Clinical Characteristics Associated with Detected Respiratory Microorganism Employing Multiplex Nested PCR in Patients with Presumptive COVID-19 but Negative Molecular Results in Lima, Peru.

The COVID-19 pandemic circumstances have varied the pathogens related to acute respiratory infections (ARI), and most specialists have ignored them due to SARS-CoV-2's similar symptomatology. We identify respiratory pathogens with multiplex PCR in samples with presumptive SARS-CoV-2 but negative RT-qPCR results. We performed a retrospective transversal study employing clinical data and nasopharyngeal swab samples from patients with suspected clinical SARS-CoV-2 infection and a negative PCR result in a private laboratory in Lima, Peru. The samples were analyzed using the FilmArray™ respiratory panel. Of 342 samples, we detected at least one pathogen in 50% of the samples. The main ones were rhinovirus (54.38%), influenza A(H3N2) (22.80%), and respiratory syncytial virus (RSV) (14.04%). The clinical characteristics were sore throat (70.18%), cough (58.48%), nasal congestion (56.43%), and fever (40.06%). Only 41.46% and 48.78% of patients with influenza met the definition of influenza-like illness (ILI) by the World Health Organization (WHO) (characterized by cough and fever) and the Centers for Disease Control and Prevention (CDC) (characterized by fever and cough and sore throat), respectively. A higher prevalence of influenza was associated with ILI by WHO (aPR: 2.331) and ILI by CDC (aPR: 1.892), which was not observed with other respiratory viruses. The clinical characteristic associated with the increased prevalence of rhinovirus was nasal congestion (aPR: 1.84). For patients with ARI and negative PCR results, the leading respiratory pathogens detected were rhinovirus, influenza, and RSV. Less than half of patients with influenza presented ILI, although its presence was specific to the disease.

[Copy number variation and parental consanguinity elevated in newborns of high altitude with major congenital anomalies in Perú]. / Variantes en el número de copias y consanguinidad parental en neonatos de altura con anomalías congénitas en Perú.

Introduction: Congenital abnormalities could be caused by copy number variation or homozygous variants inherited of parental consanguineous. Purpose. Objetive: To show copy number variants and regions of homozygosity in neonates with malformative syndrome or one congenital anomaly major associated to facial dysmorphia or hypotonia. Methodology: Performed chromosomal microarray analysis (CGH/SNP) to 60 neonates with congenital anomalies born in Hospital Antonio Lorena and Hospital Regional Cusco. Results: 70% of the newborns had an abnormal test (n=42); 48,3% (n=29) patients had with regions of homozygosity above to 0,5% (endogamy coefficient up to 1/64). Pathogenic or likely pathogenic copy number variations with or without region of homozygosity were present in 14,2% (n=6) newborns with congenital abnormalities. We founded five patients with uncertain pathogenic copy number variations that have not been described previously and might correlate with phenotype. Conclusion: We founded a similar frequency of CNV in newborns with congenital abnormalities compared to previous reports. Nonetheless, parental consanguinity was increased compared to other countries of South America. This is the first report in Peru that showed to CMA as a useful diagnostic method in patients with congenital abnormalities and is pioneer in relation to other countries in Latinoamerica.

Introducción: Las variantes en el número de copias son un tipo de cambios en el genoma provocan anomalías congénitas. Objetivo: Determinar las variantes en el número de copias y el grado de consanguinidad parental en neonatos con síndromes malformativos o una anomalía congénita mayor asociado a dismorfia facial o hipotonía. Materiales y métodos: Se realizó el análisis cromosómico por micromatrices a 60 neonatos con anomalías congénitas evaluados en los Hospitales Antonio Lorena y Regional de Cusco. Resultados: Del total de pacientes estudiados, el 70% tuvo un resultado anómalo; de los cuales en el 14,2% de los recién nacidos se encontraron variantes en el número de copias patogénicas o probablemente patogénicas asociadas o no a regiones de homocigosidad que tuvieron relación con las anomalías congénitas descritas. En el 48,3% de los recién se encontró regiones de homocigosidad mayores a 0,5% (coeficiente de endogamia superior a 1/64). Por otro lado, encontramos cinco variantes en el número de copias de patogenicidad desconocida que no se han descrito anteriormente y podrían estar relacionadas con el fenotipo. Conclusión: Nuestra tasa de detección de las variantes en el número de copias está en relación con los reportes internacionales previos. Sin embargo, el porcentaje de neonatos con consanguinidad parental se encuentra por encima de lo reportado previamente, siendo superior a otras regiones de Sudamerica. Este es el primer reporte en el Perú, y es pionero en Latinoamérica al utilizar el análisis cromosómico por micromatrices en esta cohorte específica de pacientes.

Peruvian Newborn Male with 3p13 Deletion Syndrome Encompassing the FOXP1 Gene: Review of the Literature.

Copy number variation in loss of 3p13 is an infrequently reported entity characterized by hypertelorism, aniridia, microphthalmia, high palate, neurosensorial deafness, camptodactyly, heart malformation, development delay, autism spectrum disorder, seizures, and choanal atresia. The entity is caused probably by haploinsufficiency for FOXP1, UBA3, FAM19A1, and MITF. We report a newborn male with hypotonia, facial dysmorphism, heart malformation, and without clinical diagnosis; nevertheless, the use of appropriate genetic test, such us the chromosomal microarray analysis allowed identification of a copy number variant in loss of 5.5 Mb at chromosome 3 (p13-p14.1), that included 54 genes, encompassing FOXP1 gene. We compare the findings in our Peruvian patient to those of earlier reported patients; furthermore, add new signs for this entity.

Evaluation of mitogenome sequence concordance, heteroplasmy detection, and haplogrouping in a worldwide lineage study using the Precision ID mtDNA Whole Genome Panel.

The emergence of Massively Parallel Sequencing technologies enabled the analysis of full mitochondrial (mt)DNA sequences from forensically relevant samples that have, so far, only been typed in the control region or its hypervariable segments. In this study, we evaluated the performance of a commercially available multiplex-PCR-based assay, the Precision ID mtDNA Whole Genome Panel (Thermo Fisher Scientific), for the amplification and sequencing of the entire mitochondrial genome (mitogenome) from even degraded forensic specimens. For this purpose, more than 500 samples from 24 different populations were selected to cover the vast majority of established superhaplogroups. These are known to harbor different signature sequence motifs corresponding to their phylogenetic background that could have an effect on primer binding and, thus, could limit a broad application of this molecular genetic tool. The selected samples derived from various forensically relevant tissue sources and were DNA extracted using different methods. We evaluated sequence concordance and heteroplasmy detection and compared the findings to conventional Sanger sequencing as well as an orthogonal MPS platform. We discuss advantages and limitations of this approach with respect to forensic genetic workflow and analytical requirements.

From colorectal cancer pattern to the characterization of individuals at risk: Picture for genetic research in Latin America.

Colorectal cancer (CRC) is one of the most common cancers in Latin America and the Caribbean, with the highest rates reported for Uruguay, Brazil and Argentina. We provide a global snapshot of the CRC patterns, how screening is performed, and compared/contrasted to the genetic profile of Lynch syndrome (LS) in the region. From the literature, we find that only nine (20%) of the Latin America and the Caribbean countries have developed guidelines for early detection of CRC, and also with a low adherence. We describe a genetic profile of LS, including a total of 2,685 suspected families, where confirmed LS ranged from 8% in Uruguay and Argentina to 60% in Peru. Among confirmed LS, path_MLH1 variants were most commonly identified in Peru (82%), Mexico (80%), Chile (60%), and path_MSH2/EPCAM variants were most frequently identified in Colombia (80%) and Argentina (47%). Path_MSH6 and path_PMS2 variants were less common, but they showed important presence in Brazil (15%) and Chile (10%), respectively. Important differences exist at identifying LS families in Latin American countries, where the spectrum of path_MLH1 and path_MSH2 variants are those most frequently identified. Our findings have an impact on the evaluation of the patients and their relatives at risk for LS, derived from the gene affected. Although the awareness of hereditary cancer and genetic testing has improved in the last decade, it is remains deficient, with 39%-80% of the families not being identified for LS among those who actually met both the clinical criteria for LS and showed MMR deficiency.

[Lynch syndrome: genetic, clinical and diagnostic aspects]. / Síndrome de Lynch: aspectos genéticos, clínicos y diagnósticos.

This review aims to present the genetic, clinical and diagnostic aspects of Lynch syndrome, as well as providing the most relevant information about genetic counseling in these patients and the current recommendations for their surveillance.

[Cancer genetic counseling.] / Asesoría genética en cáncer.

La asesoría genética en cáncer permite reducir la morbimortalidad en pacientes con cáncer hereditario y sus familiares mediante un manejo multidisciplinario que establezca medidas preventivas, detección precoz y control de riesgos.

Síndrome de Lynch: aspectos genéticos, clínicos y diagnósticos / Lynch syndrome: genetic, clinical and diagnostic aspects

Esta revisión tiene como objetivo dar a conocer los aspectos genéticos, clínicos y diagnósticos del síndrome de Lynch, además de brindar la información más relevante acerca de la asesoría genética en estos pacientes y las recomendaciones actuales para su seguimiento.

This review aims to present the genetic, clinical and diagnostic aspects of Lynch syndrome, as well as providing the most relevant information about genetic counseling in these patients and the current recommendations for their surveillance.

[Familial medullary thyroid carcinoma: case report and literature review.] / Cáncer Medular de Tiroides familiar: reporte de un caso y revisión de la literatura.

Medullary thyroid carcinoma (MTC) is a malignant tumour of the calcitonin-secreting parafollicular C cells of the thyroid gland. Up to 25% of MTC are associated to pathogenic germinal variants on the proto-oncogene RET (locus 10q11.2), which cause Familial Medullary Thyroid Carcinoma (FMTC) or Multiple Endocrine Neoplasia type 2 (MEN2); genetic conditions inherited with autosomal dominant pattern. We present the first report of a Peruvian family with FMTC and a germinal pathogenic variant on RET proto-oncogene, identified with Sanger sequencing. This manuscript also shows a literature review of this hereditary cancer syndrome, where we highlight the relevance of primary prevention and the potential effect on public health in healthy carriers of germinal pathogenic variants.

El cáncer medular de tiroides (CMT) es un tumor maligno de las células C parafoliculares secretoras de calcitonina. Se estima que el 25% de los casos de CMT se asocian a variantes patogénicas a nivel de línea germinal en el protooncogen RET (locus 10q11.2), que son las causantes del desarrollo de Carcinoma Medular de Tiroides Familiar (CMTF) o de la Neoplasia Endocrina Múltiple tipo 2 (NEM2); condiciones genéticas con patrón de herencia autosómico dominante. Presentamos el primer reporte de una familia peruana con CMTF y con variante patogénica identificada a nivel de línea germinal en el gen RET, mediante secuenciamiento Sanger. Este manuscrito también muestra una revisión de la literatura de este síndrome hereditario oncológico, donde se resalta su importancia en la prevención primaria y potencial efecto en la salud pública en casos de portadores de variantes patogénicas germinales aparentemente sanos.

Síndrome de carcinoma de células basales nevoides (Síndrome Gorlin): reporte de dos casos y revisión de la literatura / Nevoid basal-cell carcinoma syndrome (Gorlin Syndrome): report of two cases and review of the literature

RESUMEN El síndrome Gorlin (SG) es una condición genética, con patrón de herencia autosómico dominante, con penetrancia completa y expresividad variable, debida a mutaciones germinales en los genes PTCH1 o SUFU, los cuales son componentes de la vía molecular Sonic hedgehog. El SG se caracteriza por la presencia de múltiples carcinomas de células basales nevoides, quistes odontogénicos, calcificación de la hoz del cerebro y lesiones en sacabocado en palmas y plantas. Este es el primer reporte de casos en el Perú sobre pacientes con SG, que cuentan con evaluación y asesoría genética. Presentamos dos casos de SG que cumplen criterios clínicos del síndrome y una revisión de la literatura.

ABSTRACT Gorlin syndrome (GS) is a genetic disorder with an autosomal dominant inheritance pattern, with complete penetrance and variable expressivity. GS is caused by germline mutations in the genes PTCH1 or SUFU, which are components of the Sonic hedgehog molecular pathway. GS is characterized by the presence of multiple nevoid basal cell carcinomas, odontogenic cysts, calcification of the brain sickle, and lesions in the palms and soles. This study is the first to report cases in Peru of patients with GS who underwent genetic evaluation and counseling. We present two GS cases that meet the clinical criteria for the syndrome and review the literature

A survey of the clinicopathological and molecular characteristics of patients with suspected Lynch syndrome in Latin America.

BACKGROUND: Genetic counselling and testing for Lynch syndrome (LS) have recently been introduced in several Latin America countries. We aimed to characterize the clinical, molecular and mismatch repair (MMR) variants spectrum of patients with suspected LS in Latin America. METHODS: Eleven LS hereditary cancer registries and 34 published LS databases were used to identify unrelated families that fulfilled the Amsterdam II (AMSII) criteria and/or the Bethesda guidelines or suggestive of a dominant colorectal (CRC) inheritance syndrome. RESULTS: We performed a thorough investigation of 15 countries and identified 6 countries where germline genetic testing for LS is available and 3 countries where tumor testing is used in the LS diagnosis. The spectrum of pathogenic MMR variants included MLH1 up to 54%, MSH2 up to 43%, MSH6 up to 10%, PMS2 up to 3% and EPCAM up to 0.8%. The Latin America MMR spectrum is broad with a total of 220 different variants which 80% were private and 20% were recurrent. Frequent regions included exons 11 of MLH1 (15%), exon 3 and 7 of MSH2 (17 and 15%, respectively), exon 4 of MSH6 (65%), exons 11 and 13 of PMS2 (31% and 23%, respectively). Sixteen international founder variants in MLH1, MSH2 and MSH6 were identified and 41 (19%) variants have not previously been reported, thus representing novel genetic variants in the MMR genes. The AMSII criteria was the most used clinical criteria to identify pathogenic MMR carriers although microsatellite instability, immunohistochemistry and family history are still the primary methods in several countries where no genetic testing for LS is available yet. CONCLUSION: The Latin America LS pathogenic MMR variants spectrum included new variants, frequently altered genetic regions and potential founder effects, emphasizing the relevance implementing Lynch syndrome genetic testing and counseling in all of Latin America countries.

[Nevoid basal-cell carcinoma syndrome (Gorlin Syndrome): report of two cases and review of the literature]. / Síndrome de carcinoma de células basales nevoides (Síndrome Gorlin): reporte de dos casos y revisión de la literatura.

Gorlin syndrome (GS) is a genetic disorder with an autosomal dominant inheritance pattern, with complete penetrance and variable expressivity. GS is caused by germline mutations in the genes PTCH1 or SUFU, which are components of the Sonic hedgehog molecular pathway. GS is characterized by the presence of multiple nevoid basal cell carcinomas, odontogenic cysts, calcification of the brain sickle, and lesions in the palms and soles. This study is the first to report cases in Peru of patients with GS who underwent genetic evaluation and counseling. We present two GS cases that meet the clinical criteria for the syndrome and review the literature.

El síndrome Gorlin (SG) es una condición genética, con patrón de herencia autosómico dominante, con penetrancia completa y expresividad variable, debida a mutaciones germinales en los genes PTCH1 o SUFU, los cuales son componentes de la vía molecular Sonic hedgehog. El SG se caracteriza por la presencia de múltiples carcinomas de células basales nevoides, quistes odontogénicos, calcificación de la hoz del cerebro y lesiones en sacabocado en palmas y plantas. Este es el primer reporte de casos en el Perú sobre pacientes con SG, que cuentan con evaluación y asesoría genética. Presentamos dos casos de SG que cumplen criterios clínicos del síndrome y una revisión de la literatura.

[Microsatellite instability in patients with diagnostic of colorectal cancer]. / Inestabilidad de microsatélites en pacientes con diagnóstico de cáncer colorrectal.

OBJECTIVE: To determine the presence of microsatellite instability in patients with colorectal cancer using the molecular panel Bethesda and discuss its significance in patients with suspected hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch Syndrome. MATERIALS AND METHODS: We worked with samples of peripheral blood and tumor tissue of 28 patients diagnosed with colorectal cancer referred to the Laboratory of Molecular Biology of the Instituto Nacional de Enfermedades Neoplasicas (INEN), Lima, with suspected of Lynch syndrome. DNA was extracted using kits of nucleic acid extraction of peripheral blood and paraffin-embedded tumor tissue. Five microsatellite markers of Bethesda panel were amplified: BAT25, BAT26, D2S123, D5S346 and D17S250, by polymerase chain reaction. IMS analysis was performed by electrophoresis on chip in the Bioanalyzer Agilent 2100. RESULTS: Of the patients studied, 11 had high IMS(IMS-H) and one could not be fully ranked, staying as MSI-H / IMS-L. In all cases of IMS-H both BAT26 and BAT25 were unstable. The IMS-H in these patients indicates high probability of HNPCC or Lynch syndrome; it must be contrasted with the genetic analysis of MMR genes. CONCLUSION: The technique allowed determine which patients have to continue with the study of system mismatch repair genes, for establish whether we facing to HNPCC or sporadic colorectal cancer.

[Lynch syndrome, Muir Torre variant: 2 cases]. / Síndrome de Lynch variante Muir-Torre: a propósito de 2 casos.

Lynch syndrome (LS) is an autosomal-dominant inherited cancer predisposition syndrome caused by germline mutations in DNA mismatch repair genes (MLH1, MSH2, MSH6 or PMS2). Muir-Torre syndrome (MTS) is a phenotypic variant of LS that includes a predisposition to sebaceous glands tumors and keratoacanthomas. We report two patients with MTS, with more than one LS-related cancer, skin lesions, family history of cancer andmicrosatellite instability and immunohistochemistry analysis.

Inestabilidad de microsatélites en pacientes con diagnóstico de cáncer colorrecta / Microsatellite instability in patients with diagnostic of colorectal cancer

Determinar la presencia de inestabilidad de microsatélites en pacientes con cáncer colorrectal usando el panel molecular Bethesda y discutir su importancia en pacientes con sospecha de cáncer colorrectal hereditario no polipósico (HNPCC) o con sospecha de síndrome de Lynch. Materiales y métodos: Se trabajó con muestras de sangre periférica y tejido tumoral de 28 pacientes con diagnóstico de cáncer colorrectal remitidos al laboratorio de Biología Molecular del Instituto Nacional de Enfermedades Neoplásicas (INEN) de Lima, bajo sospecha de Síndrome de Lynch. El ADN fue extraído utilizando kits de extracción de ácidos nucleicos para sangre periférica y tejido tumoral embebido en parafina. Se amplificaron los cinco marcadores microsatélites del panel Bethesda: BAT25, BAT26, D2S123, D5S346 y D17S250, por reacción en cadena de la polimerasa. El análisis de IMS fue realizado mediante electroforesis en chip en el bioanalizador Agilent 2100. Resultados: Del total de pacientes estudiados 11 tuvieron IMS alta (IMS-H) y uno no pudo ser totalmente clasificado quedando como IMS-H/IMS-L. En todos los casos de IMS-H tanto BAT25 como BAT26 resultaron inestables. La IMS-H en estos pacientes indica mayor probabilidad de HNPCC o síndrome de Lynch, lo cual debe ser contrastado con el análisis genético de los genes MMR. Conclusión: La técnica permitió determinar cuáles son los pacientes que deben continuar con el estudio de los genes del sistema de reparación de mal apareamiento del ADN, para establecer si estamos frente a casos de HNPCC o ante casos de cáncer colorrectal esporádicos...

To determine the presence of microsatellite instability in patients with colorectal cancer using the molecular panel Bethesda and discuss its significance in patients with suspected hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch Syndrome. Materials and methods: We worked with samples of peripheral blood and tumor tissue of 28 patients diagnosed with colorectal cancer referred to the Laboratory of Molecular Biology of the Instituto Nacional de Enfermedades Neoplasicas (INEN), Lima, with suspected of Lynch syndrome. DNA was extracted using kits of nucleic acid extraction of peripheral blood and paraffin-embedded tumor tissue. Five microsatellite markers of Bethesda panel were amplified: BAT25, BAT26, D2S123, D5S346 and D17S250, by polymerase chain reaction. IMS analysis was performed by electrophoresis on chip in the Bioanalyzer Agilent 2100. Results: Of the patients studied, 11 had high IMS (IMS-H) and one could not be fully ranked, staying as MSI-H / IMS-L. In all cases of IMS-H both BAT26 and BAT25 were unstable. The IMS-H in these patients indicates high probability of HNPCC or Lynch syndrome; it must be contrasted with the genetic analysis of MMR genes. Conclusion: The technique allowed determine which patients have to continue with the study of system mismatch repair genes, for establish whether we facing to HNPCC or sporadic colorectal cancer...

Síndrome de Lynch variante Muir-Torre: a propósito de 2 casos / Lynch syndrome, Muir Torre variant: 2 cases

El síndrome de Lynch (SL), es un síndrome genético con patrón de herencia autosómico dominante, que predispone el desarrollo de cáncer colorrectal y neoplasias extracolónicas, debido a la mutación germinal en alguno de los genes reparadores de los errores de la replicación del ADN (MLH1, MSH2, MSH6 o PMS2). El Síndrome de Muir-Torre (SMT), es una variante fenotípica del SL que predispone además a desarrollar tumores de glándulas sebáceas y queratoacantomas. Presentamos el caso de dos pacientes con SMT, con más de una neoplasia relacionada al SL, lesiones cutáneas, antecedentes familiares de cáncer y estudios de inestabilidad de microsatélites e inmunohistoquímica...

Lynch syndrome (LS) is an autosomal-dominant inherited cancer predisposition syndrome caused by germline mutations in DNA mismatch repair genes (MLH1, MSH2, MSH6 or PMS2). Muir-Torre syndrome (MTS) is a phenotypic variant of LS that includes a predisposition to sebaceous glands tumors and keratoacanthomas. We report two patients with MTS, with more than one LS-related cancer, skin lesions, family history of cancer andmicrosatellite instability and immunohistochemistry analysis...

Estado mutacional de los exones 19 y 21 de EGFR en adenocarcinoma de pulmón: Estudio en 122 pacientes peruanos y revisión de la evidencia de eficacia del inhibidor tirosina kinasa erlotinib / Mutational status of EGFR exons 19 and 21 in lung adenocarcinoma: Study in 122 peruvian patients and review of the efficacy of tyrosine kinase inhibitor erlotinib

Introducción: El cáncer de pulmón tiene altas tasas de incidencia y mortalidad, tanto en el país como en el mundo. El conocimiento de las alteraciones moleculares en esta neoplasia ha permitido desarrollar tratamientos individualizados, observándose resultados terapéuticos muy alentadores. El objetivo de este estudio fue determinar la frecuencia de mutaciones en los exones 19 y 21 en adenocarcinoma de pulmón en nuestra población y realizar una revisión de la evidencia de eficacia de erlotinib en pacientes con cáncer de pulmón de células no pequeñas. Métodos: Se recibieron 133 muestras consecutivas de adenocarcinoma de pulmón entre enero y octubre de 2011. El estado mutacional en el exón 19 de EGFR se realizó por el método de PCR convencional, con la técnica de enriquecimiento del alelo mutado. El estado mutacional en el exón 21 fue determinado mediante el análisis de la curva de desnaturalización por PCR en tiempo real. Resultados: El estado mutacional del exón 19 fue determinado en 122 muestras (11 muestras fueron no evaluables para este análisis, debido a falta de amplificación) y del exón 21 en 104 muestras (29 no fueron evaluables). La frecuencia de mutaciones en cualquiera de los exones fue del 39,3% (48 casos), en el exón 19 fue del 32% (39 casos), en el exón 21 fue de 8,7% (9 casos) y, simultáneamente, en ambos exones, en el 1,9% (2 casos). Conclusiones: Se detectaron una incidencia de mutaciones similares a otras poblaciones latinoamericanas. La evidencia clínica revisada de los estudios OPTIMAL y EURTAC muestra resultados alentadores.

Introduction: Lung cancer has a high incidence and mortality rates in this country as other countries. The knowledge of molecular disruptions in this neoplasm has permitted to develop individual treatments, observing therapeutic results very encouraging. The aim of this study was to establish the frequency of mutations of exons 19 and 21 in lung adenocarcinoma of our population and to make a review of the evidence of erlotinib’s efficacy in patients with non-small cell lung cancer. Methods: One hundred and thirty three consecutive samples of lung adenocarcinoma were received between January and October of 2011. The mutate state in the exon 19 of EGFR was made by the PCR conventional method with the enrichment technique of the mutated allele. The mutational state in exon 21 was set through the analysis of the melting curve by PCR in real time. Results: The mutational status of exon 19 was set in 122 samples (11 samples were non-evaluated for this analysis, due to the lack of amplification) and exon 21 in 104 samples (29 were non-evaluated). The frequency of mutations in any of the exons were 39.3% (48 cases), in the exon 19 was 32% (39 cases), in the exon 21 was 8.7% (9 cases) and simultaneity in both exons were 1.9% (2 cases). Conclusions: There was detected an incidence of mutation similar to other Latin American populations. Clinic evidence reviewed of studies Optimal and EURTAC show encouraged results.

Poblamiento del continente americano y del Perú sugerido de un análisis filogeográfico de haplogrupos del mtDNA en etnias nativas I: inferencias primarias / Peopling of the American continent and Peru as suggested from a phylogeographic mtDNA haplogroups analysis in native ethnoses. I: preliminary inferences

OBJETIVOS: Precisar el origen de las poblaciones peruanas en un contexto filogeográfico, global y temporal. METODOS: Análisis comparativo de los resultados obtenidos a partir del procesamiento del mtDNA, de cinco poblaciones peruanas nativas sitas en Pucallpa, Taquile, Anapia, Amantani y Los Uros, con los resultados obtenidos por diferentes autores en la misma molécula (reciente y antigua) de 91 etnias–localidades, que incluyen varias del continente americano y algunas de nuestro país, y 13 del SE del continente asiático. Realizamos un análisis filogeográfico a partir de las frecuencias de los haplogrupos hallados por RFLPs y una secINDEL del mtDNA. Los datos fueron procesados por el programa PHYLIP 3.65 opción Distancias de Reynolds, para determinar los valores F de Diferenciación Genética o Coalescencia. El algoritmo UPGMA usó los valores de F entre pares de ST STetnias–localidades, para construir un árbol de distancias que permita el análisis de sus principales grupamientos(clusters). RESULTADOS: El árbol obtenido exhibe 7 clusters. El cluster 1 comprende a la etnia Han ubicada al SEde Asia, en tanto que las americanas se ubican entre los clusters 2 al 7. Las etnias menos diversas fueron dos: la Quechua (Taquile, Puno-Perú) – 100 por ciento haplotipo B - y la de los Kuna (Panamá) – 100 por ciento haplotipo A-.CONCLUSIONES: Los mayores valores encontrados de diferenciación genética, corresponden a los Yanomami, con un F de 0.23741, mientras que en el Perú fueron los Quechua de Taquile con un valor F de 0.16673. En ambos casos los resultados indican, según la tabla de calificación de valores F , una Divergencia Genética Alta.

OBJETIVES: To determine the origins of Peruvian populations in a more global and temporal phylogeographic context. METHODS: mtDNA results obtained in our laboratories from the analysis of the mtDNA from 5 native Peruvian populations that inhabit Pucallpa, Taquile, Anapia, Amantani and Los Uros, were compared with the results obtained different authors on the same molecule from 91 ethnoses-localities that include some of our country, others from the American continent, as well as 13 of the SE of the Asian continent. Phylogeographic analysis was done from the haplogroups frequencies found from the RFLPs and an INDEL sequence of mtDNA, and the data were processed by the program PHYLIP 3.65, option Distances of Reynolds to find F values of Genetic ST Differentiation or Coalescency. The UPGMA algorithm allowed us to express the values F between pairs of ST ethnoses-localities and to carry out the analysis of the main clusters, by means of a tree. RESULTS: The tree exhibit 7 main clusters. Cluster I comprised only the ethnos located to SE of Asia. The American ethnoses are located along the clusters 2 to 7. The less diverse ones were two: the Quechua from Taquile, (Puno-Peru) - 100 per cent B haplotype, and the Kuna from Panama, – 100 per cent A haplotype. CONCLUSIONS: Genetic differentiation larger values were in the Yanomami (0.23741) group. For Peru, they were in the Aymara ethnos from Taquile with F values of 0.16673. Both correspond to a High Genetic Divergence respect to the near closest ones.