Caracterización citogenética en cáncer laríngeo / Cytogenetic characterization in laryngeal cancer

El cáncer laríngeo representa un 23 por ciento de las neoplasias malignas en la práctica clínica del otorrinolaringólogo. Mediante técnicas de citogenética se ha logrado describior cambios en el DNA de tumores epiteliales de cabeza y cuello, siendo lo mas frecuentes pérdida de 3p, 8p y 18q. Entre Mayo de 1996 y Julio de 1997 se estudiaron 13 pacientes con diagnóstico de cáncer laríngeo. Las alteraciones encontrada corresponden a pérdida del cromosoma Y, alteraciones del cromosoma 5, 4q+, 2p-y manosomía del cromosoma 15

[Clinical and molecular screening for fragile X syndrome in 300 patients with non-specific mental retardation]. / Pesquisa molecular y clínica del síndrome de X-frágil en 300 pacientes con retardo mental inespecífico.

BACKGROUND: Fragile X syndrome is the most frequent cause of mental retardation linked to the X chromosome. In the majority of cases, the mutation responsible for the syndrome is an expansion of the trinucleotide repeat (CGG)n, present in the 5' region of exon 1 of the gene for mental retardation associated with fragile X syndrome (FMR-1). AIM: To report the results of a fragile X screening in patients with mental retardation. PATIENTS AND METHODS: Fragile X screening using polymerase chain reaction methods was done in 386 X chromosomes from 300 patients (214 male), aged 4 to 26 years old. The modified Hagerman test was applied to male patients. Hybridization techniques were applied in a subgroup of 51 patients. RESULTS: (CGG)n 30 was the allele found with the highest frequency in 50.2% of patients. (CGG)n 29 was found in 29% of patients. One subject had an allele with 46 CGG repeats, which corresponds to the gray zone. Hybridization studies were highly concordant with PCR, detecting four males with fragile X syndrome and a carrier female. The average clinical score of mental retardation not due to fragile X syndrome was 10.3 +/- 3.4 (range 3 to 23), and 97% of males had a score below 19. The concordance between scores over 20 and molecular genotype was 98%. CONCLUSIONS: The distribution of (CGG)n repeats, observed in this study, was significantly different to that previously reported for a normal Chilean population. The dispersion of molecular status and clinical score was lower than previously described using cytogenetic techniques.

Distribution of (CGG)n and FMR-1 associated microsatellite alleles in a normal Chilean population.

We report on the allele distribution in a normal Chilean population at 2 microsatellite loci neighbouring the FRAXA locus and at the CGG repeat in the 5' end of the FMR-1 gene, which causes the fragile X syndrome. The most common CGG repeat allele was 30 (41.7%), with 29 being second most common (30.2%). This distribution was similar from that seen in Caucasians but different from that observed in Chinese controls, where the most common allele was 29 repeats. Four alleles of FRAXAC1 and 6 of DXS548 were observed in the Chilean sample. A striking linkage disequilibrium of FMR-1 alleles with FRAXAC1 alleles was observed. In 90% of the 30 CGG repeat alleles only 31% of the 29 CGG repeat alleles had the FRAXAC1 154 bp allele. This result is in agreement with the suggestion that slippage between CGG repeat alleles 29 and 30 and between 152 and 154 FRAXAC1 alleles is very rare. This study suggests a founder chromosome effect in the Chilean population.

[Fragile X syndrome. Clinical analysis of 300 Chilean patients with unspecific mental retardation]. / Síndrome de X frágil. Análisis clínico en 300 pacientes con retardo mental inespecífico en la población Chilena.

BACKGROUND: Fragile X syndrome is the most important cause of sex linked mental retardation and the second of chromosomal origin, after Down syndrome. AIM: To apply the modified Hagerman score to patients with mental retardation and to relate clinical findings with cytogenetic and molecular diagnosis. PATIENTS AND METHODS: The modified Hagerman score was applied to 214 male and 86 female patients with mental retardation. The clinical variables in non fragile X and fragile X cases, determined by molecular and cytogenetic methods, were compared. RESULTS: The score in 210 non fragile X males was 10.5 + 3.7 (range 3-23), compared to 21.4 + 2.1 (range 19 to 23) in the four fragile X patients. All fragile X patients had mental retardation, attention deficits, hyperactivity disorders, hand biting and poor visual contact. Hand biting, flapping and perserving speech were observed in a significantly higher number of fragile X males. Only one of 86 females had fragile X syndrome: Her most relevant findings were a long face and high forehead, an attention deficit, hyperactivity and poor visual contact. No clinical differences with other mentally retarded females were found. CONCLUSIONS: Approximately 5% of institutionalized males with mental retardation have a fragile X syndrome.

[Molecular and genetic features of fragile X syndrome]. / Aspectos genético moleculares del síndrome de X-frágil.

The fragile-X syndrome is the most frequent cause of sexlinked mental retardation. In the majority of the cases the mutation responsible for the Martin Bell syndrome is produced when an expansion of the (CGG)n repetition is present in the region 5' of the exón 1 of the gene for X-fragile mental retardation 1 (FMR1), together with a hipermethylation in the CpG promoter region of the gene. The result of this situation is the absence of FMRP protein coded by the gene. The correlation between length of the (CGG)n sequences and of the X-fragile phenotype has permitted a more precise diagnosis of affected and carrier individuals by means of direct DNA analysis. Nevertheless the molecular genetic basis of the instability and expansion of the (CGG)n sequence represents a problem not yet resolved. Two polymorphic microsatellite (AC)n repetitions, FRAXAC1 and FRAXAC2 that flank the FMR-1 gene have been recently described. It has been suggested that some haplotypes of FRAXAC1 and FRAXAC2 could be associated to long (CGG)n repetitions and that these haplotypes would confer more instability to the repeated fragment thus increasing the probability of expansion. It has also been described that the (CGG)n repetition of the FMR-1 gene is interrupted by AGG trinucleotides and that the loss of one AGG would be an important mutational event in the generation of predisposing unstable alleles of of the X-fragile syndrome.

CFTR mutations in Chilean cystic fibrosis patients.

An analysis of five of the most common cystic fibrosis (CF) mutations worldwide (delta F-508, R-553X, G-551D, N-1303K and G-542X) was performed in 36 Chilean patients. Polymerase chain reaction (PCR) amplification of the DNA followed by allele specific restriction enzyme analysis was used for detection. The overall frequencies of the mutations in the chromosomes analyzed were 29.2% for delta F-508 and 4.2% for R-553X (n = 72). The G-542X, G-551D and N-1303 K mutations were absent in the Chilean sample. Our data suggest however that delta F-508 is not the most common CF mutation in Chilean patients. delta F-508 and R-553X account for only 33.4% of the alleles; 66.6% of them do not respond to the probes used and still remain uncharacterized.

[Amniotic band syndrome: description of 2 clinical cases and discussion on etiopathogenesis]. / Síndrome de bridas amnióticas: descripción de dos casos clínicos y discusión etiopatogénica.

The paper reports two cases in which infants were born with alterations described as the Amniotic Band Syndrome. The first one shows inferior limbs in bizarre positions, and the superior mutilated; also a cleft lip was present. The second case corresponds to a newborn with a facionucal band that almost separates the mouth from the rest of the face. Pathogenic theories are reexamined in face of the cases presented.

[Molecular genetic study of cystic fibrosis in the Chilean population. Relationship to its clinical expression]. / Estudio genético molecular de la fibrosis quística en la población Chilena. Relación con su expresión clínica.

Aiming to establish a genotype-phenotype relationship and to search a clinical expression in heterozygotes, 25 Chilean subjects with Cystic Fibrosis and 165 relatives were subjected to a clinical-molecular study. The most common mutations found worldwide were studied: delta F-508, G-542X, N-1303K, R-553X and G551D. Clinical and laboratory assessment comprised chest X-rays, spirometry, clinical evaluation, nutritional assessment, sweat test and carotenemia. Age at diagnosis was lower among homozygotes for the mutation delta F-508. In this group, Brasfield and Schawchman scores were better, probably due to an earlier initiation of treatment. No other differences were found among genotypic groups or relatives. Genetic markers indicated a higher european component of the sample, compared to the general Chilean population.

[Frequency and characteristics of genetic morbidity in a pediatric hospital]. / Frecuencia y características de la morbilidad genética en un hospital pediátrico.

Frequency and characteristics of patients discharged with recognized genetic diseases by current technical literature available in 1988 (GD) from a pediatric hospital at Santiago, Chile, are described. On the last three months of year 1988, a prospective study on 2,987 hospital admissions corresponding to 1,196 patients was done. Prevalence and incidence of GD were 62.5% and 17% among hospital admissions as a whole and 49.75% and 47.7% respectively when only individual patients were considered. No sex differences were found between patients with and without GD, but the frequency of GD was significantly higher in patients staying 7 or more weeks in hospital (12% vs. 3.4%), as among those who required two or more admissions (10.9% vs. 4.3%) or were referred from outside metropolitan Santiago (37.3% vs. 5.1%). First ten more frequent GD, in decreasing order of importance, were cardiac malformations, leukemias, cleft lip and/or palate, congenital dislocation of the hip, epilepsy and convulsions, idiopathic scoliosis, Down's syndrome, anal malformations, aganglionic megacolon and cystic fibrosis. The importance of diseases with genetic background is thus emphasized in a pediatric hospital.