Orbital metastasis: Clinical presentation and survival in a series of 11 cases.

BACKGROUND AND OBJECTIVE: Orbital metastases are an uncommon condition. They may be the clinical presentation of a previously unknown malignancy. Depending on the series, the rate of orbital metastasis as a first manifestation of a malignant tumour is 20%-42%. The clinical presentation and survival is presented in a series of 11 cases of orbital metastasis corresponding to 10 patients. MATERIAL AND METHODS: Descriptive retrospective study of a series of 10 adult patients diagnosed with orbital metastasis from solid tumours during a 9-year period. Metastasis involving the orbit was included, and lymphomas and contiguity invasions from adjacent structures were excluded. A note was made on whether the clinical picture was the first sign of tumour onset. Signs and symptoms at clinical debut were registered, as were primary tumour location, distance seeding, orbital structures involved, and survival time since the diagnosis was established. RESULTS: One-half (50%) of the patients were women. Mean age at diagnosis was 60.9 years (range 42-82). In nine cases (90%), the metastasis was unilateral, while in the remaining one the involvement was bilateral. The most frequent primary tumour location was the breast (36% of the cases); followed by the bladder (27%), lung (18%), and ovary and cavum (9%). Seventy percent of the patients had a previously diagnosed neoplasm; in 3 cases the metastasis was the first malignancy manifestation. Most frequent symptoms were diplopia (60%), visual impairment (40%), and pain (30%). The most common signs were resistance to ocular retropulsion (60%), presence of a mass on orbital palpation, and ocular dystopia (50%), and bulbar hyperaemia and proptosis (40%). The most employed management modality was clinical observation (5 patients). In 3 patients radiotherapy was administered, combining chemotherapy plus hormonal therapy in one case, and orbital exenteration in another one. In 2 cases, chemotherapy was administered as an isolated regime. Median survival time was 4.8 months since the diagnosis. There was a statistically significant difference between the survival time in the observation group (median 2.5 months) and in the active treatment group (median 29.2 months), p=.034. CONCLUSIONS: In the series presented, 27% of the cases established the clinical debut of the malignant neoplasm. The ophthalmologist plays an essential role when this condition is suspected, diagnosing it, and proposing its management together with the Oncology Service.

Metástasis orbitarias: presentación clínica y supervivencia en una serie de 11 casos / Orbital metastasis: Clinical presentation and survival in a series of 11 cases

Antecedentes y objetivoLas metástasis orbitarias son una entidad infrecuente y pueden suponer la presentación de un tumor maligno desconocido previamente; según las series, el porcentaje de metástasis orbitarias como primera manifestación de una enfermedad maligna es del 20-42%. Describimos la presentación clínica y la supervivencia en una serie de 11 casos de metástasis orbitarias correspondientes a 10 pacientes.Material y métodosEstudio descriptivo retrospectivo de una serie de 10 pacientes adultos diagnosticados de metástasis orbitarias de tumores sólidos durante un periodo de 9años. Se incluyeron metástasis que afectasen a la órbita, excluyendo linfomas e invasiones por contigüidad. Se especificó si la clínica fue la primera manifestación del tumor. Se registraron los síntomas y signos en el debut clínico, la localización del tumor primario, si existía extensión a distancia, las estructuras orbitarias afectas y el tiempo de supervivencia desde el diagnóstico.ResultadosLa mitad de los pacientes fueron mujeres. La edad media al diagnóstico fue de 60,9años (rango 42-82). En 9casos (90%) la metástasis fue unilateral, mientras que en el restante la afectación fue bilateral. La localización más frecuente del tumor primario fue la mama (36% de los casos), seguida por la vejiga (27%), el pulmón (18%), el ovario y el cavum (9%). El 70% de los pacientes tenían enfermedad neoplásica diagnosticada previamente; en 3casos la metástasis fue la primera manifestación del tumor.

Background and objectiveOrbital metastases are an uncommon condition. They may be the clinical presentation of a previously unknown malignancy. Depending on the series, the rate of orbital metastasis as a first manifestation of a malignant tumour is 20-42%. The clinical presentation and survival are presented in a series of 11 cases of orbital metastasis corresponding to 10 patients.Material and methodsDescriptive retrospective study of a series of 10 adult patients diagnosed with orbital metastasis from solid tumours during a 9-year period. Metastases involving the orbit were included, and lymphomas and contiguity invasions from adjacent structures were excluded. A note was made on whether the clinical picture was the first sign of tumour onset. Signs and symptoms at clinical debut were registered, as were primary tumour location, distance seeding, orbital structures involved, and survival time since the diagnosis was established.ResultsOne-half (50%) of the patients were women. Mean age at diagnosis was 60.9years (range 42-82). In nine cases (90%), the metastasis was unilateral, while in the remaining one the involvement was bilateral. The most frequent primary tumour location was the breast (36% of the cases), followed by the bladder (27%), lung (18%), and ovary and cavum (9%). Seventy percent of the patients had a previously diagnosed neoplasm; in 3 cases the metastasis was the first malignancy manifestation. Most frequent symptoms were diplopia (60%), visual impairment (40%), and pain (30%).

Orbital metastasis: Clinical presentation and survival in a series of 11 cases. / Metástasis orbitarias: presentación clínica y supervivencia en una serie de 11 casos.

BACKGROUND AND OBJECTIVE: Orbital metastases are an uncommon condition. They may be the clinical presentation of a previously unknown malignancy. Depending on the series, the rate of orbital metastasis as a first manifestation of a malignant tumour is 20-42%. The clinical presentation and survival are presented in a series of 11 cases of orbital metastasis corresponding to 10 patients. MATERIAL AND METHODS: Descriptive retrospective study of a series of 10 adult patients diagnosed with orbital metastasis from solid tumours during a 9-year period. Metastases involving the orbit were included, and lymphomas and contiguity invasions from adjacent structures were excluded. A note was made on whether the clinical picture was the first sign of tumour onset. Signs and symptoms at clinical debut were registered, as were primary tumour location, distance seeding, orbital structures involved, and survival time since the diagnosis was established. RESULTS: One-half (50%) of the patients were women. Mean age at diagnosis was 60.9years (range 42-82). In nine cases (90%), the metastasis was unilateral, while in the remaining one the involvement was bilateral. The most frequent primary tumour location was the breast (36% of the cases), followed by the bladder (27%), lung (18%), and ovary and cavum (9%). Seventy percent of the patients had a previously diagnosed neoplasm; in 3 cases the metastasis was the first malignancy manifestation. Most frequent symptoms were diplopia (60%), visual impairment (40%), and pain (30%). The most common signs were resistance to ocular retropulsion (60%), presence of a mass on orbital palpation and ocular dystopia (50%), and bulbar hyperaemia and proptosis (40%). The most employed management modality was clinical observation (5 patients). In 3 patients radiotherapy was administered, combining chemotherapy plus hormonal therapy in one case, and orbital exenteration in another one. In 2 cases, chemotherapy was administered as an isolated regime. Median survival time was 4.8months since the diagnosis. There was a statistically significant difference between the survival time in the observation group (median 2.5months) and in the active treatment group (median 29.2months), P=.034. CONCLUSIONS: In the series presented, 27% of the cases established the clinical debut of the malignant neoplasm. The ophthalmologist plays an essential role when this condition is suspected, diagnosing it, and proposing its management together with the Oncology Service.

Es la prueba del lazo un buen predictor de complicaciones hemorrágicas en pacientes con dengue? / Is the test of the tie a good predictor of hemorragic complication in patients with dengue?

Introducción: El dengue es una enfermedad que puede cursar con complicaciones hemorragicas. La prueba del lazo es un método recomendado como criterio diagnóstico de Fiebre Hemorrágica Dengue. Objetivos: Describir las manifestaciones hemorrágicas más frecuentes, hallar la sensibilidad y especificidad de la prueba del lazo, en relación al recuento de plaquetas y a la presencia de manifestaciones hemorrágicas espontáneas. Metodología: diseño observacional descriptivo, retrospectivo, de corte transverso, con componentes analíticos. Población de estudio: se estudiaron 245 pacientes, 170 mujeres (69%) y 75 varones (31%), con cuadro clínico compatible con dengue, que consultaron entre diciembre 2006 abril 2007 en el Hospital Nacional. Muestreo: no probabilístico, de casos consecutivos. Resultados:Las manifestaciones hemorrágicas espontáneas más frecuentes fueron las petequias 18 casos (7,3 %) , gingivorrágias 14 casos (5,7%) y epistaxis 11 casos (4,5 %) La sensibilidad y especificidad de la prueba del lazo, en relación con el recuento de plaquetas , fue del 27,7% y 84,5%. La prueba del lazo, en relación a la presencia de manifestaciones hemorrágicas, presentó una sensibilidad del 30,7% y especificidad del 85,4%. Conclusiones: La prueba del lazo no fue un buen método predictor de aparición de manifestaciones hemorrágicas por su baja sensibilidad. Sin embargo, cunado está ausente, ungran porcentaje de los pacientes no presentaron manifestaciones hemorrágicas, lo que dió una alta espeficidad...

Structure and energetics of clustered damage sites.

Quantum calculations on duplex DNA trimers were used to model the changes in structure, hydrogen bonding, stacking properties, and electrostatic potential induced by oxidized purine bases and abasic (AP) sites. Results for oxidized purine bases were consistent with experimental data that show small structural and energetic perturbations induced by isolated 8-oxoguanine (8oG). Watson-Crick base pairing was preserved, and no major distortions of the backbone were induced. The thermal destabilization of DNA induced by 8oG was comparable to the energy of a single hydrogen bond. In contrast, AP sites caused substantial distortions of the DNA backbone that were accompanied by relocation of counterions. The loss of Watson-Crick hydrogen bonds in AP sites had the potential to destabilize DNA by 10-20 kcal/mol (0.4-0.8 eV); however, new inter- and intrastrand hydrogen bonds formed after removal of a nucleic acid base that significantly affected the energy of AP sites and introduced a strong dependence on sequence context. Quantum calculations on small DNA fragments provided starting conformations and force-field parameters for classical molecular dynamics simulations of radiation-induced single-strand breaks that most often combine hydrolysis of a phosphate-oxygen (P-O) bond with an AP site and fully or partially degraded sugar ring. P-O bond hydrolysis increased the freedom in backbone torsion angles, which allowed the broken strand to compress and partially fill the hole in the DNA created by the AP site. Results for strand breaks with a 3'phosphoglycolate were similar to those with phosphate end groups.

Images reproducibility of an electrical impedance tomography (EIT) prototype. Analysis of the EIT sensibility in rats in pathological in vivo conditions.

The development of a 16 electrode-electrical impedance tomography (EIT) prototype to be applied in neurological fields such as epilepsy in rats has been previously reported. Approaching residual problems in order to improve its performance, this work reports results about changes made in the system hardware as follows: 1) replacing the current source demultiplexing circuit that could impact on a better spatial localization, and 2) a new current source design that increases the current amplitude up to 5 mA/sub rms/. System was evaluated by means of: a) image reproducibility starting from 4 test elements in homogeneous conditions; and b) spatial localization evaluation in conductivity perturbation conditions; this feature is evaluated too in preliminary acute in vivo experiments where an epileptic seizure is induced, and an impedance increase is expected. Results show a 95% of proper images for a) analysis. Spatial localization reports improvement up to 20% transversely and 5.5% longitudinally with regard to previous results. In vivo results are lack of interpretation due poor changes obtained in images. In order to conclude or not a reliable correlation between the perturbation measured and the seizure activity, a new definition of grey scale or other changes could be proposed.

Characterization of benzodiazepine receptor binding in immature rat brain after kainic acid administration.

PURPOSE: To evaluate the effects of status epilepticus on benzodiazepine (BDZ) receptor binding in immature rat brain. METHODS: Twenty-four immature (15 days old) and six adult (90 days old) rats were used in this study. Status epilepticus was induced in immature animals by administration of kainic acid (7 mg/kg intraperitoneal), whereas adults rats received saline. Animals were killed 72 hours or 35 days after treatment, and their brains were used for in vitro autoradiography experiments to determine BDZ binding. RESULTS: In basal conditions and compared with the adult group, immature animals presented reduced BDZ binding in the entorhinal cortex, substantia nigra pars reticulata, and periaqueductal gray. Seventy-two hours after kainic acid-induced status epilepticus, immature rats showed significantly increased BDZ in the frontal (48%), cingulate (39%), sensorimotor (39%), piriform (57%), and entorhinal (59%) cortices, the medial (84%) and basolateral (27%) amygdaloid nuclei, the dentate gyrus (51%), and the substantia nigra pars reticulata (43%). Thirty-five days after status epilepticus, immature rats displayed decreased BDZ binding in the entorhinal cortex (48%), dentate gyrus (36%), and fields CA1, CA2, and CA3 of Ammon's horn (30%). CONCLUSIONS: The present study demonstrates that status epilepticus and temporal lobe epilepsy produce a characteristic pattern of BDZ binding changes in the immature rat brain that differs from the one previously seen in adults.

Mutations affecting mRNA splicing are the most common molecular defects in patients with neurofibromatosis type 1.

Neurofibromatosis type 1 (NF1) is one of the most common inherited disorders in humans and is caused by mutations in the NF1 gene. To date, the majority of the reported NF1 mutations are predicted to result in protein truncation, but very few studies have correlated the causative NF1 mutation with its effect at the mRNA level. We have applied a whole NF1 cDNA screening methodology to the study of 80 unrelated NF1 patients and have identified 44 different mutations, 32 being novel, in 52 of these patients. Mutations were detected in 87% of the familial cases, but in 51% of the sporadic ones. At least 15 of the 80 NF1 patients (19%) had recurrent mutations. The study shows that in 50% of the patients in whom the mutations were identified, these resulted in splicing alterations. Most of the splicing mutations did not involve the conserved AG/GT dinucleotides of the splice sites. One frameshift, two nonsense and two missense mutations were also responsible for alterations in mRNA splicing. The location and type of mutation within the NF1 gene, and its putative effect at the protein level, do not indicate any relationship to any specific clinical feature of NF1. The high proportion of aberrant spliced transcripts detected in NF1 patients stresses the importance of studying mutations at both the genomic and RNA level. It is possible that part of the clinical variability in NF1 could be due to mutations affecting mRNA splicing, which is the most common molecular defect in NF1.

Prenatal diagnosis of sporadic neurofibromatosis type 1 (NF1) by RNA and DNA analysis of a splicing mutation.

Neurofibromatosis type 1 (NF1) is one of the most common genetic disorders in humans with an incidence of 1 in 3500. Most of the NF1 mutations reported so far (over 240 mutations) are unique. Specific prenatal diagnosis can only be provided to familial cases by an indirect linkage analysis or to families with a previously identified mutation. Here we report the first prenatal diagnosis in sporadic NF1 by direct characterization of the mutation. We first identified the skipping of exon 10b of NF1 in the mRNA from a woman affected by NF1 and without familial history of the disease. The analysis of genomic DNA identified mutation IVS10b+1G-->A as the cause of the skipping of exon 10b. Chorionic villus sampling (CVS) was performed at 10 weeks of gestation and total RNA was directly extracted from the sample. After reverse transcription (RT) and polymerase chain reaction (PCR) of the cDNA, the skipping of exon 10b was not identified in the CVS upon agarose gel electrophoresis. The fetal origin of the CVS was confirmed via polymorphic markers and the absence of the IVS10b+1G-->A mutation was confirmed by genomic analysis.

A clinical variant of neurofibromatosis type 1: familial spinal neurofibromatosis with a frameshift mutation in the NF1 gene.

Spinal neurofibromatosis (SNF) has been considered to be an alternative form of neurofibromatosis in which spinal cord tumors are the main clinical characteristic. Familial SNF has been reported, elsewhere, in three families-two linked to markers within the gene for neurofibromatosis type 1 (NF1) and the other not linked to NF1-but no molecular alterations have been described in these families. We describe a three-generation family that includes five members affected by SNF. All the affected members presented multiple spinal neurofibromas and café au lait spots, one member had cutaneous neurofibromas, and some members had other signs of NF1. Genetic analysis, performed with markers within and flanking the NF1 gene, showed segregation with the NF1 locus. Mutation analysis, performed with the protein-truncation test and SSCP/heteroduplex analysis of the whole coding region of the NF1 gene, identified a frameshift mutation (8042insA) in exon 46, which should result in a truncated NF1 protein. The 8042insA mutation was detected in all five family members with the SNF/NF1 phenotype. To our knowledge, this is the first time that a mutation in the NF1 gene has been associated with SNF. The clinical homogeneity in the severity of the disease among the affected members of the family, which is unusual in NF1, suggests that a particular property of the NF1 mutation described here, a gene closely linked to NF1, or posttranscriptional events are involved in this severe neurological phenotype.

Confirmation of a double-hit model for the NF1 gene in benign neurofibromas.

Neurofibroma is a benign tumor that arises from small or large nerves. This neoplastic lesion is a common feature of neurofibromatosis type 1 (NF1), one of the most common autosomal dominant disorders. The NF1 gene codes for a protein called "neurofibromin." It possesses a region that shares a high homology with the family of GTPase-activating proteins, which are negative regulators of RAS function and thereby control cell growth and differentiation. The evidence points to the NF1 gene being a tumor-suppressor gene. NF1 patients also have an increased incidence of certain malignant tumors that are believed to follow the "two hit" hypothesis, with one allele constitutionally inactivated and the other somatically mutated. Recently, somatic loss of heterozygosity (LOH) has been described for neurofibromas, and mutations in both copies of the NF1 gene have been reported for a dermal neurofibroma. The aim of our study was the analysis of the NF1 locus in benign neurofibromas in NF1 patients. We performed LOH analysis on 60 neurofibromas belonging to 17 patients, 9 of them with family history of the disease and 8 of them sporadic. We have analyzed five intragenic NF1 markers and six extragenic markers, and we have found LOH in 25% of the neurofibromas (corresponding to 53% of the patients). In addition, we found that in the neurofibromas of patients from familial cases the deletions occurred in the allele that is not transmitted with the disease, indicating that both copies of the NF1 gene were inactivated in these tumors. Therefore, the recent reports mentioned above, together with our findings, strongly support the double inactivation of the NF1 gene in benign neurofibromas.

Sex differences in mutational rate and mutational mechanism in the NF1 gene in neurofibromatosis type 1 patients.

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder with a prevalence of around 1 in 3500, affecting all ethnic groups. The clinical manifestations of the disease are variable, even among members of the same family, and affect a variety of tissues and cell types, including skin, iris, central and peripheral nervous systems and skeletal system. It has been reported that the majority of sporadic mutations in NF1 arise in paternally inherited alleles. We present here a collaborative study of the parental origin and type of mutation in individuals with de novo NF1, who account for up to a half of all cases of clinically diagnosed NF1. We have studied intragenic and extragenic markers in 470 NF1 families. In 32 of these families it was possible to assess the parental origin of a de novo NF1 mutation either by linkage analysis (in families with three generations) or by the detection of an intragenic deletion in a sporadic NF1 case. Eleven of these 32 families have three generations (the second and third generation being affected), with the mutation (not a large deletion) being of paternal origin in 82% of them (P < 0.05). In the other 21 families an intragenic deletion was detected, in 76% being in the maternal chromosome and in 24% in the paternal one (P < 0.05). Our results suggest that in NF1 the majority of deletions occur in oogenesis, while other types of mutations should account for the paternally derived NF1 mutations.

Molecular characterization of the breakpoints of a 12-kb deletion in the NF1 gene in a family showing germ-line mosaicism.

Neurofibromatosis type 1 (NF1) is caused by deletions, insertions, translocations, and point mutations in the NF1 gene, which spans 350 kb on the long arm of human chromosome 17. Although several point mutations have been described, large molecular abnormalities have rarely been characterized in detail. We describe here the molecular breakpoints of a 12-kb deletion of the NF1 gene, which is responsible for the NF1 phenotype in a kindred with two children affected because of germline mosaicism in the unaffected father, who has the mutation in 10% of his spermatozoa. The mutation spans introns 31-39, removing 12,021 nt and inserting 30 bp, of which 19 bp are a direct repetition of a sequence located in intron 31, just 4 bp before the 5' breakpoint. The 5' and 3' breakpoints contain the sequence TATTTTA, which could be involved in the generation of the deletion. The most plausible explanation for the mechanism involved in the generation of this 12-kb deletion is homologous/nonhomologous recombination. Since sperm of the father does not contain the corresponding insertion of the 12-kb deleted sequence, this deletion could have occurred within the NF1 chromosome through loop formation. RNA from lymphocytes of one of the NF1 patients showed similar levels of the mutated and normal transcripts, suggesting that the NF1-mRNA from mutations causing frame shifts of the reading frame or stop codons in this gene is not degraded during its processing. The mutation was not detected in fresh lymphocytes from the unaffected father by PCR analysis, supporting the case for true germ-line mosaicism.

Two further cases of mutation R1947X in the NF1 gene: screening for a relatively common recurrent mutation.

We present two further cases of mutation R1947X in the neurofibromatosis type 1 gene. To date, a total of nine cases of mutation R1947X have been reported giving a frequency of about 2% and confirming the recurrence of this mutation. R1947X occurs within a CpG dinucleotide and supports the hypothesis that the mutation rate for this dinucleotide is higher than that of other dinucleotides. As routine analysis for R1947X is advisable, we have developed an allele-specific oligonucleotide hybridization assay for the efficient screening of a large number of samples.

[Electrolytic changes in children with acute lymphoblastic leukemia during remission induction]. / Alteraciones electrolíticas en niños con leucemia linfoblástica aguda durante la inducción de remisión.

The alterations of the water-electrolyte balance are among the commonest early complications of treatment in children with acute lymphoblastic leukaemia (ALL). A study was carried out in thirteen patients with ALL aged between 1.5 and 14 years. Four had high risk ALL and nine had standard risk ALL. All patients received intravenous epirubicin and vincristine, per os prednisone, allopurinol and bicarbonate, and intrathecal methotrexate and hydrocortisone. Venous blood was drawn before starting therapy and on days second and sixth of treatment in order to assay sodium, potassium, calcium, phosphate, magnesium, albumin, urea nitrogen, creatinine and uric acid concentrations. The following alterations were found: hyponatraemia in 4 cases, hypokalemia in 9, hypomagnesaemia in 9, hypocalcaemia in 11, hypophosphataemia in 9, hypouricemia in 3 and hyperuricaemia in 3 others. None of the patients developed acute renal insufficiency. These abnormalities could be due to the leukaemia itself or appear as a consequence of the remission induction treatment.

Prenatal diagnosis of neurofibromatosis type 1: from flanking RFLPs to intragenic microsatellite markers.

Even though the neurofibromatosis type 1 (NF1) gene was cloned more than 3 years ago, the process of identifying mutations has not been fruitful, and genetic counselling is mainly based on the use of linked markers. Since 1990, we have analysed 130 NF1 families and have performed six prenatal diagnoses. In each case, genetic counselling has relied on linked markers and informativity was achieved in all of them. The use of intragenic microsatellite polymorphisms (IVS27AAAT2.1, IVS27AC28.4, IVS27AC33.1, and IVS38GT53.0) has increased the informativeness in our series of NF1 families to an average of 90 per cent, providing accurate diagnosis and confirmation of the disease status.

Neurofibromatosis type 1 due to germ-line mosaicism in a clinically normal father.

BACKGROUND: The mutation rate of the neurofibromatosis type 1 (NF1) gene is one of the highest in the human genome, with about 50 percent of cases being due to new mutations. We describe a family in which neurofibromatosis type 1 occurred in two siblings with clinically normal parents, and we demonstrate germ-line mosaicism in the father. METHODS: We studied lymphocyte DNA from each member of the family and the father's spermatozoa for several polymorphic intragenic markers of the NF1 gene. Southern blots of DNA digested with several enzymes were hybridized with complementary DNA and individual NF1 exon probes to search for alterations in the gene. RESULTS: The affected siblings, with a clinically severe form of neurofibromatosis type 1, showed no inheritance of paternal alleles for a marker in intron 38 of the NF1 gene, whereas they received alleles from both parents for other NF1 markers. Analysis with probes from this region of the NF1 gene showed a 12-kb deletion of the NF1 gene, involving exons 32 to 39, in the affected offspring. Ten percent of the father's spermatozoa carried the same NF1 deletion, but the abnormality was not detected in DNA from his lymphocytes. CONCLUSIONS: The presence of the NF1 mutation in 10 percent of the clinically normal father's spermatozoa supports the hypothesis that most germ-line mutations occur in precursors of gametes. In cases of spontaneous mutation, analyzing the specific NF1 mutation in the father's sperm might help in the detection of mosaicism and thus facilitate genetic counseling about further pregnancies.

Two CA/GT repeat polymorphisms in intron 27 of the human neurofibromatosis (NF1) gene.

We describe two polymorphic microsatellites in intron 27 of the neurofibromatosis type 1 (NF1) gene. The microsatellites consist of TG/AC and AC/TG dinucleotide repeats detecting five and seven alleles and with heterozygosities of 0.46 and 0.72, respectively. These microsatellites are useful tools both for direct and indirect genetic analysis of NF1.

A highly informative CA/GT repeat polymorphism in intron 38 of the human neurofibromatosis type 1 (NF1) gene.

We describe a polymorphic microsatellite in intron 38 of the neurofibromatosis type 1 (NF1) gene. The microsatellite consists of a CA/GT dinucleotide repeat detecting 8 alleles; it has a heterozygosity of 82%.