Avances en el diagnóstico de la enfermedad granulomatosa crónica: primer estudio familiar en Cuba / Advances in the diagnosis of chronic granulomatous disease: the first family study in Cuba

Introducción: La enfermedad granulomatosa crónica es una inmunodeficiencia primaria causada por mutaciones en la enzima NADPH oxidasa. Esta compromete la producción de especies reactivas del oxígeno, que son importantes contra patógenos. La prueba de la oxidación de la dihidrorodamina es un método eficaz para diagnosticar la enfermedad. Objetivo: Demostrar la utilidad de la prueba de la oxidación de la dihidrorodamina y del patrón de herencia en la confirmación del diagnóstico de la enfermedad granulomatosa crónica de un paciente. Métodos: Estudio de caso de una familia con diagnóstico de enfermedad granulomatosa crónica. Se tomó muestra de sangre periférica para citometría de flujo a tres individuos. Se realizó la prueba de la oxidación de la dihidrorodamina bajo estímulo con acetato de forbolmiristato y se evaluaron las subpoblaciones linfocitarias. Las muestras se leyeron en un citómetro GALLIOS, Beckman Coulter. Los datos obtenidos se analizaron en el programa informático Kaluza. Resultados: El paciente masculino tuvo un valor de oxidación de la dihidrorodamina positiva de 0,87 por ciento, que confirmó un patrón de herencia ligado al cromosoma X; mientras que la madre y hermana gemela portadoras tuvieron valores de 46,76 por ciento y 37,32 por ciento, respectivamente. Se encontraron alteraciones en las subpoblaciones linfocitarias. Conclusiones: La prueba de la oxidación de la dihidrorodamina es un método muy efectivo, rápido y sencillo que confirma el diagnóstico de la enfermedad granulomatosa crónica y determina el patrón de herencia y fenotipo de la enfermedad. Además, permite identificar a las mujeres portadoras según la distribución de los neutrófilos normales y los que tienen el gen CYBB mutado(AU)

Introduction: Chronic granulomatous disease is a primary immunodeficiency caused by mutations in the NADPH oxidase enzymes. This compromises the production of oxygen reactive species, which are important against pathogens. The dihydrorhodamine oxidation test is an effective method for diagnosing the disease. Objective: To demonstrate the usefulness of the dihydrorhodamine oxidation test and the inheritance pattern in confirming the diagnosis of chronic granulomatous disease in a patient. Methods: A case study of a family with a diagnosis of chronic granulomatous disease. A peripheral blood sample was taken from three individuals and by flow cytometry. The dihydrorhodamine oxidation test was performed under stimulation with phorbolmyristate acetate, and lymphocyte subpopulations were evaluated. The samples were read on a GALLIOS, Beckman Coulter cytometer. The data obtained were analyzed using the computer program Kaluza. Results: The male patient had a positive dihydrorhodamine oxidation value of 0.87 percent, which confirmed an inheritance pattern linked to the X chromosome; while the carrier mother and twin sister had values 8203;8203;of 46.76 percent and 37.32 percent, respectively. Alterations were found in the lymphocyte subpopulations. Conclusions: The dihydrorhodamine oxidation test is a very effective, fast and simple method that confirms the diagnosis of chronic granulomatous disease and determines the inheritance pattern and phenotype of the disease. In addition, it allows the identification of female carriers according to the distribution of normal neutrophils and those with the CYBB mutation(AU)

A pioneering RET genetic screening study in the State of Ceará, Brazil, evaluating patients with medullary thyroid cancer and at-risk relatives: experience with 247 individuals

ABSTRACT Objective: Initial diagnosis of medullary thyroid carcinoma (MTC) is frequently associated with advanced stages and a poor prognosis. Thus, the need for earlier diagnoses and detection in relatives at risk for the disease has led to increased use of RET genetic screening. Subjects and methods: We performed RET screening in 247 subjects who were referred to the Brazilian Research Consortium for Multiple Endocrine Neoplasia (BRASMEN) Center in the State of Ceará. Direct genetic sequencing was used to analyze exons 8, 10, 11, and 13-16 in MTC index cases and specific exons in at risk relatives. Afterward, clinical follow-up was offered to all the patients with MTC and their affected relatives. Results: RET screening was performed in 60 MTC index patients and 187 at-risk family members. At the initial clinical assessment of the index patients, 54 (90%) were diagnosed with apparently sporadic disease and 6 (10%) diagnosed with hereditary disease. After RET screening, we found that 31 (52%) index patients had sporadic disease, and 29 (48%) had hereditary disease. Regarding at-risk relatives, 73/187 were mutation carriers. Mutations in RET codon 804 and the rare p.M918V mutation were the most prevalent. Conclusions: Performing RET screening in Ceará allowed us to identify a different mutation profile in this region compared with other areas. RET screening also enabled the diagnosis of a significant number of hereditary MTC patients who were initially classified as sporadic disease patients and benefited their relatives, who were unaware of the risks and the consequences of bearing a RET mutation.

Hemofilia: aspectos históricos y genéticos / Hemophilia: historical and genetic aspects

La hemofilia es un trastorno hemorrágico con disminución o ausencia de la actividad procoagulante del factor VIII o del IX. Las primeras descripciones de esta enfermedad son tan antiguas como la propia humanidad. A lo largo de los años, la hemofilia ha sido nombrada enfermedad real debido a que la padecieron diversos miembros de las familias reales europeas. En la actualidad, mediante estudios moleculares, se encontró el defecto genético causante de la enfermedad en los varones hemofílicos de la familia de la Reina Victoria y se encontró que sus descendientes padecieron una hemofilia B severa. El fenotipo de esta enfermedad es hemorrágico; se observan sangramientos en diversos sitios de la economía condicionados fundamentalmente por los niveles del factor deficiente. Existen otros factores que intervienen en las características fenotípicas variables de estos pacientes, entre ellos: las características intrínsecas de los factores VIII/IX, la presencia de genes modificadores y factores ambientales que influyen sobre la severidad de la enfermedad. Se revisa la correlación genotipo-fenotipo en esta enfermedad mediante las mutaciones más frecuentes en cada tipo de hemofilia. En cuanto a la presencia de los inhibidores, se destacan las evidencias actuales en relación con los factores de riesgo relacionados con su aparición y los aspectos moleculares presentes en la variante de hemofilia B Leyden

Hemophilia is a hemorrhagic disorder characterized by decreasing or absence of the procoagulant activity in factor VIII or IX. First descriptions of this disease are as old as mankind itself. During time, hemophilia has been called royal disease since different members of European royal families suffered from it. Currently, by molecular studies, it was found the causing genetic defect of this disease in hemophilic male members of Queen Victoria´s family; and it was found that her descendants suffered a severe hemophilia B. This disease phenotype is hemorrhagic; bleeding in different sites is observed which are mainly conditioned by the levels of the deficient factor. There are other factors participating in the variable phenotype characteristic of these patients, such as: intrinsic characteristics of factors VIII/IX, the presence of modifying genes and environment factors which influence on this disease severity. It is revised here the correlation genotype-phenotype in this disease through the most frequent mutations in each type of hemophilia. Concerning the presence of inhibitors, it is highlighted the current evidences in relation with risk factors related to its emergence and molecular aspects present in hemophilia variant B Leyden

Invasive & non-invasive approaches for prenatal diagnosis of haemoglobinopathies: Experiences from India.

The thalassaemias and sickle cell disease are the commonest monogenic disorders in India. There are an estimated 7500 - 12,000 babies with β-thalassaemia major born every year in the country. While the overall prevalence of carriers in different States varies from 1.5 to 4 per cent, recent work has shown considerable variations in frequencies even within States. Thus, micromapping would help to determine the true burden of the disease. Although screening in antenatal clinics is being done at many centres, only 15-20 per cent of pregnant women register in antenatal clinics in public hospitals in the first trimester of pregnancy. There are only a handful of centres in major cities in this vast country where prenatal diagnosis is done. There is considerable molecular heterogeneity with 64 mutations identified, of which 6 to 7 common mutations account for 80-90 per cent of mutant alleles. First trimester foetal diagnosis is done by chorionic villus sampling (CVS) and DNA analysis using reverse dot blot hybridization, amplification refractory mutation system (ARMS) and DNA sequencing. Second trimester diagnosis is done by cordocentesis and foetal blood analysis on HPLC at a few centres. Our experience on prenatal diagnosis of haemoglobinopathies in 2221 pregnancies has shown that >90 per cent of couples were referred for prenatal diagnosis of β-thalassaemia after having one or more affected children while about 35 per cent of couples were referred for prenatal diagnosis of sickle cell disorders prospectively. There is a clear need for more data from India on non-invasive approaches for prenatal diagnosis.

Análisis de las inversiones del intrón 1 y 22 y secuenciación del gen F8 para el diagnóstico genético-molecular de hemofilia A en Chile / Introns 1 and 22 inversions and F8 gene sequencing for molecular diagnosis of hemophilia A in Chile

Background: Hemophilia A is an inherited disorder caused by alterations in factor VIII gene (F8) located on the X-chromosome, the intron 22 inversion being the most common mutation. The rest are predominantly point mutations distributed along this large gene of 26 exons. Aim: To implement a molecular diagnostic test to detect mutations in the F8 gene in Chilean patients with Hemophilia A. Material and Methods: To validate the testing methods, we analyzed samples with intron 22 and intron 1 inversion, and with point mutations previously studied, as well as one subject without Hemophilia. We also studied unrelated Chilean patients with Hemophilia A and their female relatives for carrier testing. Intron 22 and intron 1 inversions were studied by long distance polymerase chain reaction (PCR) and point mutations by sequencing the coding and promoter regions of the F8 gene. Results: The results obtained in all samples used for validation were concordant with those obtained previously. In the Chilean patients, the intron 22 inversion and point mutations previously described were observed. In 6 out of 9 patients with mild Hemophilia A we found the same mutation (Arg2159Cys) in exon 23, which has been described as prevalent in mild Hemophilia A. Conclusions: The analysis of intron 22 and intron 1 inversions, as well as of point mutations in the F8 gene will help us to confirm the diagnosis in patients with severe, moderate and mild Hemophilia A, and also it will allow us to perform carrier testing and to provide better genetic counseling.

Estudio familiar de las hemofilias A y B: 5 años de experiencia en la detección de portadoras / Family study of hemophilia A and B: 5 years of experience in carrier detection

La hemofilia se caracteriza por ser una enfermedad congénita del trastorno de la coagulación y constituye un desorden recesivo ligado al cromosoma X. El estudio molecular se realiza por estudios indirectos por ser causada por mutaciones heterogéneas en los genes del FVIII y FIX. Se realizó el estudio de 40 familias afectadas con hemofilia A (HA) y 10 hemofilia B (HB). La extracción de ADN se realizó por el método de precipitación salina a 293 muestras de sangre y 19 de líquido amniótico, y se hizo el análisis de los polimorfismos St14, Bcl I y Hind III para la HA y Taq I, Xmn I y Dde I para la HB. Se usó la técnica de PCR. En el caso de la HA se obtuvo el 35 por ciento de informatividad para St14 y Hind III y 32,5 para Bcl 1. El polimorfismo Dde I fue el más informativo para la HB con el 33 por ciento; mientras que Taq I representó el 10 por ciento de informatividad y XmnI el 0 por ciento. Se comprobó que de las 40 familias analizadas con HA, 23 fueron informativas. Por otra parte, fueron informativas 4 familias de las afectadas con HB. Se realizaron 19 diagnósticos prenatales con previa determinación del sexo fetal, incluidos 3 varones enfermos

Hemophilia is a congenital disease of coagulation disorder and it is a recessive disorder linked to X-chromosome. The molecular study is conducted by indirect studies due to it is caused by heterogeneous mutations in gen of FVIII and FIX in 40 families with hemophilia A (HA) and 10 with hemophilia B (HB). DNA extraction was carried out by saline precipitation method in 293 blood samples and 19 samples of amniotic fluid, as well as the analysis of St14, Bcl I and Hind III polymorphism for the AH and Taq I, Xmn I and Dde I for BH. The PCR technique was used. In the caser of AH it was possible to achieve a 35 percent of information for St14 and Hind III and a 32.5 percent for Bcl. Dde polymorphism supplied more information for BH for a 33 percent; whereas the Taq I represented the 10 percent of information and Xmn I the 0 percent. We verified that from the families analyzed with HA, in 23 of them we there was information. Besides, in 4 families affected by HB there was information. A total of 19 prenatal diagnoses were made with a previous determination of fetus sex, including 3 males ill

Utilization of different methodologies for the characterization of Hb Hasharon heterozygotes

Hb Hasharon has an electrophoretic mobility similar to that of Hb S in cellulose acetate and a mobility between Hb S and C at acid pH. In high-performance liquid chromatography, Hb Hasharon shows a distinct chromatographic profile and retention time. The origin of this variant is a mutation in codon 47 (GAC --> CAC) of the alpha2-globin gene, resulting in the replacement of asparagine by histidine during the translation process. Ten blood samples from individuals suspected of being Hb Hasharon carriers were analyzed. In addition to classic laboratory tests and high-performance liquid chromatography, molecular analysis by polymerase chain reaction with restriction fragment length polymorphism designed in the laboratory was performed to confirm this mutation. The study of these cases showed that a combination of classical and molecular methodologies is necessary in the diagnosis of hemoglobinopathies for a correct hemoglobin mutant identification. The accurate identification of hemoglobin variants is essential for genetic counseling and choice of therapy.

A combination of five short tandem repeats of chromosome 15 significantly improves the identification of Prader-Willi syndrome etiology in the Argentinean population

Prader-Willi syndrome (PWS) is a multisystemic disorder caused by the loss of expression of paternally transcribed genes in the PWS critical region of chromosome 15. Various molecular mechanisms are known to lead to PWS: deletion 15q11-q13 (75% of cases), maternal uniparental disomy (matUPD15) (23%) and imprinting defects (2%). FISH and microsatellite analysis are required to establish the molecular etiology, which is essential for appropriate genetic counseling and care management. We characterized an Argentinean population, using five microsatellite markers (D15S1035, D15S11, D15S113, GABRB3, D15S211) chosen to develop an appropriate cost-effective method to establish the parental origin of chromosome 15 in nondeleted PWS patients. The range of heterozygosity for these five microsatellites was 0.59 to 0.94. The average heterozygosity obtained for joint loci was 0.81. The parental origin of chromosome 15 was established by microsatellite analysis in 19 of 21 non-deleted PWS children. We also examined the origin of the matUPD15; as expected, most of disomies were due to a maternal meiosis I error. The molecular characterization of this set of five microsatellites with high heterozygosity and polymorphism information content improves the diagnostic algorithm of Argentinean PWS children, contributing significantly to adequate genetic counseling of such families.

Simulation of normal, carrier and affected controls for large-scale genotyping of cattle for factor XI deficiency

An insertion mutation within exon 12 of the factor XI gene has been described in Holstein cattle. This has opened the prospect for large-scale screening of cattle using the polymerase chain reaction (PCR) technique for the rapid identification of heterozygous animals. To facilitate such a screening process, the mutant and normal alleles of factor XI gene, represented by 244- and 320-bp PCR amplified fragments, were individually cloned in Escherichia coli using a multicopy plasmid cloning vehicle to generate pFXI-N and pFXI-M, respectively. The authenticity of the inserts was confirmed by nucleotide sequencing. A nested PCR method was developed, by which PCR amplicons generated from primers with annealing sites on the recombinant plasmids and by flanking the insert were used as templates for amplification of the diagnostic products using factor XI gene-specific primers. An equimolar mixture of both PCR amplicons, originating from pFXI-N and pFXI-M, constituted the carrier control while the individual amplicons were the affected and normal controls. The controls were used as references for in-gel comparison to screen a population of 307 cattle and 259 water buffaloes; the frequency of the mutant allele was found to be 0. No DNA size standards were required in this study. The simulated control DNA samples representing normal, carrier and affected cattle have the potential to help in large-scale screening of a cattle population for individuals that are carriers or affected by factor XI deficiency.

Use of methylation sensitive polymerase chain reaction for detection of fragile X full mutation & carrier state in males.

BACKGROUND & OBJECTIVE: Fragile X syndrome is the most common cause of inherited mental retardation. It is characterized by the progressive expansion of polymorphic (CGG) trinucleotide repeats located in the promoter region of the FMRI gene located at Xq27.3. The typical dysmorphic features that help in diagnosis are very often subtle or absent especially in pre-pubertal children. Confirmation is by molecular diagnosis based on repeat size and methylation analysis of the FMR1 gene. The present study was done to evaluate the utility of a methylation sensitive polymerase chain reaction (ms-PCR) method in the molecular diagnosis of fragile X syndrome in a select group of mentally retarded male children. METHODS: We used a methylation sensitive PCR technique, which initially modified DNA by bisulphite treatment. Two sets of PCR primers one each for methylated and unmethylated DNA sequences, were used. In full mutations, PCR specific for the methylated sequences was designed to amplify the CpG dinucleotide region upstream to the CGG repeats in clinically affected males. In healthy males and carriers, the second set of primers would amplify the unmethylated DNA sequences. The amplified PCR product size would help to differentiate between normal and premutation repeat size. RESULTS: In all, 25 blood samples collected from mentally retarded male children and five from normal controls were tested. Analysis of cases revealed one full blown mutation and one carrier state. These were further confirmed by southern blotting. INTERPRETATION & CONCLUSION: Unlike currently used methods, methylation sensitive PCR is a quick and accurate technique which could be used for the rapid screening of fragile X syndrome in mental retardation.

Quantitative Analysis of SMN1 Gene and Estimation of SMN1 Deletion Carrier Frequency in Korean Population based on Real-Time PCR

Spinal muscular atrophy (SMA) is an autosomal recessive disorder, caused by homozygous absence of the survival motor neuron gene (SMN1) in approximately 94% of patients. Since most carriers have only one SMN1 gene copy, several SMN1 quantitative analyses have been used for the SMA carrier detection. We developed a reliable quantitative real-time PCR with SYBR Green I dye and studied 13 patients with SMA and their 24 parents, as well as 326 healthy normal individuals. The copy number of the SMN1 gene was determined by the comparative threshold cycle (Ct) method and albumin was used as a reference gene. The homozygous SMN1 deletion ratio of patients was 0.00 and the hemizygous SMN1 deletion ratio of parents ranged from 0.39 to 0.59. The delta delta Ct ratios of 7 persons among 326 normal individuals were within the carrier range, 0.41-0.57. According to these data, we estimated the carrier and disease prevalence of SMA at 1/47 and 1/8,496 in Korean population, respectively. These data indicated that there would be no much difference in disease prevalence of SMA compared with western countries. Since the prevalence of SMA is higher than other autosomal recessive disorders, the carrier detection method using real-time PCR could be a useful tool for genetic counseling.

The validation of an automated liquid chromatography system for the diagnosis of thalassemias and hemoglobinopathies.

Accurate and precise hemoglobin separation and the quantitation of Hb A2 and Hb F are essential for the diagnosis of the thalassemias and hemoglobinopathies. Presented in this study is the validation of the the Hb A2 assay of the HbGold analyzer, a fully automated liquid chromatography system for hemoglobin separation and quantitation. Variability of Hb A2 quantitation was quite low; the CV's of within-run, between-run and interlaboratory studies were 1.8-3.1%, 3.4-6.0% and 6.8-8.8% respectively. The results of the %Hb A2 quantitated by HbGold analyzer correlated well with those given by the Bio-Rad Variant Hb testing system (r=0.98). The application of the HbGold analyzer for the diagnosis of the thalassemia phenotypes frequently observed in Thailand is considered. In conclusion, the Hb A2 assay of the HbGold analyzer could be used for the quantitation of Hb A2 and Hb F and the presumptive identification of abnormal hemoglobins.

Rapid carrier screening using short tandem repeats in the phenylalanine hydroxylase gene

Phenylketonuria [PKU] is an autosomal recessive genetic disorder caused by defects in the phenylalanine hydroxylase [PAH] system. Our work aimed to screen the PAH locus for the presence of potentially useful short tandem repeats [STR] as markers for carrier detection in PKU families in Egypt, and to determine the level of PAH heterozygosity within the Egyptian population. The system contains at least eight independent alleles in the Egyptian population, transmitted in a Mendelian fashion. Variations in the number of STR in the 16 families studied gave rise to polymorphisms that proved to be suitable markers for PKU carrier detection and prenatal diagnosis. The most frequent allelic fragment size in PKU patients was 246 bp [35.7%], which together with a fragment of 254 bp accounted for 60.7% of the mutant chromosomes

Thalassaemia control in developing countries--the Sri Lankan perspective.

Beta thalassaemia is a Mendelian recessive disorder. The economic and social cost of the disease is high due to patients' life long need for monthly blood transfusions and treatment with desferrioxamine, an iron chelating agent. Wider availability of cheaper drugs is on the horizon. If there is no concomitant reduction in the number of new thalassaemia major births, there will be a cumulative increase in numbers requiring treatment. The frequency and severity, and the economic and social costs of thalassaemia, support the case for the introduction of a carrier screening and counselling program in Sri Lanka. A three-pronged plan emphasising professional, political and public education in outlined.

A simple screening test for the detection of heterozygous beta thalassemia.

Beta-Thalassemia is prevalent in a high frequency of 5-15% in selected geographical areas and ethnic communities. There is need to screen large populations for the heterozygotes of beta-Thalassemia. We have evaluated NESTROFT (Naked eye single tube red cell osmotic fragility test) with 0.36% buffered saline in this study. Of the population screened, 42 cases were positive with NESTROFT, of which 40 were positive with the confirmatory test for beta-Thalassemia. This implies a positive predictive value and specificity of 100%, negative predictive value of 83.3% and sensitivity of 95.2%.

Prenatal diagnosis of haemophilia: a preliminary report.

BACKGROUND: Haemophilia A is the most common congenital bleeding disorder seen in man, affecting one in 5000 to 10,000 males. Because of the large size and heterogeneity of mutations in the factor VIII gene, direct detection of mutations is not practically feasible, except the recently detected intron 22 inversions. Hence, the indirect method of gene tracking using various polymorphic markers is the method of choice. Using this approach, we have performed antenatal diagnosis in four haemophilia A families. METHODS: The four families included 21 subjects who were used for gene-tracking analysis. Two families had a positive history with more than one member affected, while the remaining two families had a negative history with only one affected son. In all four families, the propositi and their affected relatives had severe haemophilia A with factor VIII:C less than 1%. All were negative for inhibitors. The polymorphic markers used were IVS 18 Bcl I, IVS 19 Hind III and the extragenic DXS 52 St 14 of the factor VIII gene. Prior to polymorphism analysis, the sex of the foetus was determined using Y chromosome-specific primers. All the analyses were carried out by polymerase chain reaction. RESULTS: Antenatal diagnosis in the four families showed three normal male foetuses and one normal female foetus. Two families provided evidence with only IVS 18 Bcl I and St 14 markers. One family provided information with only intron 19 Hind III marker. The fourth family provided information with all three markers. The coagulation parameters were almost in agreement with the results of DNA analysis. CONCLUSION: All three polymorphic markers yielded information. This suggests that these three markers can be effectively used in the antenatal diagnosis of haemophilia A in Indian families.

Análisis bioquímico y molecular de pacientes con ictiosis ligada al X y detección de portadoras / Biochemical and molecular analysis of patients and carriers of X-linked ichthyosis

La ictiosis ligada al X es una genodermatosis causada por la deficiencia de la sulfatasa esteroidea. Tiene una frecuencia de 1 por 2,000-6,000 recién nacidos vivos masculinos. Se inicia al nacimiento y se caracteriza por presentar escamas oscuras, adherentes, regulares con predominio en tronco y estremidades. El diagnóstico diferencial se realiza con la ictiosis vulgar, que tienen una frecuencia de 1 por 250 recién nacidos vivos. La determinación de la sulfatasa esteroidea clasifica a pacientes y portadoras con ictiosis ligada al X. El objetivo del presente trabajo fue establecer el diagnóstico correcto de pacientes y detección de portadoras en 10 familias con ictiosis ligada al X, amplificando mediante reacción en cadena de la polimerasa los extremos 5' y 3' del gen de la sulfatasa esteroidea y determinando la actividad de esta enzima en leucocitos utilizando el sulfato de 7-[3H]-dehidroepiandrosterona como substrato. Ningún paciente amplificó los extremos 5' y 3' del gen de la sulfatasa esteroidea, indicando la pérdida del gen en todos los casos. La determinación de la actividad de la sulfatasa esteroidea clasificó adecuadamente a pacientes (0.0 pmol/mg proteína/h) y portadoras (0.20 ñ 0.06 pmol/mg proteína/h versus 0.84 ñ 0.10 de controles sanos y pacientes con ictiosis vulgar) de ictiosis ligada al X. De esta manera, se establece la necesidad de realizar el ensayo de la sulfatasa esteroidea para el diagnóstico correcto de ictiosis ligada al X y para diferenciarla de la ictiosis vulgar e identificar a posibles portadoras de ictiosis ligada al X

La nueva genética / The new genetics

Actualmente, la genética moderna se considera una disciplina central en el estudio de la variabilidad y la herencia humana; ha permitido el entendimiento de muchas enfermedades de las diferentes áreas médicas y en un futuro se esperan importantes logros. El modelo de herencia mendeliana en la que rasgos dominantes y recesivos se transmiten de acuerdo a la segregación cromosómica es la base del conocimiento de las enfermedades genéticas. Sin embargo, muchos clínicos se encuentran con familias cuya historia genética no se explica fácilmente por este esquema. La genética molecular ha revelado nuevos mecanismos acerca de la herencia humana que permite explicar esta ®herencia no tradicional¼, la cual incluye principalmente: el mosaicismo, herencia mitocondrial, impronta genómica, disomía uniparental y enfermedades por trinucleótidos de repetición