reconstructing the evolutionary discourse by illuminating Darwin's insights into the “plasticity of nature” that instincts can change relatively easily even at the level of invertebrates such as earthworms.

First identified Korean family with Tatton-Brown-Rahman Syndrome caused by the novel DNMT3A variant c.118G>C p.(Glu40Gln)

Tatton-Brown-Rahman Syndrome (TBRS), an overgrowth syndrome caused by heterozygous mutation of DNMT3A, first was described in 2014. Approximately 60 DNMT3A variants, including 32 missense variants, have been reported, with most missense mutations located on the DNMT3A functional domains. Autosomal dominant inheritance by germ-line mutation of DNMT3A has been reported, but vertical transmission within a family is extremely rare. Herein, we report the first Korean family with maternally inherited TBRS due to the novel heterozygous DNMT3A variant c.118G>C p.(Glu40Gln), located outside the main functional domain and identified by multigene panel sequencing. The patient and her mother had typical clinical features, including tall stature during childhood, macrocephaly, intellectual disability, and characteristic facial appearance. TBRS shows milder dysmorphic features than other overgrowth syndromes, potentially leading to underdiagnosis and underestimated prevalence; thus, targeted multigene panel sequencing including DNMT3A will be a useful tool in cases of overgrowth and unexplained mild intellectual disability for early diagnosis and genetic counseling.

NR3C1 Polymorphisms for Genetic Susceptibility to Schizophrenia

OBJECTIVES: Psychological stress has been known to increase the risk of schizophrenia. Because stress responses are mainly mediated by cortisol, the action of the glucocorticoid receptors (Nuclear Receptor Subfamily 3 Group C Member 1, NR3C1) is possibly related to the pathogenesis of schizophrenia. In this study, we investigated the associations between polymorphisms of NR3C1 and schizophrenia.METHODS: Four single nucleotide polymorphisms (SNPs) (rs17100236, rs2963155, rs9324924, and rs7701443) of NR3C1 were genotyped in 208 patients with schizophrenia and 339 healthy individuals. A chi-square test was performed to test differences in allele distributions among groups. A multiple logistic regression model was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), and multiple inheritance models to analyze the associations between schizophrenia and SNPs (the dominant, recessive and additive models).RESULTS: The minor allele frequencies of two SNPs were significantly higher in the schizophrenia group than in those of the control group (rs2963155 G > A : 0.25 vs. 0.18, p = 0.0066 ; rs7701443 A > G : 0.40 vs. 0.33, p = 0.012). The genotype frequencies of two SNPs were found to be significantly different between patients with schizophrenia and controls in the dominant model (rs2963155 : AG/GG vs. AA, OR = 1.66, 95% CI = 1.16–2.38, p = 0.0055, rs7701443 : AG/AA vs. GG, OR = 1.61, 95% CI = 1.11–2.34, p = 0.01) and the log-additive model (rs2963155 : AG vs. GG vs. AA, OR = 1.54, 95% CI = 1.13–2.10, p = 0.0067).CONCLUSIONS: This study showed significant associations between NR3C1 polymorphisms and schizophrenia. It suggests that NR3C1 may play a role in the pathogenesis of schizophrenia.

Steatocystoma multiplex: A case report of a rare entity

Steatocystoma multiplex is an uncommon benign skin disease, which typically manifests as numerous intradermal cysts that can be scattered anywhere on the body. Although usually asymptomatic, it can be significantly disfiguring. One type of steatocystoma multiplex is known to be associated with the autosomal dominant inheritance of a mutation in the gene coding for keratin 17 (KRT17). In such cases, it is often concurrent with other developmental abnormalities of the ectoderm-derived tissues, such as the nails, hair, and teeth. To the best of our knowledge, few cases have been reported of steatocystoma multiplex of the oral and maxillofacial region. This report describes a case of steatocystoma multiplex of both sides of the neck and multiple dental anomalies, with a focus on its clinical, radiological, and histopathological characteristics, as well as the possibility that the patient exhibited the familial type of this condition.

Pregnancy and Childbirth Experiences of Women with Epilepsy: A Phenomenological Approach

PURPOSE: This study sought to understand and describe the pregnancy and childbirth experiences of women with epilepsy (WWE). METHODS: Datawere collected from 2016e2017 through in-depth individual interviews with 12 WWE who experienced childbirth within 36 months. Verbatim transcripts were analyzed following Colaizzi's phenomenological analysis to uncover the meaning of the experiences of the participants. RESULTS: The pregnancy and childbirth experiences of WWE were clustered into four theme clusters and 8 themes from20 meaning units: 1) Feeling anxious due to unplanned pregnancy and unexpected changes; 2) Standing at crossroads that never guarantee satisfaction; 3) Carrying a burden of fearful expectation and daily routines; 4) Enjoying rewards of pregnancy and childbirth as a woman with epilepsy. CONCLUSION: WWE had strong anxiety about the possible abnormality of their babies during pregnancy. They had mixed feelings about delivery and had to make a tough decision about breastfeeding because of antiepileptic drugs use. After childbirth, they had increased fear about the possible inheritance of the illness and had a hard time managing the burden of childcare and seizure control. However, pregnancy allows these women to gain disease awareness and further appreciate the importance of their health. The study results indicate the need for multidisciplinary intervention for WWE, before, during, and after pregnancy to increase communication with health professionals. Especially, preconception counselling and education led by nurses are required.

A Case of Focal Acral Hyperkeratosis with Autosomal Dominant Inheritance / 대한피부과학회지

Focal acral hyperkeratosis (FAH) is a rare genodermatosis inherited by autosomal dominant transmission; however, some sporadic cases have also been reported. FAH is characterized by multiple late-onset crateriform hyperkeratotic papules with a yellow color on the border of the hands and feet. A 31-year-old man presented with yellowish discrete flat-topped papules on the lateral side of his palms and fingers. The patient had a family history of similar lesions throughout three generations. The histological findings revealed hyperkeratosis with mild hypergranulosis in the epidermis, and the dermis showed no specific changes including elastorrhexis. These clinicopathologic findings were consistent with the diagnosis of FAH. Herein, we report a rare case of FAH with autosomal dominant inheritance.

Two Korean Families with Limb-Girdle Muscular Dystrophy Type 1D Associated with DNAJB6 Mutations

Limb-girdle muscular dystrophies (LGMD) are heterogeneous disorders with autosomal inheritance. Autosomal dominant LGMD mapped to 7q36.3 has been classified as LGMD type 1D (LGMD1D) in the Human Gene Nomenclature Committee Database. LGMD1D is characterized predominantly by limb-girdle weakness and may also show a bulbar symptom in some cases. In the past, the frequency of this disease was uncommon, and this disorder was mainly found in Europe and the United States. However, recently, this disorder has been reported in Asia, including Japan, Korea, and Taiwan. Here, we report on three LGMD1D patients, including one with a novel mutation in DNAJB6, c.298T>A. While two patients complained of limb-girdle weakness, as would be expected, one patient had distal weakness. They had various serum creatine kinase levels. Radiologic findings in one patient showed fatty degeneration and atrophy in the posterior part of distal muscles. Pathologic findings in one of the patients showed rimmed vacuoles. Although LGMD1D is still uncommon in Korea, we discovered three Korean patients with LGMD1D, including one novel mutation in DNAJB6, p.Phe100Ile (c.298T>A).

1q21.1 microdeletion identified by chromosomal microarray in a newborn with upper airway obstruction

A 1q21.1 microdeletion is an extremely rare chromosomal abnormality that results in phenotypic diversity and incomplete penetrance. Patients with a 1q21.1 microdeletion exhibit neurological-psychiatric problems, microcephaly, epilepsy, facial dysmorphism, cataract, and thrombocytopenia absent radius syndrome. We reported a neonate with confirmed intrauterine growth restriction (IUGR), micrognathia, glossoptosis, upper airway obstruction, facial dysmorphism, and eye abnormality at birth as well as developmental delay at the age of 1 year. These clinical manifestations, except for the IUGR and upper airway obstruction, in the neonate indicated a 1q21.1 microdeletion. Here, we report a rare case of a 1q21.1 microdeletion obtained via paternal inheritance in a newborn with upper airway obstruction caused by glossoptosis and tracheal stenosis.

Primary Autosomal Recessive Distal Renal Tubular Acidosis Caused by a Common Homozygous SLC4A1 Mutation in Two Lao Families

Primary distal renal tubular acidosis (dRTA) caused by mutations of the SLC4A1 gene, which encodes for erythroid and kidney isoforms of anion exchanger, shows marked difference in inheritance patterns and clinical features in different parts of the world. While the disease shows autosomal dominant inheritance without any red cell morphological abnormalities in the temperate countries, it is almost invariably recessive, and often accompanies red cell morphological abnormalities or hemolytic anemia in the tropics, especially in Southeast Asia. Here, we report three patients with autosomal recessive (AR) dRTA, presenting with typical findings of failure to thrive and rickets, from two unrelated Lao families. The mutational analyses revealed that all three patients harbored the same homozygous SLC4A1 mutation, p.Gly701Asp. Adequate supplementation of alkali and potassium resulted in remarkable improvement of growth retardation and skeletal deformities of the patients. This is the first case report of Lao patients with AR dRTA caused by SLC4A1 mutations.

Pedigree Analysis and Audiological Investigations of Otosclerosis: An Extended Family Based Study

BACKGROUND AND OBJECTIVES: To analyse the audiometric profile and the pedigree of a large family with otosclerosis to understand the inheritance pattern and its implication in clinical management of the disease. SUBJECTS AND METHODS: Pedigree analysis was performed on the basis of family history and audiometric tests. Pure tone audiometry, tympanometry, and acoustic reflexes were evaluated for the family members. Audiometric analysis was also carried out for the individuals who have already underwent corrective surgery at the time of study. RESULTS: Out of 112 family members, 17 were affected individuals, and 11 of them were surgically confirmed. Hearing loss (HL) started unilaterally and progressed to bilateral form. Otosclerosis was presented in early 20’s in the first and second generations but it was delayed to mid-late 30’s in the fourth generation. An affected female was diagnosed with otosclerosis during her pregnancy. Though the disease was familial, a mother of four affected offspring in this family did not develop otosclerosis until she died at the age of 84. CONCLUSIONS: The five-generation family, which was analysed in the present study, exhibited autosomal dominant inheritance of otosclerosis with reduced penetrance. Bilateral HL and pregnancy-aggravated otosclerosis were observed in this family. It was found for the first time that the age of onset of the disease delayed in the successive generations. The current study indicated the importance of detailed pedigree analysis for better clinical management of otosclerosis.

Clinical genetics of defects in thyroid hormone synthesis

Thyroid dyshormonogenesis is characterized by impairment in one of the several stages of thyroid hormone synthesis and accounts for 10%–15% of congenital hypothyroidism (CH). Seven genes are known to be associated with thyroid dyshormonogenesis: SLC5A5 (NIS), SCL26A4 (PDS), TG, TPO, DUOX2, DUOXA2, and IYD (DHEAL1). Depending on the underlying mechanism, CH can be permanent or transient. Inheritance is usually autosomal recessive, but there are also cases of autosomal dominant inheritance. In this review, we describe the molecular basis, clinical presentation, and genetic diagnosis of CH due to thyroid dyshormonogenesis, with an emphasis on the benefits of targeted exome sequencing as an updated diagnostic approach.

A frameshift mutation in the TRPS1 gene showing a mild phenotype of trichorhinophalangeal syndrome type 1

Tricho-rhino-phalangeal syndrome (TRPS) is a hereditary disorder characterized by craniofacial and skeletal abnormalities. A mutation of the TRPS1 gene leads to TRPS type I or type III. A 20-year-old male patient visited our neurologic department with chronic fatigue. He presented with short stature, sparse hair, pear-shaped nose, and brachydactyly. Radiologic study showed short metacarpals, metatarsals with cone-shaped epiphyses, hypoplastic femur and hip joint. Panel sequencing for OMIM (Online Mendelian Inheritance in Man) listed genes revealed a de novo heterozygous frameshift mutation of c.1801_1802delGA (p.Arg601Lysfs*3) of exon 4 of the TRPS1 gene. The diagnosis of TRPS can be challenging due to the rarity and variable phenotype of the disease, clinicians should be aware of its characteristic clinical features that will lead a higher rate of diagnosis.

Pseudohypoparathyroidism type 1b due to paternal uniparental disomy of chromosome 20q: A case report

Pseudohypoparathyroidism type 1b (PHP 1b) is the result of end organ resistance to parathyroid hormone (PTH) in the absence of any features of Albright's hereditary osteodystrophy. There are two subtypes of PHP 1b with different genetic mechanisms. One subtype is related to a maternally derived 3kb microdeletion involving STX 16 gene, and is inherited in an autosomal dominant mode. Familial autosomal dominant inheritance of PHP 1b is relatively rare. The other subtype is associated with more extensive loss of imprinting at the GNAS locus that affects at least one additional differential methylated (hypermethylation at neuroendocrine secretory protein and hypomethylation at antisense transcript and or extra-large stimulatory G protein region) without microdeletion of the STX 16 or AS gene. It can be sporadic due to an imprinting defect in the GNAS gene. In our case, an 8-year-old girl was referred for suspected PHP with no feature of Albright hereditary osteodystrophy. Blood test results revealed hypocalcemia and hyperphosphatemia. Elevated PTH was also checked. There was no family history of endocrine or developmental problem. Her intelligence was normal, but she had inferior sociability at that time. Based on above, we diagnosed a rare case of paternal uniparental disomy of the long arm of chromosome 20 as the cause of PHP 1b by microsatellite marker test of chromosome 20.

Current Clinical Features of Febrile Seizures in a Pediatric Emergency Room / 이화의대지

OBJECTIVES: To expand current knowledge on febrile seizures (FSs), the most common childhood seizure disorder, we investigated clinical features and risk factors of FS in the pediatric emergency department of a center in western Seoul. METHODS: Children with FS that visited the pediatric emergency room of the Ewha Womans University Medical Center from January to December 2014 were included in this study. A retrospective medical record review was conducted for a total of 404 seizure events relative to 265 patients. RESULTS: A total of 150 boys and 115 girls were enrolled. Children presenting their first FSs were 70.9% (n=188). Average age of FS onset was 28.9 months. Family history was reported in 95 children (36.8%) with higher relevance of paternal inheritance (44.2%, n=42/95). More than half of the seizures (56.4%, n=228/404) occurred on the first day of fever. The most common cause of fever was upper respiratory tract infection (65.8%, n=266/404). Children attending a daycare center had higher incidence of multiple FS compared to those cared for at home. Approximately one third of seizure events (31.7%, n=128/404) were admission cases, mainly because of prolonged fever. CONCLUSION: FS is a common neurologic disorder with relatively high admission rate among pediatric emergency department visits. Daycare attendance is associated with current increased incidence of multiple FS. Further study with long-term follow up is necessary to expand knowledge on improving clinical care strategy in FS.

Genetics of hereditary nephrotic syndrome: a clinical review / 소아과

Advances in podocytology and genetic techniques have expanded our understanding of the pathogenesis of hereditary steroid-resistant nephrotic syndrome (SRNS). In the past 20 years, over 45 genetic mutations have been identified in patients with hereditary SRNS. Genetic mutations on structural and functional molecules in podocytes can lead to serious injury in the podocytes themselves and in adjacent structures, causing sclerotic lesions such as focal segmental glomerulosclerosis or diffuse mesangial sclerosis. This paper provides an update on the current knowledge of podocyte genes involved in the development of hereditary nephrotic syndrome and, thereby, reviews genotype-phenotype correlations to propose an approach for appropriate mutational screening based on clinical aspects.