Bone Remodeling and Bone Structural Genes in Legg-Calvé-Perthes Disease: The OPG rs2073618 and IL-6 rs1800795 Are Associated with High Risk in Mexican Patients.

Legg-Calve-Perthes disease (LCPD) is an idiopathic avascular necrosis of the pediatric femoral head. Bone remodeling and bone structural genes have the potential to contribute to the progression of LCPD when there is disequilibrium between bone resorption and bone formation. A case-control study was performed to search for associations of several common polymorphisms in the genes Receptor Activator for Nuclear Factor κappa B (RANK), Receptor Activator for Nuclear Factor κappa B Ligand (RANKL), osteoprotegerin (OPG), interleukin (IL)-6, and type 1 collagen (COL1A1) with LCPD susceptibility in Mexican children. A total of 23 children with LCPD and 46 healthy controls were genotyped for seven polymorphisms (rs3018362, rs12585014, rs2073618, rs1800795, rs1800796, rs1800012, and rs2586498) in the RANK, RANKL, OPG, IL-6, and COL1A1 genes by real-time polymerase chain reaction with TaqMan probes. The variant allele (C) of IL-6 rs1800795 was associated with increased risk of LCPD (odds ratio [OR]: 3.8, 95% confidence interval [CI]: [1.08-13.54], p = 0.033), adjusting data by body mass index (BMI) and coagulation factor V (FV), the association with increased risk remained (OR: 4.9, 95% CI: [1.14-21.04], p = 0.025). The OPG polymorphism rs2073618, specifically GC-GG carriers, was associated with a more than fourfold increased risk of developing LCPD (OR: 4.34, 95% CI: [1.04-18.12], p = 0.033) when data were adjusted by BMI-FV. There was no significant association between RANK rs3018362, RANKL rs12585014, IL-6 rs1800796, COL1A1 rs1800012, and rs2586498 polymorphisms and LCPD in a sample of Mexican children. The rs1800975 and rs2037618 polymorphisms in the IL-6 and OPG genes, respectively, are informative markers of increased risk of LCPD in Mexican children.

New Genetic Variants of RUNX2 in Mexican Families Cause Cleidocranial Dysplasia.

Cleidocranial dysplasia (CCD) is an autosomal dominant skeletal dysplasia characterized by persistent open skull sutures with bulging calvaria, hypoplasia, or aplasia of clavicles permitting abnormal opposition of the shoulders; wide public symphysis; short middle phalanx of the fifth fingers; and vertebral, craniofacial, and dental anomalies. It is a rare disease, with a prevalence of 1-9/1,000,000, high penetrance, and variable expression. The gene responsible for CCD is the Runt-related transcription factor 2 (RUNX2) gene. We characterize the clinical, genetic, and bioinformatic results of four CCD cases: two cases within Mexican families with six affected members, nine asymptomatic individuals, and two sporadic cases with CCD, with one hundred healthy controls. Genomic DNA analyses of the RUNX2 gene were performed for Sanger sequencing. Bioinformatics tools were used to predict the function, stability, and structural changes of the mutated RUNX2 proteins. Three novel heterozygous mutations (c.651_652delTA; c.538_539delinsCA; c.662T>A) and a previously reported mutation (c.674G>A) were detected. In silico analysis showed that all mutations had functional, stability-related, and structural alterations in the RUNX2 protein. Our results show novel mutations that enrich the pool of RUNX2 gene mutations with CCD. Moreover, the proband 1 presented clinical data not previously reported that could represent an expanded phenotype of severe expression.

Enlarging 18 F-FDG-Avid Solitary Pulmonary Nodule: A Distinctly Unusual Presentation of Cytomegalovirus Infection in a Patient Receiving Chemotherapy.

ABSTRACT: Rapidly growing lung lesions, particularly in immunocompromised patients, invoke consideration of an infectious etiology. Aspergillomas, for example, can appear as round nodules with soft tissue attenuation, often associated with cavitation, and are variably 18 F-FDG avid. In contrast, cytomegalovirus, which may also evidence 18 F-FDG uptake, typically manifests as ground-glass opacities, symmetrically distributed small pulmonary nodules, or confluent consolidations, with lower lobe predilection. We describe a patient treated for lymphoma presenting with a solitary enlarging FDG-avid lung nodule, which was determined on resection to be focal cytomegalovirus infection, a distinctly uncommon presentation of this pathogen, more typical of fungal or mycobacterial disease.

Localized Metastatic Recurrence of HCC following Distal Extremity Trauma: Bone Scintigraphy and Anatomicopathological Correlation.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer, with a poor median survival when left untreated. Extrahepatic metastases involving musculoskeletal tissues typically present with concomitant nonosseous metastases at the time of diagnosis. A 61-year-old male on 1-year remission, following transarterial chemoembolization of a 2.3-cm hepatic HCC 1 year before, presented with a 2-month history of left wrist pain and swelling after falling on an outstretched hand. Computed tomographic scan revealed diffuse osteolytic lesions localized in left hand and distal forearm, associated with equivocal diffuse activity on bone scan. Subsequent surgical debridement revealed metastatic hepatocellular carcinoma.

Sonographic characterization and surveillance of paravaginal smooth muscle tumor of uncertain malignant potential.

Sonographic characterization and surveillance of paravaginal smooth muscle tumor of uncertain malignant potential. (A1) Transvaginal ultrasound with probe placed over the right vaginal wall, showing a well-defined round mass with regular contours, a mostly hypoechoic and heterogeneous echotexture, and edge shadowing, deep to the right distal third of the right vagina. (A2) Multifrequency linear probe (9-14 MHz) placed over the right labium majus revealing hyperechoic striations (arrows on A1-A2) and central flow (arrowheads on A2). (B1) Resected solid white-tan mass of bland consistency. (B2) Hematoxylin-eosin microscopy (40X) showing fusiform cells, with mild to moderate atypia. (C1) Repeat transvaginal ultrasound six-years later showing a recurrent solid oval-shaped mass with regular contour, a mostly hypoechoic heterogeneous echotexture, and an anechoic area inside the solid mass (asterisk on C2) that could represent a focus of necrosis.

Association of Polymorphisms in Estrogen Receptor Genes (ESR1 and ESR2) with Osteoporosis and Fracture-Involvement of Comorbidities and Epistasis.

Single-nucleotide polymorphisms (SNPs) in the ESR1/ESR2 genes play a role in osteoporosis (OP). Our objective was to determine associations of polymorphisms in ESR genes with OP and fracture, SNP-SNP interactions, and involvement of comorbidities. We analyzed 170 Mexican osteoporotic women (FNOP), 173 with hip fracture (HFx), and 210 controls. The SNPs, ESR1 rs2234693CC, rs851982CC and rs1999805AA, were associated with reduced OP risk (odds ratios [ORs] = 0.35, 0.40 and 0.32, respectively; p < 0.05); rs2234693CC was associated with reduced fracture risk (OR = 0.24; p < 0.05). The obese/overweight carriers of rs9340799GG had a lower OP (OR = 0.15, p = 0.016) and fracture (OR = 0.12, p = 0.0057) risk. The rs9479055AA and rs3020404AA hypertensive carriers had a higher OP risk (OR = 5.96, p = 0.032; and OR = 5.29, p = 0.02, respectively). In addition, rs3020404AA had a higher risk of fracture (OR = 4.90, p = 0.045). The rs2228480GG hypertensive carriers had a higher risk of fracture (OR = 6.22, p = 0.0038). We found a synergic relation between the ESR1 rs3020331 and rs1999805 in femoral neck OP and HFx. The rs2234693 (PvuII) and rs9340799 (XbaI) polymorphisms are associated with a high risk forming a haplotype. The epistasis analysis suggests the contribution of both genes (ESR1/ESR2) to the risk of OP and fracture. Epistasis and involvement of obesity and hypertension lead to a significant modification of the risk.

Oncologic significance of unexpected osseous foci on FDG-PET without correlative CT abnormalities.

PURPOSE: Our purpose was to explore the clinical significance of unexpected osseous foci on 18F-FDG-PET without correlative CT abnormalities (FWCT) in patients referred for oncologic evaluation. The significance of FDG-avid foci without correlative CT abnormalities has been previously explored in tissues such as breast, lung, liver, and prostate; however, osseous foci without correlative CT abnormalities continue to present challenges in diagnostic interpretations. METHODS: This study is a retrospective review of 120 osseous FWCT, reported in 91 patients, and their corresponding clinical follow-up. We included only patients with at least 6 months of clinical follow-up leading to a final diagnosis, reviewing bone biopsy results, follow-up imaging, and clinical notes. We excluded those patients on active chemotherapy at the time of the scan. For reports describing > 3 foci, we only analyzed the one with highest maximum standardized uptake value (SUVmax). As a measure of uptake intensity, we obtained focus-to-liver ratios (F/L) utilizing their SUVmax and corresponding hepatic 3D SUVmean. RESULTS: Of 91 patients, 74 (81%) had biopsy-confirmed primary malignancies and 17 (19%) had suspicious findings on diagnostic imaging, but no proven primary malignancy. 50 of 120 (42%) osseous foci were malignant and 70 (58%) were benign. 49 of 120 (41%) foci were solitary and 71 (59%) were 0 with other foci (non-solitary). Malignancy resulted from 15/49 (31%) solitary foci and 35/71 (49%) non-solitary foci. Malignant lesions had a mean F/L 2.37 ± 0.397 and benign lesions a mean F/L 1.49 ± 0.169. Osseous malignancy correlated with a higher uptake intensity (Spearman = 0.408; P < 0.01) and was significantly associated with F/L ≥ 2.0 (P < 0.001). Osseous FWCT led to restaging and management modification in 12/91 (13%) patients. CONCLUSION: Osseous FWCT frequently represent early stages of malignancy. A higher index of suspicion is warranted for osseous FWCT associated with underlying myeloproliferative neoplasms, breast and lung cancer, and moderate (F/L 1.0-2.0) or high (F/L > 2.0) uptake intensity. Interpreting physicians encountering these variables can recommend interval follow-up with 18F-FDG-PET/CT or correlation with contrast-enhanced MRI or tissue biopsy. In patients with an altered biodistribution of 18F-FDG in the bone marrow (e.g., recent chemotherapy cycle), follow-up FDG-PET can be obtained at an appropriate time interval following oncologic treatment.

Biopelículas microbianas y su impacto en áreas médicas: fisiopatología, diagnóstico y tratamiento / Microbial biofilms and their impact on medical areas: physiopathology, diagnosis and treatment

Resumen Las biopelículas son comunidades de microorganismos que crecen agregados y rodeados por una matriz extracelular que ellos mismos producen, la cual favorece la adhesión covalente sobre superficies inertes y vivas; además, les ayuda a desarrollar alta tolerancia a las moléculas con actividad antimicrobiana. Por otra parte, las biopelículas se asocian con infecciones crónicas y persistentes que impactan de manera negativa en distintas áreas médicas. Además, generan altos costos a los sistemas de salud y a los pacientes cada año, porque son difíciles de tratar con antimicrobianos convencionales; adicionalmente, generan altas tasas de morbilidad y mortalidad. El objetivo de esta revisión es presentar información extensa y actualizada sobre el origen, la biosíntesis y la fisiopatología de las biopelículas, así como sobre su relación con infecciones crónicas, el diagnóstico, los tratamientos antimicrobianos actuales con actividad antibiopelícula y las perspectivas sobre la búsqueda de nuevos tratamientos. Estos últimos aún representan una importante área de investigación.

Abstract Biofilms are communities of microorganisms that grow aggregated and surrounded by an extracellular matrix, which they produce and favors them to adhere covalently to inert and living surfaces; it also helps them to develop high tolerance to molecules with antimicrobial activity. Moreover, biofilms are associated with chronic and persistent infections, which negatively impact different medical areas since they generate high costs to health care systems and patients every year because they are difficult to treat with conventional antimicrobial drugs. Additionally, they generate high rates of morbidity and mortality. The objective of this review was to present extensive and up-to-date information on the origin, biosynthesis, and pathophysiology of biofilms. Also, its relationship with chronic infections, diagnosis, current antimicrobial treatments with antibiotic activity, and perspectives on the search for new treatments, since the latter still represent an important area of research.

Revisión histórica de la prohibición de las drogas en Estados Unidos: desde los pilgrims hasta el Partido Prohibicionista / Historical review of the prohibition of drugs in the United States: from the pilgrims to the prohibitionist party

En este artículo se identifican las bases históricas del prohibicionismo hacia las drogas en Estados Unidos. Se propone que la negativa del empleo recreativo de las drogas no es exclusiva del siglo XX; en el caso de Estados Unidos es un proceso que se origina desde la llegada de los primeros colonos y tiene fundamento en la esfera religiosa protestante, en el desarrollo del capitalismo y más tarde en la oleada migratoria procedente de otras latitudes

This article describes the historical bases of the prohibition of drugs in the United States of America. It is proposed that the refusal to the recreational use of drugs is not unique to the twentieth century; in the American case is a process that originates from the arrival of the first settlers and in the protestant religious dogma, in the development of capitalism, and later in the migration wave

Characterization of a group unrelated patients with arthrogryposis multiplex congenita / Caracterização de um grupo de pacientes não relacionados com artrogripose múltipla congênita

ABSTRACT OBJECTIVE: Arthrogryposis multiplex congenita is a relatively rare neuromuscular syndrome, with a prevalence of 1:3000-5000 newborns. In this study, the authors describe the clinical features of a group of 50 unrelated Mexican patients with arthrogryposis multiplex congenita. METHODS: Patients were diagnosed by physical and radiographic examination and the family history was evaluated. RESULTS: Of the 50 cases, nine presented other features (pectum excavatum, cleft palate, mental retardation, ulnar agenesis, etc.). Environmental factors, as well as prenatal and family history, were analyzed. The chromosomal anomalies and clinical entities associated with arthrogryposis multiplex congenita were reported. No chromosomal aberrations were present in the cases with mental retardation. Three unrelated familial cases with arthrogryposis multiplex congenita were observed in which autosomal recessive, autosomal dominant and X-linked inheritance patterns are possible. A literature review regarding arthrogryposis multiplex congenita was also conducted. CONCLUSIONS: It is important to establish patient-specific physical therapy and rehabilitation programs. A multidisciplinary approach is necessary, with medical, surgical, rehabilitation, social and psychological care, including genetic counseling.

RESUMO OBJETIVO: A artrogripose múltipla congênita é uma síndrome neuromuscular relativamente rara, com prevalência de 1:3000-5000 recém-nascidos. É por isso que, neste estudo, descrevemos as características clínicas de um grupo de 50 casos de pacientes mexicanos não relacionados com artrogripose múltipla congênita. MÉTODOS: Os pacientes foram diagnosticados por exame físico e radiográfico e o histórico familiar foi avaliado. RESULTADOS: Descrevemos 50 pacientes não relacionados com artrogripose múltipla congênita. Nove deles apresentaram outras características (pectus excavatum, fissura palatina, retardo mental, agenesia da ulna etc.). Foram analisados os fatores ambientais, pré-natais e o histórico familiar. Relatamos as anomalias cromossômicas e as entidades clínicas associadas com a artrogripose múltipla congênita. Não havia aberração cromossômica nos casos com retardo mental. Também encontramos três casos familiares não relacionados com artrogripose múltipla congênita, em que são possíveis padrões de herança autossômica recessiva, autossômica dominante e ligada ao cromossomo X. Também analisamos a preocupação da literatura com a artrogripose múltipla congênita. CONCLUSÕES: Reiteramos a ideia de que é importante estabelecer programas de fisioterapia e reabilitação específicos para os pacientes. É necessária uma abordagem multidisciplinar com cuidado médico, cirúrgico, de reabilitação, social e psicológico, incluindo aconselhamento genético.

Risk Factors for Thrombosis Development in Mexican Patients.

BACKGROUND: To identify inherited factors: Protein C (PC), protein S (PS), antithrombin (AT), plasminogen (Plg), the activated PC resistance (APCR), prothrombin (PT) mutation G20210 A (PTG20210 A) and methylenetetrahydrofolate reductase C677 T polymorphism (MTHFR C677 T), as well as acquired-risk factors such as: diabetes mellitus, surgeries, smoking, obesity, hypertension, trauma, alcoholism, family history; and their association, in Mexican patients with diagnostic of thrombophilia. METHODS: Overall, 200 patients diagnosed with thrombophilia and 100 healthy controls. Commercial kits were used for the coagulometric tests and polymerase chain reaction, restriction fragment length polymorphism for molecular alterations. RESULTS: Alterations were found with an estimated prevalence to PC 0.65%, AT 2.04% and Plg 2.5%, APCR 2%, PT 20210 2%, and MTHFR 65%. The C677 T polymorphism of the MTHFR did not associate with acquired-risk factors so we can suppose that it is an independent risk factor. For the patients that only presented acquired-risk factors (21 of 200), the association smoking-alcoholism showed to be the cause of thrombosis with high risk. The following were also associated: smoking with AT, PC, and alcoholism; obesity with Plg; smoking with alcoholism, and PS deficiency. CONCLUSIONS: Risk factors for both primary and secondary and their association were present as a cause of thrombosis in the patients studied, and the possibility to suffer a recurrent thrombosis.

Anticoagulant proteins in a population of Mexican mestizo donors.

BACKGROUND: To determine the activity of antithrombin (AT), protein C (PC), and protein S (PS), as well as the frequency of deficiencies of these proteins in a population of healthy Mexican mestizo blood donors. METHODS: AT, PC, and PS were determined from 1,502 plasma samples of healthy blood donors by using commercial kits in a coagulometer 4 STA (Diagnostica Stago, Asnières, France). RESULTS: A total of 741 women and 761 men were under study. They were divided into age range groups (18-24, 25-34, 35-44, 45-54, and 55-64 years). Activity of AT, PC, and PS was determined. For AT, activity values were specific for each age group according to gender when it had to do with PS, as well as when PC was determined. Frequencies of AT, PC, PS, and activated PC resistance activity deficiencies were obtained from reference levels (RLs) and average levels of this study. Differences were found between both frequencies for AT, PC, and PS, and the average levels obtained were used in this study. The frequencies of the activity deficiencies obtained through the values gotten in this population were: AT, 0.6%; PC, 1.06% (which is higher than the one obtained using the RLs described by commercial kits 0.33% and 0.66%, respectively); and PS, 1% (which is less than 4.5%). CONCLUSIONS: It is necessary to know the characteristics and biological behavior of the coagulation proteins in the Mexican population because the RLs used have been established for populations that are genetically different.

Leiden V factor and spastic cerebral palsy in Mexican children.

AIM: Cerebral palsy (CP) is a persistent motor disorder that appears before the patient is 3 years old due to a nonprogressive interference in the brain's development which takes place before the central nervous system growth is complete. Causes of this have been studied, and one that has been proposed for spastic hemiparesis CP is the Leiden mutation of V factor coagulation. We want to know whether this mutation can cause CP in our population. MATERIALS AND METHODS: We carried out a study of cases and controls with 94 patients with spastic hemiparesis CP and 120 controls as well as their mothers with their controls. RESULTS: None of the patients, their mothers, or controls had the Leiden mutation; however, other risk factors were significant: hypoxia odds ratio (OR) 7.189 (2.546, 20.302) p=0.0001, smoking OR 16.621 (2.945, 93.818) p=0.001, maternal infections (urinary or vaginal) OR 7.040 (2.952, 16.789) p=0.0001, weeks of gestation OR 0.866 (0.7750, 0.999) p=0.048, and maternal age OR 1.114 (1.031, 1.204) p=0.006. CONCLUSION: Leiden mutation of factor V is not an important factor for our Mexican mestizo population; however, there are other important perinatal risk factors.

Asociación de la RPCA con mutaciones Leiden y Cambridge del factor V de la coagulación en pacientes mexicanos con trombofilia primaria / Association of resistance to activated protein with the presence of Leiden and Cambridge Factor V mutations in Mexican patients with primary thrombophilia

Introducción: Las mutaciones Leiden y Cambridge del factor V de la coagulación y la resistencia a la proteína C activada (RPCA) son alteraciones que se relacionan con trombosis venosa y arterial. En este trabajo se analizó si la RPCA está asociada con las mutaciones Leiden y Cambridge, y la frecuencia de éstas en población mestiza mexicana. Material y métodos: Se incluyeron 150 pacientes mexicanos con trombofilia primaria y 100 sujetos sanos. Se determinó la RPCA empleando método comercial y los genotipos factor V Leiden y factor V Cambridge mediante PCR-RFLPs. Resultados: La RPCA fue positiva en cuatro pacientes y en un individuo control; sin embargo, no se encontró la mutación Leiden o Cambridge en la población estudiada, por lo que la RPCA no se correlacionó con ninguna de las mutaciones investigadas. Conclusiones: Los resultados indican que existen otras causas primarias o secundarias diferentes a las analizadas, que condicionan la RPCA. Además, la frecuencia obtenida para la RPCA en nuestra población trombofílica mestiza mexicana fue menor comparada con la obtenida en población caucásica, quizá por tratarse de poblaciones genéticamente diferentes.

BACKGROUND: Leiden and Cambridge factor V coagulation mutations and activated protein C resistance (RaPC) are alterations related with vein and artery thrombosis. In this study we aimed to determine whether RaPC is associated with the presence of Leiden and Cambridge mutation and the frequency of these mutations in the racially mestizo Mexican population. METHODS: We included 150 Mexican patients with primary thrombophilia and 100 healthy subjects in this study. RaPC was determined using commercial methods and genotypes FV Leiden and FV Cambridge with PCR-RFLPs. RESULTS: RaPC was positive in four patients and in one control individual; however, there was no presence of Leiden or Cambridge mutation in the studied group; thus, RaPC was not correlated with the presence of any of the studied mutations. CONCLUSIONS: These results indicate that there are other primary or secondary causes different from those studied, which condition the presence of RaPC. Furthermore, the frequency obtained for RaPC in our thrombophilic population of racially mixed Mexicans is lower compared to that obtained in the Caucasian population, most probably because they are genetically different populations.

Diseño de microsondas mediante hibridación virtual para el estudio de variantes en los sitios REP-CMT1A / Microarray design using virtual hybridization to study variations in REP-CMT1A sites

Antecedentes: El gen PMP22 se encuentra duplicado en pacientes con Charcot-Marie-Tooth 1A (CMT1A); se ha descrito que el origen de la duplicación es el intercambio desigual de las cromátidas durante la meiosis entre dos regiones de 24 kb denominadas sitios REPCMT1A, encontrándose un REP proximal y un REP distal, los cuales tienen una homología de 98%. Dentro de cada uno de estos sitios existen zonas denominadas puntos calientes de mutación (hot spot), donde se presenta el mayor número de variantes y mutaciones que pudieran dar origen al intercambio desigual. El objetivo de este trabajo fue diseñar un conjunto de microsondas para elaborar un microarreglo con el cual pueda detectarse la presencia de variantes y puntos de mutación en los sitios REP-proximal y REP-distal CMT1A. Material y métodos A partir de las secuencias informadas de los REP distal y proximal, se delimitaron los sitios hot spot dentro de las regiones proximal y distal. Estas secuencias se alinearon, se empalmaron y se detectaron 12 zonas de diferencia secuencial. Resultados y conclusiones. Se diseñaron y analizaron 24 microsondas mediante el programa Genosensor Probe Designer. Las sondas podrán ser sintetizadas y utilizadas en un microarreglo que permita encontrar variaciones, puntos de mutación, y facilitar el diagnóstico de pacientes con CMT1A.

BACKGROUND: Gene PMP22 is duplicated in patients with CMT1A. Duplication is due to an unequal chromatid interchange during meiosis that takes place between two 24 Kb regions named REP-CMT1A proximal and distal sites. Homology is approximately 98%. Within each one of the sites we find zones termed hot spots where a greater number of variants and mutations could give origin to an unequal interchange. The aim of this study was to design a set of probes to create a microarray that could detect the presence of variants and mutation points in distal and proximal REP sites among patients with CMT1A. MATERIAL AND METHODS: With reported sequences of distal and proximal REPs, we determined hot spot sites within proximal and distal regions. These sequences were aligned and matched, hence 12 zones were detected. RESULTS AND CONCLUSIONS: Twenty four probes were designed and analyzed using the Genosensor Probe Designer program. Probes could be synthesized and used in a microarray that is able to find variations and mutation points and facilitates diagnosis of patients with CMT1A.

Estrategias para el diagnóstico clinico y molecular de Charcot-Marie-Tooth 1A: estudio en pacientes mexicanos / Strategies for clinical and molecular diagnosis of Charcot-Marie-Tooth 1A among Mexican patients

Antecedentes: La neuropatía periférica de Charcot-Marie-Tooth (CMT) es la enfermedad hereditaria más común del sistema nervioso periférico humano. El subtipo más frecuente, CMT1A, es asociado a una duplicación de un fragmento de ~1.5 Mb en 17p11.2-p12, que incluye al gen PMP22. Objetivo: Describir diferentes estrategias para el diagnóstico clínico y molecular de CMT1A en pacientes del Instituto Nacional de Rehabilitación. Material y métodos: A 17 pacientes estudiados clínica y electrofisiológicamente que reunieron los criterios para CMT1, se les realizó el estudio molecular mediante electroforesis capilar para detectar la duplicación del gen PMP22. Resultados: Los estudios clínico, bioquímico y electrofisiológico ofrecieron los criterios para establecer el diagnóstico de CMT1. Con la electroforesis capilar se detectó la duplicación del gen PMP22 en siete pacientes que fueron diagnosticados clínica y electrofisiológicamente como CMT1, pudiendo llegar al diagnóstico de CMT1A. Todas las duplicaciones identificadas fueron corroboradas mediante hibridación in situ fluorescente. Conclusión: Los resultados nos permiten asegurar que la electroforesis capilar es un método fácil y confiable para detectar la duplicación del gen PMP22. Además, el aplicar diferentes estrategias tanto clínicas, electrofisiológicas y moleculares en este tipo de pacientes, nos permitieron establecer el diagnóstico correcto y ofrecer asesoramiento genético adecuado.

BACKGROUND: Charcot-Marie-Tooth (CMT) is the most common inherited disorder of the human peripheral nerve. The mos tfrequent subtype, CMT1A, is associated with duplication of approximately 1.5 Mb fragment in 17p11-p12, that includes the PMP22 gene. OBJECTIVE: The aim of this study was to describe different strategies used for clinical and molecular CNT1A diagnoses among patients attending the National Rehabilitation Institute of Mexico (INR). MATERIAL AND METHODS: 17 patients had clinical and electrophysiological features compatible with CMT1. A molecular study using capillary electrophoresis (CE) was performed and a PMP22 gene duplication was detected RESULTS: Clinical, biochemical and electrophysiological studies constituted the inclusion criteria to establish a CMT1 diagnosis. With CE the duplication of the PMP22 gene was observable and we established a possible CMT1A diagnosis in seven patients. All duplications detected by capillary electrophoresis were corroborated using FISH. CONCLUSION: CE is a feasible and reliable method to detect PMP22 gene duplication. Using different clinical, electrophysiological and molecular strategies in this patient population allowed us to establish an accurate diagnosis and offer suitable genetic counseling.

Dopaje genético: transferencia génica y su posible detección molecular / Gene doping: gene transfer and possible molecular detection

El uso de sustancias prohibidas en el deporte con el propósito de incrementar el rendimiento en las competencias deportivas ha provocado que los organismos internacionales en el ámbito deportivo, como el COI y la WADA, traten de tomar medidas en contra del dopaje. Uno de los métodos más recientes de dopaje es el denominado dopaje genético, definido como el uso no terapéutico de genes, elementos genéticos y/o células que tienen la capacidad de incrementar el rendimiento atlético. Ahora bien, el dopaje genético no es fácil de detectar y puede tener consecuencias graves. Es necesario usar técnicas de biología molecular para conocer la diferencia entre un genoma “normal” y un genoma “alterado”, desarrollar métodos analíticos y moleculares en los laboratorios de control del dopaje y trabajar en políticas apropiadas para evitar el uso no terapéutico de genes.

The use of illegal substances in sports to enhance athletic performance during competition has caused international sports organizations such as the COI and WADA to take anti doping measures. A new doping method know as gene doping is defined as [quot ]the non-therapeutic use of genes, genetic elements and/or cells that have the capacity to enhance athletic performance[quot ]. However, gene doping in sports is not easily identified and can cause serious consequences. Molecular biology techniques are needed in order to distinguish the difference between a [quot ]normal[quot ] and an [quot ]altered[quot ] genome. Further, we need to develop new analytic methods and biological molecular techniques in anti-doping laboratories, and design programs that avoid the non therapeutic use of genes.

Incontinentia pigmenti (IP2): familiar case report with affected men. Literature review.

UNLABELLED: Incontinentia pigmenti is a genodermatosis described by Garrod and in 1920 by Bloch, Sulzberger, Siemens y Bardach. It is an ectodermic disorder that affects skin, teeth, eyes and may also have neurological problems. The IP2 name describes the histological characteristics, the incontinence of melanin into the melanocytes cells in the epidermal basal layer and its presence in superficial dermis. IP2 is an x-linked dominant condition but genetic heterogeneity may exist. CASE REPORT: The patient was 4 yrs 5 months old when she came for the first time. In a physical exploration she presented sparse and thin hair, eyelashes and eyebrows, beaked nose, labial protrusion, the four central teeth have a conic crown and there was also a delayed eruption of other teeth, right eye strabismus, hipoacusia, language defects and a trunk, legs, feet, and face dermatosis characterized by grouped vesicles, hyperkeratotic and warty lesions and brownish-gray lesions in a lineal pattern. The patient s father had hypopigmented lesions in the posterior regions of both legs. The oral clinical and radiographic exams showed diverse anomalies. Both the patient's and the father's chromosomal studies were normal. DISCUSSION: In the present case we can see that the father has IP2 without supernumeraries X, with the antecedent that his mother had something similar. It is possible that the inheritance was autosomic dominant or it is a different mutation of NEMO (NF-kappa-B essential modulator) gene to a classical one, which was found in some affected men. It is necessary to carry out a molecular study of these patients.