Prenatal diagnosis of three fetuses with small supernumerary marker chromosomes / 中华医学遗传学杂志

OBJECTIVE@#To explore the origin and mechanism of small supernumerary marker chromosomes (sSMC) in three fetuses.@*METHODS@#The three fetuses were predicted to have carried chromosomal abnormalities by non-invasive prenatal testing (NIPT). G-banding chromosomal karyotyping analysis were carried out on amniotic fluid samples of the fetuses and peripheral blood samples from their parents. Single nucleotide polymorphism array (SNP-array) was used to determine the origin, size and genetic effect of sSMCs.@*RESULTS@#In fetus 1, SNP array has detected two microduplications respectively at 4p16.3p15.2 (24.7 Mb) and 18p11.32q11.2 (20.5 Mb) which, as verified by fluorescence in situ hybridization (FISH), have derived from a balanced 46,XY,t(4;18)(p15.2q11.2) translocation carried by its father. Fetus 2 has carried a de novo microduplication of 15q11.2-q13.3 (9.7 Mb). The sequence of SMC in fetus 3 has derived from 21q11.2-q21.1 (8.3 Mb), which was inherited from its mother.@*CONCLUSION@#Both NIPT and SNP-array are highly accurate for the detection of sSMC. SNP-array can delineate the origin and size of abnormal chromosomes, which in turn can help with clarification of sSMC-related genotype-phenotype correlation and facilitate prenatal diagnosis and genetic counseling for the family.

CCAAT/enhancer-binding protein alpha (CEBPA) gene haploinsufficiency does not alter hematopoiesis or induce leukemia in Lck-CALM/AF10 transgenic mice

Although rare, CALM/AF10 is a chromosomal rearrangement found in immature T-cell acute lymphoblastic leukemia (T-ALL), acute myeloid leukemia, and mixed phenotype acute leukemia of T/myeloid lineages with poor prognosis. Moreover, this translocation is detected in 50% of T-ALL patients with gamma/delta T cell receptor rearrangement, frequently associated with low expression of transcription factor CCAAT/enhancer-binding protein alpha (CEBPA). However, the relevance of CEBPA low expression for CALM/AF10 leukemogenesis has not yet been evaluated. We generated double mutant mice, which express the Lck-CALM/AF10 fusion gene and are haploinsufficient for the Cebpa gene. To characterize the hematopoiesis, we quantified hematopoietic stem cells, myeloid progenitor cells, megakaryocyte-erythrocyte progenitor cells, common myeloid progenitor cells, and granulocyte-macrophage progenitor cells. No significant difference was detected in any of the progenitor subsets. Finally, we tested if Cebpa haploinsufficiency would lead to the expansion of Mac-1+/B220+/c-Kit+ cells proposed as the CALM/AF10 leukemic progenitor. Less than 1% of bone marrow cells expressed Mac-1, B220, and c-Kit with no significant difference between groups. Our results showed that the reduction of Cebpa gene expression in Lck-CALM/AF10 mice did not affect their hematopoiesis or induce leukemia. Our data corroborated previous studies suggesting that the CALM/AF10 leukemia-initiating cells are early progenitors with lymphoid/myeloid differentiating potential.

Clinical features of carriers of reciprocal chromosomal translocations involving chromosome 2: report of nine cases and review of the literature

ABSTRACT Objective: To explore the clinical features of carriers of chromosome 2 translocations, enabling informed genetic counseling of these patients. Materials and Methods: Eighty-two male carriers of a translocation who were infertile or receiving fertility counseling were recruited. Cytogenetic analyses were performed using G-banding. A search of PubMed was performed to determine whether the identified translocations on chromosome 2 are involved in male infertility. The relationships of translocation breakpoints with male infertility and recurrent pregnancy loss were analyzed. Results: Of the 82 translocation carriers, 9 (11%) were carriers of a chromosome 2 translocation. Four cases had oligozoospermia or infertility, while five had normal semen. In an analysis of the literature, 55 patients who were carriers of chromosome 2 translocations were also reviewed. Breakpoints at 2p13 and 2q31 were observed in six patients each, and were the most common. Breakpoints at 2p23, 2p13, 2p11.2, 2q31, and 2q37 were associated to both pre-gestational and gestational infertility, while other breakpoints were associated with gestational infertility. Conclusions: All breakpoints at chromosome 2 were correlated with gestational infertility. Carriers of chromosome 2 translocations should therefore receive counseling to continue with natural conception and use of different technologies available via assisted reproductive technology, such as preimplantation genetic diagnosis.

Hipercalcemia, peak monoclonal y leucemización como presentación de un linfoma de células B de alto grado, con reordenamiento de MYC, BCL-2 y BCL-6 (Triple Hit). Caso clínico / Hypercalcemia, monoclonal peak and leukemic presentation of a High-grade B-cell lymphoma with MYC, BCL-2 and BCL-6 translocations (triple hit). Report of one case

High-grade B-cell lymphomas with rearrangement of MYC, BCL-2 and/or BCL-6 were introduced by the update of the WHO classification of lymphoid neoplasms. They usually present unique morphological and molecular characteristics, with an aggressive clinical outcome and worse prognosis. We report a 48 year-old female patient presenting with B symptoms and enlarged lymph nodes. Blood count showed pancytopenia and peripheral blood smears showed large lymphoid cells, some with nuclei and vacuoles. LDH was 3524 g/L and serum calcium was 11.5 mg/dL. Flow cytometry immunophenotyping showed pathological mature B lymphocytes. Protein electrophoresis showed a slight monoclonal peak. The biopsy disclosed a triple expressor diffuse large B-cell lymphoma, arising from germinal center. FISH was positive for MYC, BCL-2 and BCL-6 (triple hit) with a clonal evolution. Conventional cytogenetics showed a complex karyotype. Chemotherapy was started with R-CHOP (Rituximab/cyclophosphamide/doxorubicin/vincristine/prednisone). She developed impaired consciousness; the brain CT scan showed a large brain mass. The patient died within 3 weeks.

Runx1-Runx1t1: comportamiento en pacientes con leucemia mieloide aguda en nuestro medio / Runx1-Runx1t1: behavior in patients with acute myeloid leukemia

El continuo desarrollo molecular ha restado protagonismo a otras clasificaciones de la leucemia mieloide aguda (LMA) basadas en la morfología e histoquímica general. En el caso de la LMA existe un subtipo donde el gen AML1 (RUNX1), esencial para la normal hematopoyesis, se fusiona con el gen co-represor transcripcional ETO (RUNX1T1) generando una proteína anormal con múltiples efectos en la mielopoyesis. Se analizó el comportamiento de este gen de fusión en 174 pacientes con LMA, estudiados por reacción en cadena de la polimerasa con reverso transcripción (RT-PCR) en el laboratorio de Biología Molecular del Instituto de Hematología e Inmunología (IHI) entre enero del 2000 y agosto del 2013. El 13,8 por ciento (24 pacientes) fue positivo al RUNX1-RUNX1T1. En dicho grupo la edad osciló entre los 3 y los 62 años, con una media de 20,9 años aunque la mayor incidencia fue en pacientes de edad pediátrica (1-19 años) con un 66,7 por ciento Predominó el sexo masculino y el color de la piel no blanca con 62,5 por ciento y 58,3 por ciento respectivamente. De estos pacientes, el 37,5 por ciento presentaron un diagnóstico morfológico de M2, el 12,5 por ciento de M4 y la mitad de los casos 50 por ciento habían tenido un diagnóstico al debut, sugestivo de leucemia promielocítica (LPM); a este último grupo se le determinó la presencia del gen quimérico PML/RARα, para los que fueron negativos, demostrándose posteriormente el RUNX1-RUNX1T1. En un solo paciente se encontró la asociación de la duplicación interna en tándem (DIT) del FLT3 con el RUNK1-RUNX1T1. La confirmación de la presencia del gen de fusión RUNX1-RUNX1T1 en pacientes con morfología M3, confirma una vez más que las técnicas moleculares son de vitales para el diagnóstico de la LMA y la morfología se va relegando a los casos donde la citogenética y la biología molecular a día de hoy no logren definir una alteración genética. Introducción: el continuo desarrollo molecular ha restado protagonismo a otras clasificaciones de la leucemia mieloide aguda (LMA) basadas en la morfología e histoquímica general. En el caso de la LMA existe un subtipo donde el gen AML1 (RUNX1), esencial para la hematopoyesis normal, se fusiona con el gen correpresor transcripcional ETO (RUNX1T1) nó el sexo masculino (62,5 por cientoy el color de la piel no blanca (58,3 por ciento). El 37,5 por ciento de los pacientes presentó diagnóstico morfológico de M2, el 12,5 por ciento de M4, y el 50 por ciento había tenido un diagnóstico al debut sugestivo de leucemia promielocítica; posteriormente se demostró el RUNX1 - RUNX1T1. En el 8,3 por ciento de los pacientes positivos al RUNX1 - RUNX1T1 se encontró asociación con la duplicación interna en tándem (DIT) del FLT3. Conclusiones: la presencia del gen de fusión RUNX1-RUNX1T1 en pacientes con morfología M3, confirma una vez más que las técnicas moleculares son de vital importancia para el diagnóstico de la LMA y la morfología se va relegando a los casos donde la citogenética y la biología molecular no logren definir una alteración genética(AU)

Introduction: the molecular development has reduced importance to other classifications of acute myeloid leukemia (AML) based on morphology and general histochemistry. When AML1 (RUNX1) gene, essential for normal hematopoiesis, is fused to the transcriptional co-repressor ETO (RUNX1T1) gene, an abnormal protein with multiple effects on myelopoiesis is synthesized. Objective: analyze the behavior of the fusion gene RUNX1 - RUNX1T1 in our patients. Methods: this fusion gene was evaluated in 174 patients with AML studied by polymerase chain reaction with reverse transcription (RT - PCR) at the laboratory of Molecular Biology of the Institute of Hematology and Immunology (IHI), between January 2002 and August 2013. Results: twenty four patients (13,8 percent) were positive to RUNX1-RUNX1T1. In this group age ranged from 3 to 62 years with a mean of 20.9 years, although the incidence was higher in pediatric patients (1 - 19 years), 66,7 percent. Males and non-white individuals were predominant with 62,5 percent and 58,3 percent respectively. Of these patients, 37,5 percent had a morphological diagnosis of AML M2; 12,5 percent of M4; and half of the patients (50 percent) had a diagnosis suggestive of promyelocytic leukemia (PML). In the latter group, the presence of the chimeric gene PML / RARα was determined; all these patients were negative for this fusion gene and later the RUNX1 - RUNX1T1 was demonstrated. The association of internal tandem duplication (ITD) - FLT3 with RUNK1 - RUNX1T1 was found in 8,3 percent. Conclusions: the fusion gene RUNX1 - RUNX1T1 in patients with morphological appearance of M3, once again confirms that molecular techniques are vital for the diagnosis of AML and morphology is relegated to cases where cytogenetic and molecular biology fails to define a genetic alteration(AU)

Constitutional Chromosomal Abnormality Identified in a Sibling Donor After Bone Marrow Stem Cell Transplantation in a Pediatric Patient with Acute Megakaryoblastic Leukemia

No abstract available.

HELICOBACTER PYLORI AND t(11;18)(q21;q21) TRANSLOCATION IN GASTRIC MALT LYMPHOMA / Helicobacter pylori e presença de translocação t(11;18)(q21;q21) em pacientes portadores de linfoma MALT gástrico

Context Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is clearly associated with Helicobacter pylori gastritis and can be cured with anti- H pylori therapy alone. The presence of t(11;18)(q21;q21) translocation is thought to predict a lower response rate to anti- H pylori treatment. Objectives To study the presence of t(11;18)(q21;q21) genetic translocation and its clinical impact in low-grade gastric MALT lymphoma Brazilian patients. Methods A consecutive series of eight patients with gastric MALT lymphoma were submitted to gastroscopy, endoscopic ultrasound, histopathological examination, H pylori search and RT-PCR-based methodology. All patients received anti-H pylori treatment. Eradicated patients were followed-up every 3-6 months for 2 years. Results Eight patients were studied. All patients had tumor involvement restricted to the mucosa or submucosa and seven patients had low-grade gastric MALT lymphoma. All infected patients achieved H pylori eradication. Histological tumor regression was observed in 5/7 (71%) of the low-grade gastric MALT lymphoma patients. The presence of t(11;18)(q21;q21) translocation was found in 4 (57%) of these patients; among them only two had histological tumor regression following H pylori eradication. Conclusions RT-PCR is a feasible and efficient method to detect t(11;18)(q21;q21) translocation, being carried out in routine molecular biology laboratories. The early detection of such translocation can be very helpful for better targeting the therapy to be applied to gastric MALT lymphoma patients. .

Contexto A patogênese do linfoma MALT (tecido linfoide associado à mucosa) gástrico, também conhecido como linfoma de zona marginal de células B, está claramente associada à gastrite por infecção pelo Helicobacter pylori e, a maioria desses tumores pode ser curada apenas com a erradicação da bactéria. A presença da translocação t(11;18)(q21;q21) tem sido identificada como a anomalia citogenética mais comum do linfoma MALT gástrico e sua presença pode prever uma menor taxa de resposta ao tratamento anti-H pylori. Objetivos Estudo da translocação genética t(11;18)(q21;q21) e seu impacto na evolução clínica de pacientes portadores de linfoma MALT gástrico de baixo grau. Métodos Uma série consecutiva de oito pacientes com linfoma MALT gástrico foi submetida à endoscopia digestiva, ultra-sonografia endoscópica, exame histopatológico, pesquisa do H pylori e metodologia rotineira de transcrição reversa seguida de reação em cadeia da polimerase (RT-PCR) utilizando primers específicos para API2-MALT1. Todos os pacientes receberam tratamento anti-H pylori e retratamento, quando necessário. Após a erradicação, exames endoscópicos foram realizados a cada 3-6 meses durante 2 anos para acompanhamento da evolução do tumor. Resultados Foram estudados oito pacientes (seis mulheres, idade média: 57 anos). Todos apresentavam à ecoendoscopia envolvimento tumoral restrito à mucosa ou submucosa com aparência endoscópica variável. A histologia mostrou que sete pacientes tinham linfoma MALT gástrico de baixo grau e um de alto grau. A erradicação do H pylori foi obtida em todos os pacientes, embora a bactéria não tenha sido identificada em um deles. Foi observada regressão histológica ...

Sinaptogénesis y esquizofrenia: rol de la proteína DISC 1 / Synaptogenesis and Schizophrenia: The role of DISC 1 protein

El presente trabajo aporta información respecto del posible rol en la esquizofrenia del gen DISC 1 y la proteína que este gen codifica. Se realiza un recorrido desde el hallazgo de la translocación cromosómica que llevó a su descubrimiento, hasta la perspectiva actual, que lo conceptualiza como un modulador funcional complejo. La mencionada translocación fue originariamente identificada en una familia escocesa, y se observó que cosegregaba con esquizofrenia y otros trastornos mentales. Actualmente, se considera a DISC 1 como una proteína central dentro de una red de interacciones con otras proteínas - lo que en varios trabajos se denomina interactoma -, tales como NDEL 1, LIS 1 y PDE 4B, entre otras.

This paper provides information regarding the possible role in schizophrenia of the DISC 1 gene and the protein it encodes. It is a tour from the discovery of the chromosomal translocation that led to its discovery, up to the current perspective, which is conceptualized as a complex functional modulator. The above translocation was originally identified in a Scottish family, and it was noted that it cosegregated with schizophrenia and other mental discorders. Currently, DISC 1 is considered as a central protein within its network of protein interactions (named as interactome in several papers), such as NDEL 1, LIS 1 and PDE 4B, among others.

Unexpected Inheritance of a Balanced Homologous translocation t(22q;22q) from father to a phenotypically normal daughter.

Rearrangements between homologous chromosomes are extremely rare and manifest mainly as monosomic or trisomic offsprings. There are remarkably few reports of balanced homologous chromosomal translocation t (22q; 22q) and only two cases of transmission of this balanced homohologous rearrangement from mother to normal daughter are reported. Robersonian translocation carriers in non‑homologous chromosomes have the ability to have an unaffected child. However, it is not possible to have an unaffected child in cases with Robersonian translocations in homologous chromosomes. Carriers of homologous chromosome 22 translocations with maternal uniparental disomy do not have any impact on their phenotype. We are presenting a family with a history of multiple first trimester miscarriages and an unexpected inheritance of balanced homologous translocation of chromosome 22 with paternal uniparental disomy. There are no data available regarding the impact of paternal UPD 22 on the phenotype. We claim this to be the first report explaining that paternal UPD 22 does not impact the phenotype.

A rare non-Robertsonian translocation involving chromosomes 15 and 21 / Uma rara translocacao nao robertsoniana envolvendo os cromossomos 15 e 21

CONTEXT: Robertsonian translocations (RT) are among the most common balanced structural rearrangements in humans and comprise complete chromatin fusion of the long arm of two acrocentric chromosomes. Nevertheless, non-Robertsonian translocation involving these chromosomes is a rare event. CASE REPORT: We report a de novo unbalanced translocation involving chromosomes 15 and 21. The newborn was the daughter of a 29-year-old mother and a 42-year-old father. The couple was non-consanguineous. Clinical findings led to the diagnosis of Down syndrome (DS) with severe congenital heart defects (persistent arterial duct, and complete atrioventricular septal defect), as well as low birth length and weight (< 5th and < 10th percentile, respectively, based on specific measurement curves for DS). Conventional cytogenetic analysis revealed the karyotype 46,XX,der(15)(15pter→15q26.2::21q11.2→21qter). The translocation was confirmed by means of fluorescence in situ hybridization. The parents had normal karyotypes. CONCLUSIONS: Differently from RT, in our case a rare event occurred involving the distal segment of 15q and the proximal segment of 21q. Only two reports of this translocation, involving chromosomes 15 and 21 but different breakpoints, have been described so far. The association between 21q duplication and 15q deletion makes it difficult to separate the effect of each chromosome, but might also be responsible for increasing the growth retardation, as detected in our case. Cytogenetic analysis on DS patients is mandatory not only to confirm the diagnosis, but also to assess the risk of recurrence at genetic counseling, as well as to evaluate the contribution of other chromosome aberrations in the final phenotype. .

CONTEXTO: Translocações robertsonianas (TR) estão entre os rearranjos estruturais balanceados mais comuns em humanos e compreendem a fusão da cromatina completa do braço longo de dois cromossomos acrocêntricos. No entanto, são raras as translocações não Robertsonianas envolvendo esses cromossomos. RELATO DE CASO: Nós descrevemos uma translocação não balanceada de novo envolvendo os cromossomos 15 e 21. A recém-nascida era filha de uma mãe de 29 anos e de um pai de 42 anos, casal não consanguíneo. Os achados clínicos levaram ao diagnóstico de síndrome de Down (SD) com defeitos cardíacos congênitos graves (persistência do canal arterial e defeito do septo atrioventricular completo), além de baixos comprimento e peso ao nascimento (< 5o e < 10o percentil em curvas de medidas específicas para SD, respectivamente). A análise citogenética convencional revelou o cariótipo 46,XX,der(15)(15pter→15q26.2::21q11.2→21qter). A translocação foi confirmada por hibridação in situ fluorescente. Os pais apresentavam cariótipo normal. CONCLUSÕES: Diferentemente das TR, nesse caso ocorreu evento raro envolvendo o segmento distal de 15q e o proximal de 21q. Apenas dois relatos dessa translocação, envolvendo os cromossomos 15 e 21 e diferentes pontos de quebra, já foram descritos. A associação entre duplicação 21q e deleção 15q dificulta a distinção dos efeitos de cada cromossomo, mas poderia também ser responsável pelo acentuado retardo de crescimento. A análise citogenética é obrigatória em pacientes com SD não apenas para confirmar o diagnóstico, mas também para avaliar o risco de recorrência no aconselhamento genético, bem como avaliar a contrib...

Transient neonatal hypothyroidism in a boy with unbalanced translocation t(8;16) / Hipotireoidismo neonatal transitório em um menino com translocação não balanceada t(8;16)

Genetic defects resulting in deficiency of thyroid hormone synthesis can be found in about 10% of the patients with permanent congenital hypothyroidism, but the identification of genetic abnormalities in association with the transient form of the disease is extremely rare. We report the case of a boy with transient neonatal hypothyroidism that was undiagnosed in the neonatal screening, associated with extrathyroid malformations and mental retardation. The boy carries an unbalanced translocation t(8;16), and his maternal uncle had a similar phenotype. Chromosomal analysis defined the patient's karyotype as 46,XY,der(8)t(8;16)(q24.3;q22)mat,16qh+. Array-CGH with patient's DNA revealed a ~80 kb terminal deletion on chromosome 8q24.3qter, and a ~21 Mb duplication on chromosome 16q22qter. ZNF252 gene, mapped to the deleted region on patient's chromosome 8, is highly expressed in the thyroid, and may be a candidate gene for our patient's transient neonatal thyroid dysfunction. This is the first report on the association of a chromosomal translocation with the transient form of congenital hypothyroidism. This description creates new hypothesis for the physiopathology of transient congenital hypothyroidism, and may also contribute to the definition of the unbalanced translocation t(8;16)(q24.3;q22) phenotype, which has never been described before. Arq Bras Endocrinol Metab. 2012;56(8):564-9.

Defeitos genéticos resultando em deficiência hormonal tireoidiana podem ser encontrados em cerca de 10% dos pacientes com hipotireoidismo congênito permanente, porém a identificação de anormalidades genéticas associadas à forma transitória da doença é extremamente rara. Relatamos o caso de um menino com hipotireoidismo neonatal transitório não diagnosticado no teste de triagem neonatal, associado a malformações extratireoidianas e retardo mental. O paciente é portador de translocação não balanceada t(8;16), e seu tio materno tinha fenótipo similar. A análise cromossômica definiu o cariótipo do paciente como 46,XY,der(8)t(8;16)(q24.3;q22)mat,16qh+. A análise cromossômica array-CGH com o DNA do paciente revelou deleção terminal de ~80 kb no cromossomo 8q24.3qter, e duplicação de ~21 Mb no cromossomo 16q22qter. O gene ZNF252, mapeado na região da deleção no cromossomo 8 do paciente, é altamente expresso na tireoide e pode ser um gene candidato no hipotireoidismo neonatal transitório do paciente. Esse é o primeiro relato de associação de uma translocação cromossômica com a forma transitória do hipotireoidismo congênito. Essa descrição descortina novas hipóteses para a fisiopatologia do hipotireoidismo congênito transitório e também pode contribuir para a definição do fenótipo da translocação não balanceada t(8;16)(q24.3;q22), nunca descrito anteriormente. Arq Bras Endocrinol Metab. 2012;56(8):564-9.

Genetic counseling in carriers of reciprocal translocations involving two autosomes.

One of the main genetic causes involve in the pathogenesis of recurrent abortion is parental chromosomal abnormalities. The central concept in genetic counseling with such families is to estimate the probability of recurrence of unfavorable pregnancy outcomes. The main questions that consultants usually ask are: Why did this happen? What is the risk to be done again? Our cases were two families with repeated miscarriage. The pedigrees were drawn, the chromosomes of couples were studied, and estimation for recurrent risk was done. We tried to answer those two main questions and clear the results for them. Parental chromosome abnormalities were founded after karyotyping with GTG technique at 450 band resolution, revealing 46 chromosomes with balanced translocation of autosomes in one of the partner in both families. Recurrent risk was estimated as "high" for their future pregnancies in each family. Couples in which one partner is the carrier of such balanced translocation have increased risks of infertility, recurrent abortion, and delivery of chromosomally abnormal offspring. Genetic counseling of such couples, therefore, presents a unique challenge and should be considered in dealing with such families.

Diagnóstico clínico y molecular de síndrome de cefalopolisindactilia de Greig. A propósito de un caso. / Clinical and molecular cephalopolysyndactyly Greig syndrome. A case report

El síndrome de cefalopolisindactilia de Greig (SCPG) es una afección autosómica dominante caracterizada por polidactilia o sindactilia de manos y pies, macrocefalia, hipertelorismo y ocasionalmente anomalías cerebrales y retraso mental. Es un síndrome poco frecuente, heredado según un patrón autosómico dominante. La prevalencia es ignorada, siendo conocidos 100 casos aproximadamente. Más del 75 % de los pacientes con manifestaciones clínicas características de SCPG presentan mutaciones en el gen GLI3. El diagnóstico presuntivo de SCPG puede realizarse cuando el paciente presenta la tríada clásicade polidactilia, hipertelorismo y macrocefalia, siendo indicativo para la realización del análisis molecular del gen GLI3. En este trabajo se describe el caso de un niño referido al Instituto de Genética Médica con diagnóstico clínico de polidactilia y macrocefalia. Las características clínico-evolutivas e imagenológicas del paciente permitieron postular el diagnóstico de SCPG. El análisis molecular del gen GLI3 confirmó el diagnóstico de SCPG identificando la mutación c.1850_1852 del GTTinsAT (p.R617LfsX11) en el exón 12 del gen GLI3. Se trata de una mutación no descrita previamente como una mutación asociada al desarrollo de SCPG; no obstante, al tratarse de una mutación que provoca una proteína truncada desde el exón 12 del gen GLI3, no existen muchas dudas sobre su patogenicidad. Este resultado tiene implicaciones hereditarias y familiares permitiendo un adecuado asesoramiento genético en el contexto familiar.

Familial small supernumerary marker chromosome (sSMC) (14)(:p11-q11:) in a child with translocation down syndrome.

We report a case of familial small supernumerary marker chromosome (sSMC) in a child with translocation Down syndrome (DS)and mother.The GTG-banded chromosomal analysis of DS child revealed 47,XY,+21,+mar and mother karyotype was 47,XX,+mar.The GTG-banded sSMC had a similar morphology of small acrocentric chromosomes .Fluorescence in situ hybridization (FISH)evaluation of sSMC using centromere probes(13/21,14/22,22)confirmed sSMC as derivative chromosome 14.The sSMC was not specifically stained with whole chromosome paint and arm-specific probes for chromosome 14;thus it has been described as der(14)(:p11-q11:).The phenotypic changes were not evident, may be due to trisomy condition in the child or the sSMC contain repetitive sequences.

La genética como factor pronóstico y terapéutico en el mieloma múltiple: [revisión] / Genetic markers as prognostic factors in multiple myeloma: [revision]

The search for prognostic factors in multiple myeloma has identified the genetic profile of the tumor as the main determinant of patient survival and response to treatment. There is an association between a dismal prognosis and the presence of t(4:14) translocations or 17p deletion, determined by fluorescent in situ hybridization (FISH) or the detection of chromosome 13 deletion using conventional cytogenetic techniques. These alterations define a subpopulation that comprises 25% of patients with a bad prognosis even if they are treated with high dose chemotherapy. These patients should be early derived to more specific therapies. In the other hand, the other 75% of patients without a genetic risk factor, have a higher probability of success with conventional treatment.

Partial trisomy and partial monosomy resulting from a reciprocal segregating in a large family.

Partial trisomy 7p with partial monosomy 9p is a rare disorder with only 3 cases reported. Both these abnormalities i.e., partial trisomy 7p and partial monosomy 9p result in distinct clinical phenotypes. However, patients with combined 7p trisomy/9p monosomy present with a phenotype consistent with trisomy 7p. We present a fourth case of trisomy 7p/monosomy 9p with long term follow-up and document the medical complications associated with this disorder. Long term follow-up of patients with chromosome abnormalities provides a unique opportunity to document the medical history and complications associated with such abnormalities.