Síndromes poliglandulares autoimunes: uma revisão geral em busca novas evidências / Autoimmune polyglandular syndromes: a general review in search of new evidence / Síndromes poliglandulares autoinmunes: una visión general de la búsqueda de nuevas evidencias

As Síndromes Poliglandulares Autoimunes (SPA) são consideradas endocrinopatias raras em que ocorrem alterações autoimunes nas glândulas endócrinas, acompanhadas de outras doenças não endócrinas. Tendo em vista a complexidade de associações em cada subtipo, suas particularidades e gênese dos mecanismos envolvidos, este artigo busca, através de uma meta-analise, equacionar seus aspectos descritivos mais atuais e importantes para a prática clínica. As SPA podem ser classificadas nos tipos I, II, III e IV de acordo com a idade de início e os órgãos afetados. Interações complexas entre fatores genéticos, epigenéticos e ambientais provavelmente contribuem para o desenvolvimento dessas síndromes, que idealmente devem ser diagnosticadas em estágios iniciais, dada a sua alta morbidade e mortalidade. O tratamento adequado de cada uma das alterações é essencial para preservar a qualidade de vida dos pacientes.

Autoimmune Polyglandular Syndromes (APS) are considered rare endocrinopathies characterized by autoimmune alterations in the endocrine glands, accompanied by other non-endocrine diseases. Bearing in mind the complexity of associations in each subtype, its particularities and the genesis of the mechanisms involved, this article seeks, through meta-analysis, to equate its most current and important descriptive aspects for clinical practice. APS can be classified into types I, II, III and IV according to age of onset and affected organs. Complex interactions between genetic, epigenetic, and environmental factors likely contribute to the development of these syndromes, which ideally should be diagnosed at an early stage, given their high morbidity and mortality. Appropriate treatment of each of the alterations is essential to preserve the quality of life of patients.

Los Síndromes Polilandulares Autoinmunes (SPA) se consideran endocrinopatías raras en las que se producen cambios autoinmunes en las glándulas endocrinas, acompañadas de otras enfermedades no endocrinas. En vista de la complejidad de las asociaciones en cada subtipo, sus particularidades y la génesis de los mecanismos involucrados, este artículo busca, a través de un metaanálisis, considerar sus aspectos descriptivos más actualizados e importantes para la práctica clínica. Las ZEPA podrán clasificarse en los tipos I, II, III y IV según la edad de inicio y los órganos afectados. Las complejas interacciones entre los factores genéticos, epigenéticos y ambientales probablemente contribuyan al desarrollo de estos síndromes, que idealmente deberían ser diagnosticados en etapas tempranas, dada su alta morbilidad y mortalidad. El tratamiento adecuado de cada cambio es esencial para preservar la calidad de vida de los pacientes.

Intracranial Calcification in a Case of Seizure Disorder

A patient with repeated episodes of Seizures and elevated Blood Pressure for 2 days, was admitted in a primary care set up initially, followed by admission to our Institute where he was thoroughly worked up to find the possible etiology behind the presentation. Extensive investigations and imaging led to the conclusion that the patient had Idiopathic Intracranial Calcification after the possible secondary causes of Intracranial Calcification were ruled out

Pasado presente y futuro de la estimulación ovárica en el tratamiento de la infertilidad / Past, present and future of ovarian stimulation in infertility treatment

La mejor comprensión de la fisiología reproductiva y la disponibilidad de más y mejores recursos diagnóstico/terapéuticos permiten individualizar la estimulación ovárica y hacerla más efectiva (mejores resultados), eficiente (en menos tiempo y con dosis más bajas), segura (con menos y más leves complicaciones), cómoda (menos molestias y autonomía) y accesible (para más personas, a menores costos). Con tecnología de ADN recombinante se dispone ahora de todas las gonadotrofinas e incluso algunas con formas moleculares modificadas para aumentar la duración de acción y disminuir el número de inyecciones. El esquema más utilizado es el de FSH recombinante junto con antagonistas de GnRH. Hay indicaciones específicas para agregar LH o coadyuvantes como hGH o andrógenos transdérmicos. La estimulación ovárica, además de infertilidad, se usa para la preservación de la fertilidad. Cada vez se implementan más estrategias como acumulación de óvulos, esquemas no convencionales (random start, DuoStim y otros) junto a vitrificación ovular, estudio genético preimplantatorio, transferencias embrionarias diferidas y la investigación continúa. Se pronostican mejoras en un futuro próximo, entre otras antagonistas por vía oral y estudio genético de pacientes para diagnosticar mutaciones o polimorfismos de gonadotrofinas y sus receptores. Aunque ya es factible individualizar la estimulación y volverla más efectiva, segura y amigable, así como ofrecer otras opciones a pacientes de mal pronóstico.

Due to an increased understanding of reproductive physiology and to the availability of more and better diagnostic/therapeutic agents, ovarian stimulation through individualization, has become more effective (improved results), efficient (shorter span and lower doses), safe (less and milder complications), comfortable (less discomfort and dependance) and affordable (for more people at lower cost). All gonadotrophins are now available by recombinant DNA technology, including some modified compounds for specific purposes such as longer action and fewer injections. The most popular ovarian regime uses recombinant FSH and GnRH antagonist. There are precise indications for adding LH or adjuncts like hGH or transdermal androgens. Besides infertility, ovarian stimulation is also indicated for fertility preservation. Strategies like oocyte accumulation, non-conventional stimulation protocols (random start, DuoStim and others), oocyte vitrification, preimplantation genetic testing, freeze-all, deferred embryo transfer for particular cases are becoming popular, and the research still goes on. Future advances like oral GnRH antagonists, and the study of mutations and polymorphisms for gonadotropins and its receptors are foreseen. Today through individualization, ovarian stimulation is safe, effective and friendly, also we can offer good options to bad prognosis patients

Sirenomelia associated with VACTERL and VACTERL-H syndrome / Sirenomelia asociaciada con síndrome de VACTERL y VACTERL-H

Sirenomelia or mermaid syndrome is an extremely rare congenital lethal malformation with a frequency between 1.5 and 4.2 per 1 000 000 pregnancies.The association of sirenomelia with the VACTERL association is very rare, with twenty cases reported in the literature and only two cases with VACTERL-H. We present two cases of sirenomelia, type I and type II associated with VACTERL-H and VACTERL syndromes and we review the literature. First time pregnancy women aged 15 and 40 years, without harmful habits and diseases, where between 25-27 gestational week (GW) the prenatal study identifies malformative fetus and the pregnancy is interrupted by medical evidence. The fetopathological examination in the first case identified sirenomelia type I associated with myelomeningocele, hydrocephalus, anal imperforation, single umbilical artery, bilateral renal agenesis, ureteral and bladder agenesis, tracheo-esophageal fistule, agenesis of external genitals, monkey fold of the left palm of the hand - VACTERL-H. In the second case, where genetic testing is normal, sirenomelia type II associated with agenesis of external genitalia, anal imperforation, myelomeningocele, dolichocrania, macroglossia, low set ears, left preauricular skin tag, long philtrum, lung hypoplasia, split cadiac apex, single umbilicalis artery, blind end colon, hepatomegaly, accessory spleen, polycystic horseshoe kidney, uterine and vaginal agenesis, presence of two ovaries and duodenal stenosis - VACTERL association. This two cases, lead us to believe that sirenomelia and the VACTERL association are probably different manifestations of a pathogenetic process leading to disorders of blastogenesis at different levels during embryonic development.

La sirenomelia es una malformación congénita y excepcionalmente rara, con una frecuencia entre 1,5 y 4,2 en un millón de embarazos. La combinación de la sirenomelia con el síndrome de VACTERL es igualmente rara. La literatura especializada informa sobre la existencia de una veintena de casos solamente; en lo que respecta a su asociación con el síndrome de VACTERL-H se conocen solo dos casos. Luego de realizar una revisión de la literatura presentamos dos casos de sirenomelia asociada con los síndromes de VACTERL-H y de VACTERL En el estudio se analizaron los primeros embarazos de dos mujeres, edad de 15 y de 40 años, respectivamente, ambas mujeres completamente sanas y sin hábitos viciosos. Entre la vigésima quinta y la vigésima séptima semana gestacional (SG) del embarazo ambas mujeres, el análisis prenatal comprueba la existencia de malformación del feto debido a lo cual los embarazos fueron interrumpidos por prescripción médica. El análisis fetopatológico del primer caso comprueba la existencia de sirenomelia de tipo I asociada con mielomeningocele, hidrocefalia, atresia anal, arteria umbilical única, agenesia bilateral de los riñones y de los ureteres que transportan la orina desde los riñones hasta la vejiga, fístula traqueoesofágica, agenesia de los órganos genitales externos, línea simiesca en la palma de la mano izquierda - VACTERLH. En el segundo caso, en que el análisis genético ha resultado normal, se observó la presencia de sirenomelia de tipo II asociada con agenesia de los órganos genitales externos, atresia anal, mielomeningocele, dolicocrania, macroglosia, orejas bajas, filtrum alargado, hipoplasia pulmonar, ápice cardíaco escindido, arteria umbilical única, colon terminado en ciego, bazo accesorio, poliquistosis renal, riñón en herradura, agenesia vaginal y de útero, presencia de dos ovarios y estenosis duodenal - VACTERL asociación. Los dos casos investigados permiten llegar a la conclusión de que la sirenomelia y su combinación con el síndrome de VACTERL probablemente sean manifestaciones diferentes de un proceso patogenético que conlleva la alteración de la blastogénesis en distintos niveles durante el proceso del desarrollo embrionario.

Geo-herbalism study of Magnoliae Officinalis Cortex / 中国中药杂志

Magnoliae Officinalis Cortex( MOC),the stem bark of Magnolia officinalis( MO) and M. officinalis var. biloba( MOB),is a main ingredient in more than 200 types of Chinese formulae commonly used in clinics. MO and MOB are widely distributed in China,from Sichuan of the west to Zhejiang province of the east and from Shannxi province in the north to Guangxi province in the south. This review summarizes new findings on geo-heralism of MOC concerning textual research,plants taxonomy,genetic study,chemical study,and pharmacological activity,resulting in the following views. ①The original plants of MOC are suggested to be divided into three geographic clans according to the form of leave and the result of genetic research; ②Concentrations of magnolol,honokiol,magnoloside A,magnoloside B,magnoflorine,and β-eudesmol in samples collected from different geographic areas are varied;③Samples of MOC produced in Hubei and Sichuan were traditionally regarded as Dao-di herbs,which were called Chuanpo,and the pure haplotype of MOC produced in Hubei may become a genetic index.

Frecuencia de aneuploidias segmentarias en biopsias de trofoectodermo durante un ciclo de FIV y su relación con la edad materna / Frequency of segmental aneuploidies in trophectoderm biopsies during an IVF cycle and its relationship with maternal age

Resumen ANTECEDENTES: las aneuploidias segmentarias se han propuesto como posible explicación para el subgrupo de embriones euploides transferidos al útero, que no logran un recién nacido saludable. OBJETIVO: conocer la frecuencia de aneuploidias cromosómicas segmentarias en biopsias de trofoectodermo durante un ciclo de fertilización in vitro y su relación con la edad materna. MATERIALES Y MÉTODOS: estudio retrospectivo efectuado en un centro privado de reproducción asistida de México de ciclos (2015-2016) en los que se obtuvieron embriones en estadio de blastocisto (día 5 y 6). Análisis mediante tamizaje genético preimplantacional, en su variante de microarreglos de polimorfismo de nucleótido único (SNP microarrays). Análisis con el algoritmo "Parental Support" (Natera) que permite la identificación de aneuploidias numéricas y segmentarias (pérdidas-duplicaciones). RESULTADOS: se incluyeron 615 blastocistos de 148 ciclos; los resultados se dividieron en 4 rangos, dependiendo de la edad materna: menos de 35, de 35 a 37, de 38 a 40 y más menos 40 años de edad. El 50.3% de los blastocistos fueron aneuploides, y de éstos 10.2% tuvieron aneuploidias segmentarias (6.8% solo pérdidas-duplicaciones y 3.4% pérdidas-duplicaciones más aneuploidias numéricas). Las pérdidas-duplicaciones disminuyeron con el aumento de la edad materna. Todos los resultados tuvieron tendencias más claras cuando solo se tomaron en cuenta los blastocistos aneuploides. CONCLUSIONES: las pérdidas-duplicaciones se encuentran en gran porcentaje de embriones en estadio de blastocisto y tienen una relación inversamente proporcional a la edad materna.

Abstract BACKGROUND: Segmental aneuploidies have been suggested as a possible explanation for the subgroup of euploid embryos transferred to the uterus, which have failed to produce a healthy child. OBJECTIVE: know the frequency of segmental chromosome aneuploidies in trophectoderm biopsies during IVF cycle and its relationship with maternal age. MATERIALS AND METHODS: 615 blastocysts from 148 cycles (2014-2016) were included, which were analyzed with preimplantation genetic screening (PGS), in its variant of single nucleotide polymorphism (SNP microarray), using the algorithm "Parental Support", which allows the identification of numerical aneuploidies and segmental aneuploidies (Deletions/Duplications). The results were divided into four ranges, depending of maternal age "<35", "35 to 37", "38 to 40" and "≥41". RESULTS: 50.3% of the blastocysts were aneuploid, of which 10.2% had segmental aneuploidies (6.8% only Deletions/Duplications and 3.4% Deletions/Duplications plus numerical aneuploidies). Deletions/Duplications decreased with increasing maternal age. The aforementioned results presented clearer trends when only aneuploid blastocysts were taken into account. CONCLUSIONS: The Deletions/Duplications is present in a large percentage of embryos in the blastocyst stage and show an inversely proportional relation to maternal age.

Desarrollo embrionario preimplantacional, en ciclos de fecundación in vitro con ovodonación y estudio genético / Preimplantational embryo development in in vitro fertilization cycles with oocyte donation and genetic studies

Introducción. Los estudios genéticos preimplantacionales son cada vez más utilizados con la esperanza de conseguir mejores tasas de implantación y nacido vivo, así como una disminución en la tasa de abortos; por ello resulta necesario analizar estos procedimientos. Objetivo. Evaluar el desarrollo preimplantacional in vitro con ovodonación y estudio genético Diseño. Cohortes retrospectivas. Lugar. Laboratorio Pranor, 20082013. Material. Ciclos de fecundación in vitro con ovodonación (FIV-OD). Intervenciones. Se evaluaron 2 077 ciclos de FIV-OD, los cuales fueron clasificados en tres cohortes: 1) ciclos con biopsia embrionaria en día 3, mediante una incisión en la zona pelúcida (ZP) embrionaria, para exéresis de una blastómera (n=527); 2) ciclos con incisión láser en día 4 del desarrollo embrionario, como parte del procedimiento para la biopsia de trofoblasto (n=131); y, 3) ciclos sin intervención (n=1 419). Principales medidas de resultado. Tasa de fecundación, tasa de blastulación. Resultados. No existió diferencia significativa en la tasa de fecundación de las 3 cohortes (75,0%, 74,6% y 75,9%, respectivamente, p=0,31). La tasa de blastulación en la cohorte 1 fue 42,5%, mientras que en la cohorte 3 fue 47% (RR=1,085; IC=1,051 a 1,120; p<0,0001). Adicionalmente, la cohorte 2 tuvo 51,9%, con una diferencia estadísticamente significativa de prevención del riesgo de no blastular con respecto a la cohorte 3 (RR=0,906; IC=0,851 a -0,965; p=0,0017). Conclusiones. El desarrollo preimplantacional hasta blastocisto puede mejorar cuando se utiliza el láser embrionario en día cuatro. Es necesario realizar más estudios para confirmar nuestros resultados.

Introduction: Preimplantational genetic studies are used to achieve a better implantation rate and live birth, as well as to decrease the abortion rate; these techniques should be evaluated. Objective: To evaluate preimplantational embryo development in in vitro fertilization cycles with oocyte donation and genetic studies.. Design: Retrospective cohort study. Setting: Pranor Laboratory, 2008-2013. Material: In vitro fertilization with oocyte donation (IVF-OD) cycles. Interventions: 2 077 cycles of IVF-OD were evaluated, separated in 3 cohorts: Cohort 1, cycles with embryo biopsy on day 3, by means of an incision in the zona pellucida (ZP), for excision of a blastomer (n = 527); Cohort 2, cycles with a laser incision at day 4 of embryo development, for biopsy of the trophoblast in the blastocyst stage (n = 131) and; cohort 3, FIV-OD cycles without any intervention (n = 1 419). Main outcome measures: Fertilization rate, blastulation rate. Results: There was no difference in the fertilization rate among the three groups studied (75.0%, 74.6% and 75.9% respectively, p = 0.31). Blastulation rate in cohort 1, was 42.5%, whereas, in cohort 3, it was 47% (RR = 1.085, CI = 1.0511.120; p <0.0001). In addition, the rate for cohort 2 was 51.9%, with statistical significance, which prevents from non-blastulation risk compared with cohort 3 (RR = 0.906; IC = 0.851-0.965; p = 0.0017). Conclusions: Preimplantational embryo development would improve blastocyst formation when laser is performed on day 4. Further studies are needed to confirm our results.

Genetic Approach of Dizziness / 대한평형의학회지

Patients with recurrent vertigo/dizziness or unsteadiness are a heterogeneous group of complex disorders affecting the peripheral and central vestibular system. They represent a diagnostic challenge for the clinicians, and their genetic basis is largely not known. However, there are some cerebellar and vestibular disorders with a strong genetic background, such as episodic ataxia, spinocerebellar ataxia, vestibular migraine, Meniere's disease, and autosomal dominant nonsyndromic deafness. Furthermore, recent advances in next generation sequencing technique are increasing the number of novel genes associated with cerebellar and vestibular disorders. In this article, we have summarized clinical and molecular genetics findings in neuro-otology.

Diagnostico de hipobetalipoproteinemia en un nino de 8 años? / Diagnosis of hypobetalipoproteinemia in an 8-year-old child? / Diagnostico hipobetalipoproteinemia numa crianca de 8 anos?

La hipobetalipoproteinemia familiar es un trastorno hereditario autosomico dominante que afecta a las lipoproteinas que contienen Apo B, una proteina indispensable para el transporte de los quilomicrones en el intestino y que ademas participa en la sintesis y transporte de las VLDL en el higado. La concentracion de Apo B se usa junto con otras pruebas lipidicas para establecer el riesgo individual de un paciente de desarrollar enfermedad cardiovascular. Presentacion del caso: Paciente de 8 anos, varon, que acude a la consulta de Pediatria del Hospital Universitario Virgen Macarena de Sevilla con sintomas de dolor abdominal, deposiciones blandas y diarreicas, sobrepeso y unas quebradizas. El paciente fue derivado al laboratorio para su estudio con sospecha de hipobetalipoproteinemia. Se le solicito un hemograma, frotis sanguineo, pruebas de coagulacion, bioquimica general y estudio de riesgo vascular. Los datos del estudio bioquimico descartaron la celiaquia (IgA 174 mg/dL [100- 400 mg/dL] y antitransglutaminasa 5 U/mL [< 20]). Las determinaciones incluidas en el perfil de riesgo cardiovascular (RCV) fueron: colesterol total 83 mg/dL (45 mg/dL), c-LDL 32 mg/dL (< 160 mg/dL), colesterol no HDL 35 mg/dL, c-VLDL 3 mg/dL (< 40 mg/dL), trigliceridos 28 mg/dL, Apo-A1 112 mg/dL (119-240 mg/dL), Apo B-100 25 mg/dL (40-125 mg/dL), us-PCR 1,47 mg/dL (< 3 mg/dL), Lp (a) 2 mg/dL (< 30 mg/ dL), homocisteina 5,8 µmol/L (< 15 µmol/L), vitamina A 42 µg/dL (50-200 µg/ dL), vitamina E 1051 µg/dL (50-180 µg/dL) y 25-(OH) D 48,9 ng/mL (30-54 ng/mL) en intervalos de normalidad. El HLA-27 fue negativo. Tras encontrar hallazgos bioquimicos de bajas concentraciones de lipoproteinas con Apo B, se le solicito al paciente una prueba de saliva para realizacion de estudio genetico de LipochipR para mutaciones en el gen de Apo B y PCSK9. Se concluye que el paciente presento una disminucion de la concentracion de las lipoproteinas que contienen Apo B y trigliceridos. La sintomatologia de dolor abdominal y heces pastosas apoyaron el diagnostico clinico. La inexistencia de deficit vitaminico, retraso mental, acantocitosis y demas sintomatologia asociada, hizo pensar en una herencia heterocigota, que con las herramientas disponibles no se pudo describir geneticamente ya que LipochipR no detecta positividad para este paciente para una mutacion de cambio de aminoacidos en el gen y exon de Apo 26, PCSK9-7, PCSK9-4, PCSK9-10.

Familial hypobetalipoproteinemia is a dominant autosomal inherited disorder that affects lipoproteins containing Apo B. It is an essential protein for the transport of chylomicrons in the intestine and it is involved in the synthesis and transport of VLDL in the liver. This concentration is used along with other lipid tests to establish a patient's individual risk of developing cardiovascular disease. This is the case of an 8 year-old male patient who presented at the University Hospital Virgen Macarena in Seville with symptoms of abdominal pain, loose stools and diarrhea, overweight and broken nails. The patient was referred to the laboratory for examination with suspected hypobetalipoproteinemia. He was requested a complete blood count, blood smear, coagulation, biochemistry and vascular risk study. Biochemical data discarded celiac disease (IgA 174 mg/dL [100-400 mg/dL] y antitransglutaminase antibody 5 U/mL [< 20]). Determinations were RCV's profile: Total cholesterol 83 mg/dL (45 mg/dL), c-LDL 32 mg/dL (< 160 mg/dL), non-HDL cholesterol 35 mg/dL, c-VLDL 3 mg/dL (< 40 mg/dL), triglycerides 28 mg/dL, Apo-A1 112 mg/dL (119-240 mg/dL), Apo B-100 25 mg/dL (40-125 mg/dL), us-PCR 1,47 mg/dL (< 3 mg/dL), Lp (a) 2 mg/dL (< 30 mg/dL), Homocysteine 5,8 µmol/L (< 15 µmol/L), Vitamin A 42 µg/dL (50-200 µg/dL), Vitamine E 1051 µg/dL (50-180 µg/dL) and 25-(OH) D 48,9 ng/mL (30-54 ng/mL) in normal ranges. HLA-27 Negative. After biochemical findings of low concentrations of lipoproteins with Apo B100, the patient was requested a saliva test for genetic study conducting LipochipR for mutations of Apo B and PCSK9. It can be concluded that the patient had a decreased concentration of lipoproteins containing Apo-B and triglycerides. The symptoms of abdominal pain and tarry stools supported the clinical diagnosis. The lack of vitamin deficiency, mental retardation, acanthocytosis and other associated sintomatology, made it possible to consider it an heterozygous inheritance. which could not be genetically described with the tools available since LipochipR does not detect in this patient positivity for a mutation to the amino acid change in the gene and exon 26 of Apo, Apo 26, PCSK9-7, PCSK9- 4, PCSK9-10.

Hypobetalipoproteinemia familiar e um disturbio autossomico hereditario dominante que afeta as lipoproteinas contendo Apo--B, uma proteina essencial para o transporte de quilomicrons no intestino e esta envolvido na sintese e transporte de VLDL no figado. A concentracao de Apo-B e utilizada, juntamente com outros testes lipidicos, para estabelecer o risco individual de um paciente de desenvolver doencas cardiovasculares. O caso e o de um paciente de 8 anos, do sexo masculino, que se apresenta para consulta de Pediatria do Hospital Universitario Virgen Macarena, em Sevilha, com sintomas de dor abdominal, fezes brandas e diarreia, sobrepeso e unhas quebradicas. O paciente foi derivado ao laboratorio para exame com suspeita de hypobetalipoproteinemia. Foi pedido um hemograma completo, esfregaco de sangue, coagulacao, bioquimica geral e estudo de risco vascular. Os dados do estudo bioquimico descartaram a doenca celiaca (IgA 174 mg/dL [100-400 mg/dL] e Antitrasglutaminase 5 U/mL [<20]). As determinacoes incluidas no perfil de risco cardiovascular (RCV) foram colesterol total 83 mg/dL (45 mg/dL), LDL-C 32 mg/ dL (<160 mg/dL), colesterol nao-HDL de 35 mg/dL, VLDL-C 3 mg/dL (<40 mg/dL), triglicerideos de 28 mg/dL, Apo-A1 112 mg/ dL (119-240 mg/dL), Apo B-100-25 mg/dL (40-125 mg/dL), us-PCR 1,47 mg/dL (<3 mg/dL) de Lp (a) 2 mg/dL (<30 mg/dL), homocisteina de 5,8 µmol/L (<15 µmol/L), a vitamina A 42 µg/dL (50-200 µg/dL), vitamina E 1051 µg/dL (50-180 µg/dL) e 25- (OH) D 48,9 ng/mL (30-54 ng/mL) em intervalos de normalidade. O HLA-27 foi negativo. Depois de encontrar achados bioquimicos de baixas concentracoes de lipoproteinas com apo-B, foi solicitado ao paciente um teste de saliva para estudo genetico de LipochipR para mutacoes no gene de Apo-B e PCSK9. Conclui-se que o paciente apresentou uma diminuicao na concentracao das lipoproteinas contendo Apo-B e triglicerideos. Os sintomas de dor abdominal e fezes pastosas apoiaram o diagnostico clinico. A inexistencia de deficit vitaminico, retardo mental, acantocitose e outros sintomas associados fez pensar numa heranca heterozigotica, que com as ferramentas disponiveis nao se pode descrever geneticamente ja que LipochipR nao detecta positividade para este paciente para uma mutacao de mudanca de aminoacidos no gene e exon de Apo 26, PCSK9-7, PCSK9- 4, PCSK9-10.

Serotonin 2A Receptor Gene Polymorphism in Korean Children with Attention-Deficit/Hyperactivity Disorder

OBJECTIVE: The purpose of this study was to investigate the association between the T102C polymorphism in the serotonin 2A receptor gene and attention-deficit/hyperactivity disorder (ADHD) in Korean patients. METHODS: A total of 189 Korean children with ADHD as well as both parents of the ADHD children and 150 normal children participated in this study. DNA was extracted from blood samples from all of the subjects, and genotyping was conducted. Based on the allele and genotype information obtained, case-control analyses were performed to compare the ADHD and normal children, and Transmission disequilibrium tests (TDTs) were used for family-based association testing (number of trios=113). Finally, according to the significant finding which was showed in the case-control analyses, the results of behavioral characterastics and neuropsychological test were compared between ADHD children with and without the C allele. RESULTS: In the case-control analyses, statistically significant differences were detected in the frequencies of genotypes containing the C allele (chi2=4.73, p=0.030). In the family-based association study, TDTs failed to detect linkage disequilibrium of the T102C polymorphism associated with ADHD children. In the ADHD children, both the mean reaction time and the standard deviation of the reaction time in the auditory continuous performance test were longer in the group with the C allele compared to the group without the C allele. CONCLUSION: The results of this study suggest that there is a significant genetic association between the T102C polymorphism in the serotonin 2A receptor gene and ADHD in Korean children.

Current Understanding in Neurobiology of Depressive Disorders: Imaging Genetic Studies on Serotonin Transporter

Depressive disorders have strong genetic components. However, conventional linkage and association studies have not yielded definitive results. These might be due to the absence of objective diagnostic tests, the complex nature of human behavior or the incomplete penetrance of psychiatric traits. Imaging genetics explores the influences of genetic variation on the brain function or structure. This technique could provide a more sensitive assessment than traditional behavioral measures in psychiatric studies. Imaging genetics is a relatively new field of psychiatric researches, and may improve our understanding on neurobiology of psychiatric disorders. In this review, current understanding in neurobiology of depressive disorders, especially imaging genetic studies on serotonin transporter will be discussed.

Enfermedad Celiaca en familiares de primer grado: Familia nuclear con 5 miembros afectados

La Enfermedad Celíaca (EC) se define como una enteropatía mediada inmunológicamente por una sensibilidad permanente al gluten en individuos genéticamente susceptible. Estudios epidemiológicos en América y Europa reportan una prevalencia aproximada entre 0,5 a 1% entre la población general. En los Estados Unidos solo de 10 a 15% o menos de estos individuos son diagnosticados y tratados. Existe una fuerte susceptibilidad genética en el desarrollo de EC, como lo confirma la elevada concordancia observada en gemelos monocigóticos, que llega hasta un 75%. Se encuentra una elevada prevalencia en familiares de primer y segundo grado que oscila entre 4-12%, esta relación es debida, en gran parte, a la existencia de una importante base genética condicionada por la presencia de antígenos de clase HLA-II (DQ2 y DQ8). Se presenta el caso de una familia nuclear constituida por 5 miembros, en la cual se lleva a cabo el screening para EC a partir de un caso índice, obteniendo como resultado que el 100% (5/5) del grupo familiar se encuentra positivo desde el punto de vista serológico para EC (Anticuerpos Anti TTG fracción Ig A), siendo necesario resaltar que el 40% de este grupo familiar se encuentra asintomático al momento del diagnostico, tanto desde el punto de vista gastrointestinal como no gastrointestinal. Consideramos, que es imperativo el estudio de las familias donde sea detectado al menos un caso de EC, debido a que la prevalencia de la penetración en un grupo familiar puede alcanzar hasta el 100%.

Celiac disease (CD) is an immune enteropathy mediated by a permanent sensitivity to gluten in genetically susceptible individuals. Previous studies in Europe and America reported prevalence estimated between 0.5 to 1% among the general population. In the United States only 10 to 15% or less of these individuals are diagnosed and treated. There is a strong genetic susceptibility in the development of CD, as confirmed by the high concordance observed in monozygotic twins, which reaches up to 75%. There is a high prevalence in first and second degree relatives that ranges between 4-12%; this relationship is due, in large part, to the existence of a significant genetic basis conditioned by the presence of HLA antigens class-II (DQ2 and DQ8). A case of a nuclear family consisting of 5 members was screened for CD from an index case, which resulted in 100% (5 / 5) of the family, was positive for serological CD (TTG Antibodies Ig fraction A). We have to address that 40% of this family are asymptomatic at diagnosis, both in terms of gastrointestinal and non gastrointestinal symptoms. We believe that the study of a family group in which at least one of the members is diagnosed with CD is imperative; due to the high prevalence level of household penetration CD, which can reach, up to 100%.

Genetic studies of allergic disease and their clinical implications / 대한내과학회지

Allergic disease is a complex disorder in which the interaction between environmental and genetic effects may modify both the susceptibility to and severity of the disease. Over the last few years, our understanding of the genetic basis of allergic diseases has improved markedly, which has led to the identification of several chromosome regions and loci showing linkage to allergic disease. As another approach, association studies between candidate gene polymorphisms and allergic diseases have been conducted in many areas and replicated in different ethnic groups. These approaches need to be followed by validation processes to confirm their functional relevance in the pathophysiology of allergic disease. This review updates genetic studies of and recent findings in, allergic disease.

Study Methods to Find Disease Genes in Complex Diseases / 대한류마티스학회지

Most common diseases are complex genetic traits. Identifying the genes that underlie the variation in the diseases has been challenging. Two major approaches have been used to map genetic variants that influence disease risk: linkage analysis and association study. Linkage analysis tests for the co-segregation of a marker and disease phenotype within a pedigree, whereas association study tests for differences in marker allele frequencies between patients and a control population. Linkage analysis is applied without any prior knowledge of the biological basis of the disease. In association study, genes with a known function with the potential to influence the disease phenotype are investigated for a direct role in disease. No single method is sufficient. A multi-strategy approach to the mapping of complex diseases is required. We review the different types of genetic studies to find genes for complex genetic traits.

Analysis of Comparative Genomic Hybridization in Pleomorphic Xanthoastrocytoma / 上海第二医科大学学报

Objective To detect genetic alterations in pleomorphic xanthoastrocytoma (PXA), and to investigate the mechanism of development of this neoplasm. Methods Three patients with PXA were studied. Comparative genomic hybridization (CGH) was performed to study chromosomal imbalances in PXA. Using immunohistochemical analysis, the expression of EGFR was detected in PXA. Results Using CGH analysis, genetic imbalance was detected on at least one chromosome for each case. One patient revealed multiple genetic alterations, including gains of 2p14-pter, 4p15-pter, 7p21-qter, 11q24-qter, 12 and 15q14-qter,as well as losses of 8p11.2-pter, 9p11-p23, 10p12-pter, and 13q14-qter. This patient experienced tumor recurrence and died one year later. Gain on Chromosome 7 and loss on Chromosome 8p were demonstrated in 2 of the 3 patients. Immunohistochemically, no EGFR positive reaction was found in all cases. Conclusion Detection of genetic alterations is very important in understanding the pathogenesis of PXA.

Progresses in genetic study of osteoporosis and the related problems:2007 update / 基础医学与临床

Great progresses were made in the genetic study of osteoporosis during the past decade.Genetic variants of endocrine hormones,bone matrix proteins and cytokines involved in bone metabolism were closely associated with bone mineral density,bone quality,bone structure,bone turnover rate or osteoporotic fracture.This paper is a comprehensive review of the most important and representative molecular genetic study in osteoporosis,and the important problems in osteoporosis molecular study.

The New Types of Informed Consent

Informed consent is an essential issue in medical practice. Recently, new types of informed consent have emerged from doctor-patient relationship. Genetic studies using patients' specimens are regulated by the "Bioethics and Biosafety Act", which mandates every genetic study be performed with given written informed consent. Clinical trials for drug development are regulated by the Korea Good Clinical Practice, which requires a review and approval process by the Institutional Review Board. Organ donation is regulated by the "Organ Donation Act". Informed consent from family members is important for organ donation of the deceased and minors. It is recommended that terminally ill patients have advance directives, but we do not have relevant legislation on this. New types of informed consent stress the justifiable intervention of the Parens Patriae and neutral third party. Along with the legalization, these should be summarized to prevent unnecessary conflicts.

Síndrome de Holt-Oram. Un caso clínico por mutación de novo

Introducción. El objetivo de este trabajo es informar el diagnóstico clínico del síndrome de Holt-Oram (SHO), el ecocardiográfico, el tratamiento neonatal endovascular y la cirugía cardiovascular. Caso clínico. Se informa un caso del SHO "por mutación de novo" en un lactante del sexo femenino con malformación ósea (MO); sindactilia en mano derecha, asociada con cardiopatía congénita (CC), hipoplasia de ventrículo derecho y estenosis pulmonar infundibular con persistencia del ducto arterioso y comunicación interauricular tipo ostium secundum. La mejoría neonatal fue obtenida por plastia endovascular de la arteria pulmonar. Al octavo mes de edad se realizó plastia del tracto de salida del ventrículo derecho; infundibular-anular, con buena evolución. Los antecedentes familiares en consanguíneos, 3 generaciones investigadas con MO y CC única o asociadas, fueron negativos. Se discute la importancia de genes, cromosomas y factores ambientales en la etiopatogenia del SHO por mutación de novo. Conclusión. La cirugía endovascular temprana y la "cardiocirugía electiva-paliativa", permiten en la actualidad una supervivencia en mejores condiciones clínicas y hemodinámicas con pronóstico vital a mediano y largo plazo más favorable.

Introduction. We inform the clinical and echocardiographic findings in a patient with Holt-Oram syndrome (HOS) and the evolution after treatment with cardiovascular surgery. Case report. It was a the novo clinic case of HOS, in a newborn girl with a bone malformation in the right hand, sindactilia in 2 fingers associated with congenital heart disease: hipoplasia of the right ventricle and lung arterial stenosis, with persistency of the arterial duct and interauricular communication type ostium secundum. The improvement in the newborn was obtained with endovascular plastia of the lung artery and palliative elective surgery at the 8 month of age. Conclusions. Early endovascular and palliative elective surgery permit a better prognosis in the infants with HOS.

Identification of G7304A Mutation in the Ryanodine Receptor Type 1 Gene in a Patient with Malignant Hyperthermia and an Extended Pedigree Study in a Korean Malignant Hyperthermia Family / 대한마취과학회지

BACKGROUND: Malignant hyperthermia (MH) is a disorder of the skeletal muscle manifested as a life threatening hypermetabolic crisis in susceptible individuals following exposure to inhalation anesthetics and depolarizing muscle relaxants. MH susceptibility (MHS) is inherited as an autosomal dominant trait and mutations in the gene encoding skeletal muscle ryanodine receptor (RYR1) are considered a common cause of the disorder. To date, more than 25 RYR1 mutations have been reported in families from Europe and North America. In Korea, however, little is known about the mutations in this candidate gene. METHODS: For the analysis of novel or previously published known RYR1 mutations in 13 exons of the RYR1 gene, PCR amplification and direct sequencing were performed in the proband. After identification of RYR1 mutation in the proband, we performed an extended pedigree study with informed consent from 160 members of a Korean MH family. DNA from 160 members of this family was screened for the presence or absence of RYR1 mutation identified in the proband. RESULTS: We identified a heterozygous G7304A mutation (Arg2435His) in exon 45 of the RYR1 gene in the proband. Six members of the family suffered fatal MH reaction and died. Two members including this proband had a fulminant MH episodes but survived. Two members of the family had presented with severe muscle hypotonia. PCR amplification for the screening of the site yields a fragment of 256 base pair (bp), which is fully cleaved into two fragments of 169 bp and 87 bp by Hga1 in normal individuals and 50% cleaved in individuals with a heterozygous mutation. We found the heterozygous G7304A mutation in 30 individuals from the 160 family members. CONCLUSIONS: This result is the first report to identify the mutation of RYR1 in patients with malignant hyperthermia in Korea. Further larger scale studies will provide important data regarding the frequency of occurrence of the RYR1 mutations in Korea and insight into the practicality of genetic screening relative to diagnosis of MHS and prevention of MH episodes and MH-related problems.