Characterization of NF1 frameshift mutations in pediatric patients with neurofibromatosis type I.

Neurofibromatosis type I is an autosomal dominant disease with complete penetrance and variable age-dependent expressivity. It is caused by heterozygous mutations in neurofibromin 1 (NF1). These occur throughout the length of the gene, with no apparent hotspots. Even though some mutations have been found repeatedly, most have been observed only once. This, along with the variable expressivity, has made it difficult to establish genotype-phenotype correlations. Here, we report the clinical and molecular characteristics of four pediatric patients with neurofibromatosis type I. Patients were clinically examined and DNA was extracted from peripheral blood. The whole coding sequence of NF1, plus flanking intronic regions, was examined by Sanger sequencing, and four frameshift mutations were identified. The mutation c.3810_3820delCATGCAGACTC was observed in a familial case. This mutation occurred within a sequence comprising two 8-bp direct repeats (GCAGACTC) separated by a CAT trinucleotide, with the deletion leading to the loss of the trinucleotide and the 8-bp repeat following it. The deletion might have occurred due to misalignment of the direct repeats during cell division. In the mutation c.5194delG, the deleted G is nested between two separate mononucleotide tracts (AAAGTTT), which could have played a role in creating the deletion. The other two mutations reported here are c.4076_4077insG, and c.3193_3194insA. All four mutations create premature stop codons. In three mutations, the consequence is predicted to be loss of the GAP-related, Sec14 homology, and pleckstrin homology-like domains; while in the fourth, only the latter two domains would be lost.

Duplication of the Miller-Dieker Critical Region in a Patient with a Subtelomeric Unbalanced Translocation t(10;17)(p15.3;p13.3).

Submicroscopic duplications in the Miller-Dieker critical region have been recently described as new genomic disorders. To date, only a few cases have been reported with overlapping 17p13.3 duplications in this region. Also, small deletions that affect chromosome region 10p14→pter are rarely described in the literature. In this study, we describe, to our knowledge for the first time, a 5-year-old female patient with intellectual disability who has an unbalanced 10;17 translocation inherited from the father. The girl was diagnosed by subtelomeric FISH and array-CGH, showing a 4.43-Mb heterozygous deletion on chromosome 10p that involved 14 genes and a 3.22-Mb single-copy gain on chromosome 17p, which includes the critical region of the Miller-Dieker syndrome and 61 genes. The patient's karyotype was established as 46,XX.arr 10p15.3p15.1(138,206-4,574,436)x1,17p13.3(87,009-3,312,600)x3. Because our patient exhibits a combination of 2 imbalances, she has phenotypic features of both chromosome abnormalities, which have been reported separately. Interestingly, the majority of patients who carry the deletion 10p have visual and auditory deficiencies that are attributed to loss of the GATA3 gene. However, our patient also presents severe hearing and visual problems even though GATA3 is present, suggesting the involvement of different genes that affect the development of the visual and auditory systems.

Role of telomere length in subtelomeric gene expression and its possible relation to cellular senescence.

Transcriptional silencing of subtelomeric genes is associated with telomere length, which is correlated with age. Long and short telomeres in young and old people, respectively, coincide with gene repression and activation in each case. In addition, differential location of genes with respect to telomeres causes telomere position effect. There is very little evidence of the manner in which age-related telomere length affects the expression of specific human subtelomeric genes. We analyzed the relationship between telomere length and gene expression levels in fibroblasts derived from human donors at ages ranging from 0-70 years. We studied three groups of genes located between 100 and 150 kb, 200 and 250 kb, and > 300 kb away from telomeres. We found that the chromatin modifier-encoding genes Eu-HMTase1, ZMYND11, and RASA3 were overexpressed in adults. Our results suggest that short telomere length-related overexpression of chromatin modifiers could underlie transcriptional changes contributing to cellular senescence.

[Reliability of electrophysiological measurements of motor control]. / Fiabilidad de las medidas electrofisiológicas del control motor.

OBJECTIVES: The aim of the study was the short term test-retest-reliability of electrophyisiological correlates of simple processes of the motor control, i.e. the execution (go) and the inhibition (no go) of a prepared motor response, evoked during the Continuous Performance Test (CPT). Our interest was centered in the reliability of the topographical P300-parameters described in previous studies, i.e. the localizations of the go and no go centroids and the no go anteriorization (NGA), which is the difference between the two centroid locations. A sufficient reliability is a basic requirement for the application of these new topographical parameters for the investigation of different psychiatric illnesses with suspected dysfunctions of prefrontal motor control, e.g. schizophrenias and affective illnesses, obsessive-compulsive disorders, personality disorders with deficits in impulse control, and in children with attention deficit hyperactivity disorder. PATIENTS AND METHODS: We examined 23 healthy subjects who executed two versions of the CPT with an interval of 30 minutes. After averaging the obtained evoked potentials of each subject, we determined the latencies, amplitudes and positive centroids, at the moment of the peak of the Global Field Power in a P300 time window. RESULTS: Statistical analysis revealed sufficient test-retest-reliabilities in comparison to other electrophysiological paradigms, mainly for the localizations of the go (r = 0.93; p = 10(-10)) and no go centroid (r = 0.85; p = 10(-4)), as well as for the no go anteriorization (r = 0.63; p = 10(-3)). CONCLUSION: These results are a prerequisite for the application of these topographical parameters as measures of the prefrontal motor control in different healthy and psychiatric populations.

Ingestión y digestión de siete especies de microalgas por larvas de Strombus gigas (Mesogastropoda: Strombidae) / Ingestion and digestion of seven species of microalgae by larvae of Strombus gigas (Mesogastropoda: Strombidae)

The potential nutritional value of seven microalgal diets as measured by their ingestibility and digestibility to queen conch Strombus gigas larvae was tested with 30 day old larvae reared at 28 degrees C and fed at 1000 cells x ml(-1). The algae were Tetraselmis suecica, Tetraselmis chuii Isochrysis aff. galbana, Dunaliella tertiolecta, Chlamydomonas coccoides, Chaetoceros sp. and Thalassiosira fluviatilis. Ingestion and digestion were measured by the four nutritional stages studied with epifluorescence microscopy with live larvae. Temporal and absolute indices showed that larvae fed Chaetoceros sp. and T. fluviatilis had lower ingestion and digestion levels. The other algae are recommend to feed S. gigas larvae.

Ciclo reproductor e índices de condición usados en Melongena corona (Mollusca: Gastropoda) / Reproductive cycle and index of condition used for Melongena corona (Mollusca: Gastropoda)

Melongena corona bispinosa was studied in Yucatán, México (21 degrees 16' N, 89 degrees 49' W) for a year. Males have reproductive peaks in February and December, and a post-copulation peak in June. Female peaks are in March and May, plus oviposition peaks in April and January. Males and females differ in the mean gonadosom ic index (F=13.79, p<0.05) but not in the dry tissue/shell weight (F=0.0902, p<0.05), dry tissue and total weight (F=0.2466, p<0.05) and dry tissue weight/internal shell volume (F=1.0565, p<0.05).

Producción somática de dos especies de Crassostrea virginica e Ischadium recurvum (Bivalvia) en Mecoacán, Tabasco, México / Somatic production of two species: Crassostrea virginica and Ischadium recurvum Bivalvia in Mecoacán, Tabasco, México

The Mexican oyster fishery, 90% supported by the coastal lagoons of the Gulf of Mexico, has decreased drastically in the last six years as a result of anthropogenic pollution and improper management. The mussel Ischadium recurvum has proliferated and competes with oysters for space and probably food. Crassostrea virginica and Ischadium recurvum were studied to evaluate somatic production with biometry and physiological condition indices (PCI's) during an annual cycle. A random sample of 200 organisms was taken montly for each species. Condition indices wet flesh weigth: wet shell weight ratio (WFW/WSW), dry flesh weight: wet flesh weight ratio (DFW/WFW), dry flesh wet: dry shell weight ratio (DFW/DSW), and ash free dry weight: tissue dry weight (AFDW/TDW) were calculated. In order to stablish physiological condition and temporal variability, these indices were compared between species and months. The somatic production of mussels was higher than in oysters. This enhancement in production could be explained by: 1) Mussel uses less energy for shell production, 2) a constant recruitment of mussel almost year-round, and 3) the mesohalin lagoon was more favourable to the mussel.

Desarrollo embrionario de Strombus pugilis (Mesogastropoda: Strombidae) en el laboratorio / Embrionary development of Strombus pugilis (Mesogastropoda: Strombidae) in the laboratory

Stages from oviposition to veliger hatching are described for Strombus pugilis under laboratory conditions. Two egg masses from Playa Seyba, México, (20 degrees 45' N, 91 degrees 45' W) were used (three sub-samples per mass). Each sub-sample was immersed in a 11 container at 29 +/- 1 degrees C. This description is based on stages known from Strombus gigas, which include number of: fertilized eggs, morulae, gastrulae, trochophore larvae with slow movements, larvae with primordium foot, larvae with eyes, larvae with statocyst and veliger larvae. Eggs with first division appeared five hours after oviposition in the three replicates of each mass, although in greatest number in one of the egg masses. Trochophore larvae with slow movements appear after 50-54 hours and veligers hatch after 90 hours.

Distribución, abundancia, densidad y morfometría de Strombus gigas (Mesogasteropoda: Strombidae) en el Arrecife Alacranes, Yucatán, México / Distribution, abundance, density and morphometry of Strombus gigas (Mesogasteropoda: Strombidae) in Alacranes reef, Yucatán, México

A population of the conch Strombus gigas was sampled in 109 transects (100 x 10 m each) for an area of 109000 m2 (eight surveys in 1998 and six in 1999) in Yucatan, Mexico; S. gigas was the most abundant conch species (97% of individuals) and ocurred at depths of 0.5-18 m. Mean density was 0.0084 individuals/m2 (Standard deviation SD=0.0138, n=1910). Maximum density (0.015 individuals/m2) was at 0.5-2 m and minimal (0.001 individuals/m2) at 16-18 m. Shell length was 120-290 mm (mena=211.6, SD=26, n=1136). Shell lip thickness, measured only in adults, was 1-28 mm (mean=8.7, SD=7.5, n=1136).

Crecimiento y sobrevivencia de semillas del ostión Crassostrea virginica en una granja camaronícola en Yucatán, México / Growth and survival of seeds of the Crassostrea virginica oyster on a shrimp farm in Yucatán, México

A lot of 1600 seeds of American oyster Crassostrea virginica from the coastal lagoon La Redonda, Tabasco, Mexico was cultured in main drainage channel (S1), a secondary drainage channel (S2), the floodgate of a white shrimp Pennaeus vannamei pond (S3) and the marine water supply pond (S4). The seeds, with a total height and initial humid weight of 31.67 +/- 3.43 mm and 4.29 +/- 1.32 g, respectively, were cultured in suspended Nestier oyster boxes at 575 org/m2. Biological and environmental parameters were recorded after 296 days, the seeds in S4 reached height and weight values of 52.55 +/- 7.51 mm and 16.30 +/- 4.94 g, respectively. The index of physiologic condition along the experiment had a variation of 1.26% to 3.45%. In S4 the survival was 81.0%. In the other places the mortality was total after 90 days.

[Growth and survival of seeds of the oyster Crassostrea virginica in a shrimp farm in Yucatán, México]. / Crecimiento y sobrevivencia de semillas del ostión Crassostrea virginica en una granja camaronícola en Yucatán, México.

A lot of 1600 seeds of American oyster Crassostrea virginica from the coastal lagoon La Redonda, Tabasco, Mexico was cultured in main drainage channel (S1), a secondary drainage channel (S2), the floodgate of a white shrimp Pennaeus vannamei pond (S3) and the marine water supply pond (S4). The seeds, with a total height and initial humid weight of 31.67 +/- 3.43 mm and 4.29 +/- 1.32 g, respectively, were cultured in suspended Nestier oyster boxes at 575 org/m2. Biological and environmental parameters were recorded after 296 days, the seeds in S4 reached height and weight values of 52.55 +/- 7.51 mm and 16.30 +/- 4.94 g, respectively. The index of physiologic condition along the experiment had a variation of 1.26% to 3.45%. In S4 the survival was 81.0%. In the other places the mortality was total after 90 days.

[Distribution, abundance, density and morphometry of Strombus gigas (Mesogasteropoda: Strombidae) in Alacranes reef, Yucatán, México]. / Distribución, abundancia, densidad y morfometría de Strombus gigas (Mesogasteropoda: Strombidae) en el Arrecife Alacranes, Yucatán, México.

A population of the conch Strombus gigas was sampled in 109 transects (100 x 10 m each) for an area of 109000 m2 (eight surveys in 1998 and six in 1999) in Yucatan, Mexico; S. gigas was the most abundant conch species (97% of individuals) and ocurred at depths of 0.5-18 m. Mean density was 0.0084 individuals/m2 (Standard deviation SD=0.0138, n=1910). Maximum density (0.015 individuals/m2) was at 0.5-2 m and minimal (0.001 individuals/m2) at 16-18 m. Shell length was 120-290 mm (mena=211.6, SD=26, n=1136). Shell lip thickness, measured only in adults, was 1-28 mm (mean=8.7, SD=7.5, n=1136).

[Embrionary development of Strombus pugilis (Mesogastropoda: Strombidae) in the laboratory]. / Desarrollo embrionario de Strombus pugilis (Mesogastropoda: Strombidae) en el laboratorio.

Stages from oviposition to veliger hatching are described for Strombus pugilis under laboratory conditions. Two egg masses from Playa Seyba, México, (20 degrees 45' N, 91 degrees 45' W) were used (three sub-samples per mass). Each sub-sample was immersed in a 11 container at 29 +/- 1 degrees C. This description is based on stages known from Strombus gigas, which include number of: fertilized eggs, morulae, gastrulae, trochophore larvae with slow movements, larvae with primordium foot, larvae with eyes, larvae with statocyst and veliger larvae. Eggs with first division appeared five hours after oviposition in the three replicates of each mass, although in greatest number in one of the egg masses. Trochophore larvae with slow movements appear after 50-54 hours and veligers hatch after 90 hours.

[Somatic production of two species: Crassostrea virginica and Ischadium recurvum Bivalvia in Mecoacán, Tabasco, México]. / Producción somática de dos especies de Crassostrea virginica e Ischadium recurvum (Bivalvia) en Mecoacán, Tabasco, México.

The Mexican oyster fishery, 90% supported by the coastal lagoons of the Gulf of Mexico, has decreased drastically in the last six years as a result of anthropogenic pollution and improper management. The mussel Ischadium recurvum has proliferated and competes with oysters for space and probably food. Crassostrea virginica and Ischadium recurvum were studied to evaluate somatic production with biometry and physiological condition indices (PCI's) during an annual cycle. A random sample of 200 organisms was taken montly for each species. Condition indices wet flesh weigth: wet shell weight ratio (WFW/WSW), dry flesh weight: wet flesh weight ratio (DFW/WFW), dry flesh wet: dry shell weight ratio (DFW/DSW), and ash free dry weight: tissue dry weight (AFDW/TDW) were calculated. In order to stablish physiological condition and temporal variability, these indices were compared between species and months. The somatic production of mussels was higher than in oysters. This enhancement in production could be explained by: 1) Mussel uses less energy for shell production, 2) a constant recruitment of mussel almost year-round, and 3) the mesohalin lagoon was more favourable to the mussel.

[Reproductive cycle and index of condition used for Melongena corona (Mollusca: Gastropoda)]. / Ciclo reproductor e índices de condición usados en Melongena corona (Mollusca: Gastropoda).

Melongena corona bispinosa was studied in Yucatán, México (21 degrees 16' N, 89 degrees 49' W) for a year. Males have reproductive peaks in February and December, and a post-copulation peak in June. Female peaks are in March and May, plus oviposition peaks in April and January. Males and females differ in the mean gonadosom ic index (F=13.79, p<0.05) but not in the dry tissue/shell weight (F=0.0902, p<0.05), dry tissue and total weight (F=0.2466, p<0.05) and dry tissue weight/internal shell volume (F=1.0565, p<0.05).

[Ingestion and digestion of seven species of microalgae by larvae of Strombus gigas (Mesogastropoda: Strombidae)]. / Ingestión y digestión de siete especies de microalgas por larvas de Strombus gigas (Mesogastropoda: Strombidae).

The potential nutritional value of seven microalgal diets as measured by their ingestibility and digestibility to queen conch Strombus gigas larvae was tested with 30 day old larvae reared at 28 degrees C and fed at 1000 cells x ml(-1). The algae were Tetraselmis suecica, Tetraselmis chuii Isochrysis aff. galbana, Dunaliella tertiolecta, Chlamydomonas coccoides, Chaetoceros sp. and Thalassiosira fluviatilis. Ingestion and digestion were measured by the four nutritional stages studied with epifluorescence microscopy with live larvae. Temporal and absolute indices showed that larvae fed Chaetoceros sp. and T. fluviatilis had lower ingestion and digestion levels. The other algae are recommend to feed S. gigas larvae.

[Medical pathology due to trinucleotide repeats]. / Patología médica ocasionada por repetidos de trinucleótidos.

Trinucleotide repeat expansion is responsible for ten human diseases described so far. Four types of repeats are involved in these expansions, with type, number and position in the gene varying from one disease to another. In some fragile sites, the trinucleotide repeat is found to be enlarged to 200 or more. Smaller expansions have been found within coding regions of some genes that are associated with neurodegenerative diseases, such as Huntington's disease. The continuous expansion of the trinucleotide repeats in subsequent generations explains the genetic anticipation, peculiar to these disorders. Recently, it was shown that two expanded minisatellite sequences are also involved in both progressive myoclonus epilepsy type 1 and distamycin A-sensitive fragile site, FRA16B. This form of peculiar heredity is very important because of its relationship with some of the common human degenerative diseases.

Lambda prophage decreases Escherichia coli sensitivity to human serum bactericidal effect.

Escherichia coli C600 and C600(lambda) strains were tested for their susceptibility to the bactericidal action of 4% normal human serum. C600 survival was reduced to 30%, 23% and 16% after 60, 150 and 180 min of exposure to serum, respectively, whereas the percentage of survival of C600(lambda) was 199, 109 and 65% at the same times. The estimated exposition times for 50% killing showed an eight-fold difference, they were 23 and 202 min for C600 and C600(lambda), respectively. None of the two strains tested was killed when incubated with serum whose alternative complement pathway was inactivated by heating at 50 degrees C for 20 min, showing that this pathway, and not the classical one, was responsible of the bactericidal action, a conclusion further supported by the finding that both strains were differentially killed by the alternative complement pathway, C600 showing a 14X, 10X and 4X greater susceptibility than C600(lambda) at 60, 120 and 180 min of exposure to serum whose classical pathway was selectively inhibited by chelation with 10 mM EGTA plus 2 mM MgCl2. We feel that lambda phage may lower the serum sensitivity of its lysogen by altering the bacterial external surface, perhaps by the inclusion of some protein encoded by an accessory gene of the lambda genome, and thus interfering with either the formation, deposition or activity of the membrane attack complex.