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Introducción. Las sorderas o hipoacusias prelinguales son de etiología genética entre el 60 y el 68% de los casos; de estos, del 20 al 40% son malformaciones del oído interno. De los casos de hipoacusia no sindrómica ligada al X se han descrito siete tipos. De las malformaciones de oído interno, la partición coclear incompleta tipo III es la menos frecuente.Objetivo. Presentar el reporte clínico-genético de una familia mexicana, con indi-viduos varones afectados por sordera neurosensorial congénita con malformación de oído interno. Material y Métodos. Se realizó estudio de una familia en la que nueve miembros presentaban sordera. Se estudiaron cuatro de ellos y una madre sin manifestaciones, a través del estudio clínico general por médico genetista, el estudio audiológico (otos-copía y audiometría) por médico audiólogo y el estudio de tomografía computada (TC) por médico radiólogo.Resultados. Los pacientes estudiados presentaron sordera neurosensorial congéni-ta, de severa a profunda bilateral. A través de la TC, se evidenció malformación de oído interno. Tres pacientes presentaron partición coclear incompleta tipo III y un paciente partición incompleta tipo I. Debido al estudio clínico y al árbol genealógico, se definió diagnóstico de hipoacusia neurosensorial no sindrómica ligada al X. La TC de la madre sin manifestaciones no presentó evidencia de malformaciones en oído interno (MOI).Conclusión. El estudio de imagen es fundamental para definir presencia o no de MOI en todos los pacientes con hipoacusia y así poder guiar la terapéutica y el aseso-ramiento genético, así como realizar los estudios moleculares más adecuados

Introduction. The pre-lingual deafness or hearing loss are of genetic cause in be-tween 60% and 68% of cases, among these, between 20% and 40% are malforma-tion of the inner ear. From the non-syndromic hearing loss cases that are linked to the X chromosome, seven types have been described. Among these inner ear malforma-tions, incomplete cochlear partition type III is the less frequent.Objective. Present the clinical genetical report of a Mexican family, with male in-dividuals affected by congenital neurosensory deafness with inner ear malformation.Materials and methodology. A study on a family in which nine members were affected by deafness was done. Four of them, plus a mother without manifestation, were studied through a general clinical study by a geneticist, an audiological study (otoscopy and audiometry) by an audiologist, and a computed tomography (CT) scan by a radiologist.Results. The studied patients presented congenital neurosensory deafness, from se-vere to deep bilateral. Via the CT, the inner ear malformation was made clear. Three of the patients presented incomplete cochlear partition type III and one patient in-complete cochlear partition type I. Due to the clinical study and the family tree, it was diagnosed non-syndromic neurosensory deafness linked to X. The CT of the mother without manifestation did not show evidence of inner ear malformations.Conclusion. The study by image is fundamental to define whether there is or not a presence of inner ear malformations in any patient with heading loss to be able to guide the therapeutics and the genetic counseling, as well as to make more accurate molecular studies

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OBJECTIVES: The genetics of sensorineural hearing loss is characterized by a high degree of heterogeneity. Despite this heterogeneity, DNA variants found within SLC26A4 have been reported to be the second most common contributor after those of GJB2 in many populations. METHODS: Whole exome sequencing and/or Sanger sequencing of SLC26A4 in 117 individuals with sensorineural hearing loss with or without inner ear anomalies but not with goiter from Turkey, Iran, and Mexico were performed. RESULTS: We identified 27 unique SLC26A4 variants in 31 probands. The variants c.1673A > G (p.N558S), c.1708-1G > A, c.1952C > T (p.P651L), and c.2090-1G > A have not been previously reported. The p.N558S variant was detected in two unrelated Mexican families. CONCLUSION: A range of SLC26A4 variants without a common recurrent mutation underlies SLC26A4-related hearing loss in Turkey, Iran, and Mexico.

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OBJECTIVE: We studied multi-loci variants to identify the contribution of six candidate genes (ADIPOQ, CDH13, LYPLAL1, MC4R, PPARG and PGC1A) in the development of obesity and overweight. DESIGN: We genotyped 404 chromosomes with eleven SNPs in Mexican female adolescents, who were subdivided into two groups (obesity-overweight and normal-weight) using the World Health Organization parameters. Genomic (800 chromosomes) and ancestral (208 chromosomes) controls were included to reduce the population bias. Anthropometric measurements, biochemical parameters, and caloric intake were obtained only in the groups of Mexican female adolescents. RESULTS: A positive genotype-phenotype association was found that involves the multi-allelic combination of three risk alleles (one in PPARG and two in LYPLAL1) with obesity and overweight (OR=3.1, P=.010). This combination also exhibited a significant association with waist circumference (P=.030) and triglycerides levels (P=.030). These associations were supported by a logistic regression analysis adjusted for several confounding variables. CONCLUSIONS: Our data suggest the joint participation of PPARG-LYPLAL1 genes in metabolic disorders development. Hence, these genes could act as potential biomarkers in obesity and overweight. Our findings underscore the complexity of metabolic disorders and provide evidence about the importance of multi-loci analysis to study complex diseases.

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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.

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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.

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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.

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Capillary electrophoresis (CE) may replace many conventional clinical laboratory methods, such as electrophoresis, Southern blotting, sequencing and HPLC (High-performance liquid chromatography). It is an ideal technique due to analytical speed, the possibility of handling great amount of samples, its capacity to separate small molecules according to their size, charge, hydrophobic and stereo-specificity its good reproducibility the use of small amounts of sample and reagents, its low costs and easy handling. The diagnosis of hereditary diseases or the predisposition to polygenic diseases related to specific mutations or polymorphisms can be carried out with this method. In clinical laboratories, this technique is being used for the analysis of several substrates present in urine or serum and for the diagnosis of some infectious agents. It is also a firsthand tool in forensic medicine for human identification and anthropology.

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Peripheral neuropathies include a wide range of pathological disorders characterized by damage of peripheral nerves. Among them, peripheral hereditary neuropathies are a group of frequent illnesses and early evolution. They have been named hereditary motor and sensory neuropathy (HMSN) or peripheral hereditary neuropathies type Charcot-Marie-Tooth (CMT). The most frequent types are CMT1, CMT2 and CMTX. Approximately 70% of the cases correspond to subtype CMT1A, associated with tandem duplication of a 1.5 Mb DNA fragment on chromosome 17p11.2-p12 that codifies the peripheral myelin protein PMP22. So far, there five different types of CMT (1,2,3,4,X) with approximately 32 subtypes, associated with more than 30 genes. Have been reported genetic heterogeneity and expression variability of the illness makes it necessary to carry on diagnostic strategies that integrate clinical study for determining genetic clinical history, family history, complete physical exploration, muscular strength, physical deformities, reflexes and sensitivity, and molecular studies allow detection of different types of mutations and help establish a correct diagnosis and an adequate genetic counseling.

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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.

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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.

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