LBDNet interlaboratory comparison for the dicentric chromosome assay by digitized image analysis applying weighted robust statistical methods.

PURPOSE: This interlaboratory comparison was conducted to evaluate the performance of the Latin-American Biodosimetry Network (LBDNet) in analyzing digitized images for scoring dicentric chromosomes from in vitro irradiated blood samples. The exercise also assessed the use of weighted robust algorithms to compensate the uneven expertise among the participating laboratories. METHODS: Three sets of coded images obtained through the dicentric chromosome assay from blood samples irradiated at 1.5 Gy (sample A) and 4 Gy (sample B), as well as a non-irradiated whole blood sample (sample C), were shared among LBDNet laboratories. The images were captured using the Metafer4 platform coupled with the AutoCapt module. The laboratories were requested to perform triage scoring, conventional scoring, and dose estimation. The dose estimation was carried out using either their laboratory calibration curve or a common calibration curve. A comparative statistical analysis was conducted using a weighted robust Hampel algorithm and z score to compensate for uneven expertise in dicentric analysis and dose assessment among all laboratories. RESULTS: Out of twelve laboratories, one had unsatisfactory estimated doses at 0 Gy, and two had unsatisfactory estimated doses at 1.5 Gy when using their own calibration curve and triage scoring mode. However, all doses were satisfactory at 4 Gy. Six laboratories had estimated doses within 95% uncertainty limits at 0 Gy, seven at 1.5 Gy, and four at 4 Gy. While the mean dose for sample C was significantly biased using robust algorithms, applying weights to compensate for the laboratory's analysis expertise reduced the bias by half. The bias from delivered doses was only notable for sample C. Using the common calibration curve for dose estimation reduced the standard deviation (s*) estimated by robust methods for all three samples. CONCLUSIONS: The results underscore the significance of performing interlaboratory comparison exercises that involve digitized and electronically transmitted images, even when analyzing non-irradiated samples. In situations where the participating laboratories possess different levels of proficiency, it may prove essential to employ weighted robust algorithms to achieve precise outcomes.

The BioDoseNet image repository used as a training tool for the dicentric assay.

Purpose: This paper describes how the BioDoseNet image repository was used as a training tool for the dicentric assay.Materials and methods: The training was implemented in three phases: introduction to dicentric scoring, dose response curve elaboration and dose assessment exercise. Four labs without previous experience in the dicentric assay participated and four modules of the repository were used.Results: The labs become familiar with aberrations induced by ionizing radiation. The labs were able to generate data for the elaboration of a dose response curve and then successfully estimated doses and irradiated fractions in six blind samples.Conclusions: The performance of these laboratories during the exercise demonstrates the efficacy of the BioDoseNet image repository as a training tool and the utility of web based scoring for the dicentric assay community.

45, X/46, XY variante de síndrome de turner reporte de un caso / 45,X/46,XY. avariation of turner syndrome. a case report

El síndrome de Turner es una anomalía cromosómica descrita por primera vez por el Dr. Henry Turner en 1938 que se manifiesta principalmente por talla baja, cuello ancho, pterigyumcolli, cubitus valgo e infantilismo sexual. Tiene una prevalencia de 1 en 1800 a 5000 recién nacidos vivos femeninos y se caracteriza por la ausencia total o parcial del segundo cromosoma X. Con las técnicas citogenéticas una gran variedad de presentaciones han sido reconocidas, siendo la más común la monosomía del cromosoma X (constitución cromosómica: 45,X) y los menos frecuentes los mosaicismos, entre los que se incluyen cromosomas marcadores que corresponderían a fragmentos o la totalidad de un cromosoma Y; la presencia de este cromosoma podría conferirle al paciente características fenotípicas masculinas. Se reporta el caso de una niña de 14 años de edad con fenotipo de síndrome de Turner que presentó una constitución cromosómica en mosaico 45,X/46,XY. Madre y padre de 32 años, no consanguíneos, la niña fue traída a la consulta por ausencia de vello axilar y pubiano, y ausencia de desarrollo mamario En el nacimiento la paciente presentó genitales ambiguos, labios abiertos, en bolsa derecha el testículo se presentó atrofiado y el izquierdo en pelvis, ambos fueron extirpados a los 3 y 6 meses de vida respectivamente. Se realiza una revisión de la literatura y se propone el asesoramiento genético adecuado a lo hallado en el cariotipo.

Turner syndrome (TS) is a chromosomal disorder discovered by Dr. Henry Turner in1938, is manifested clinically mainly by short stature, broad neck, pterigyumcolli, cubitusvalgus and sexual infantilism. It has a prevalence of 1 in 1800-5000 female live births andis characterized by the total or partial absence of the second X chromosome. A great varietyof presentations have been recognized due to cytogenetic techniques, the most commonbeing the monosomy of the X chromosome (chromosomal constitution: 45,X) and the lessfrequent mosaicism, including marker chromosomes that correspond to fragments or thewhole Y chromosome. The presence of this chromosome could confer male phenotypiccharacteristics to the patients. We report the case of a 14-year-old girl with a phenotypesimilar to Turner syndrome who presented a mosaic chromosomal constitution 45 X/46,XY.Both parents were 32-year old, nonconsanguineous; the child was brought to consultationfor absence of axillary and pubic hair and absence of breast development. At the birth thepatient presented ambiguous genitalia, open labia and atrophied right testicle while the leftremained in the pelvis, both were extirpated at 3 and 6 months of life respectively. A reviewof the literature was carried out and we proposed genetic counseling appropriate to thefindings in the karyotype.

Monosomía del brazo largo del cromosoma 9 en una paciente con sospecha de Síndrome de Turner. Reporte de caso / Monosomy of long arm or chromosome 9 in patients with suspicion of Turner Syndrome. Case report

Las alteraciones cromosómicas ocurren con una frecuencia de 1 por cada 150 recién nacidos vivos, generalmente no son hereditarias y la mayoría se caracteriza por expresar complejos fenotipos constituidos por malformaciones congénitas asociadas a retardo mental. Entre los portadores de alteraciones numéricas, aquellos con un cromosoma extra son los más frecuentes; las monosomías totales son incompatibles con la vida, excepto la del cromosoma X. Se presenta el caso de una niña de trece días de vida, internada en el servicio de pediatría del Hospital Central del Instituto de Previsión Social, por un cuadro de ictericia, cianosis y distress respiratorio, que ingresa a incubadora con oxígeno. Al examen físico presentó malformaciones congénitas diversas, con sospecha clínica de ser portadora de Síndrome de Turner. Se solicita el estudio cromosómico, el cual es realizado en sangre periférica, observándose en el 5% (3/60) de las células analizadas una deleción de todo el brazo largo de uno de los cromosomas del par 9, en mosaico. El cariotipo resultó 46,XX,[57]/46,XX,del(9)(q11.1 qter)[3]. Se resalta la necesidad de realizar el estudio cromosómico en recién nacidos con malformaciones diversas, para descartar o confirmar el diagnóstico presuntivo, a fin de tomar las medidas de tratamiento pertinentes y brindar el asesoramiento genético adecuado a los padres.

Chromosomal abnormalities occur with a frequency of 1 in 150 live newborns. They aregenerally not hereditary and most of them are characterized by expressing complexphenotypes consisting in congenital malformations associated with mental retardation.Among the carriers of numerical alterations, those with an extra chromosome are themost common and total monosomies are incompatible with life, except that of the Xchromosome. This is the case of a 13-day girl admittedinto a pediatrics service due tojaundice, cyanosis and respiratory distress, entering oxygen incubator. On physicalexamination, the girl presented various congenital malformations with clinical suspicion ofbeing a carrier of Turner syndrome. A chromosomal study, performed in peripheral blood,was requested and a deletion of the complete long arm of one of the chromosomes of pair9, in mosaic, was observed in 5% (3/60) of the analyzed cells. The karyotype was46,XX[57]/46,XX,del(9)(q11.1qter)[3]. The need of chromosomal studies in newbornswith various malformations is highlighted, in order to rule out or confirm the presumptivediagnosis and take the appropriate measures of treatment and provide adequate geneticcounseling to parents.

Monosomía 11 q compatible con síndrome de Jacobsen. Reporte de caso / 11 q monosomy compatible with Jacobson syndrome. Case report

Se reporta el caso de una niña de 13 días de vida, con una deleción distal del brazo largo del cromosoma 11, nacida de madre portadora de un cromosoma marcador y de una inversión pericéntrica de la heterocromatina del cromosoma 9, la cual también se hallaba presente en la propósita. El cariotipo de la niña resultó 46,XX, del(11)(q24 ­11qter), inv 9qh.La madre de la niña, con fenotipo normal, presentó un cariotipo 46,XX/47,XX+mar, inv9qh. El cariotipo del padre de la propósita fue normal. En este reporte destacamos la importancia de realizar el diagnóstico cromosómico en niños portadores de múltiples malformaciones y también la de efectuar el análisis cromosómico a los padres para el pronóstico del caso y asesoramiento genético de la pareja.

This is the case of a 13-day girl with a distal deletion of the long arm of chromosome 11 and a pericentric inversion of the heterochromatin of chromosome 9. Her mother also had a pericentric inversion of the heterochromatin of chromosome 9 and a chromosome marker. The cariotype of the affected girl was 46, XX, del (11) (q24 ­11qter), inv 9qh and the cariotype of the mother, with normal phenotype, was 46,XX,/47,XX+mar, inv 9qh. The mother of the proband had a normal phenotype. This paper highlights the importance of making an accurate chromosomal diagnosis in a child with multiple malformations as well as the importance of making a chromosomal analysis of the parents to make the case prognosis and proper genetic counselling.

Duplicación distal del brazo largo del cromosoma 3 en línea pura: a propósito de un caso / Distal duplication of the long arm of chromosome 3

Se reporta el caso de una niña de 25 días de vida con una duplicación distal del brazo largo del cromosoma 3, lo cual ocasiona una trisom¡a 3q2, enfermedad cromosómica muy rara. Los síntomas más importantes que presentan estos individuos, incluyen entre otros, retraso pre y post natal del crecimiento, retraso mental severo, microcefalia, sinofrismo, hipertricosis, malformaciones del corazón, de los riñones y de otros órganos internos y ocasionalmente anomalías de los miembros. El estudio cromosómico se llevó a cabo en sangre periférica, con técnicas de coloración convencional y de identificación con Bandas G y C. El cariotipo de la paciente resultó: 46,XX,dup3(q25→qter). El análisis cromosómico de los padres fue normal. Las características clínicas observadas inicialmente en la niña fueron compatibles con el Síndrome de Beckwith-Wiedeman y el de Cornelia de Lange, descartados a través del estudio citogenético, es por ello que se resalta la importancia del estudio cromosómico en el diagnóstico diferencial de síndromes de origen génico, para el diagnóstico de certeza y el asesoramiento genético a los padres.

This report is on a girl of 25 years old with a distal duplication of the long arm of chromosome 3. Trisomy 3q is a rare disease caused by the duplication of the long arm of chromosome 3. The most important signs of the disease includes pre and post-natal growth delay, severe mental retard, microcephaly, synophrism, hypertrichosis, heart, kidney and other organs malformations among others and occasionally limbs anomaly. The chromosome study was carried out in peripheral blood with conventional staining techniques andGC and C band identification. The cariotype of the patient was 46, XX, dup 3 (q25 qter) while the cariotypes of the parents were normal. The clinical characteristics were also compatible with Beckwith-Wiedeman and Cornelia de Lange syndromes that were discarded by chromosome analysis. We highlight in this paper the importance of making an accurate chromosome study in the differential diagnosis of genetic origin syndromes for the certainty diagnosis and genetic counseling to parents.