Outcomes of Preimplantation Genetic Diagnosis Cycles by Fluorescent Hybridization of Infertile Males with Nonmosaic 47,XYY Syndrome / 中华医学杂志(英文版)

Background@#The 47,XYY syndrome could result in fertility problems. However, seldom studies reported comprehensive researches on the embryonic development and pregnancy outcomes of these patients. This study aimed to evaluate the clinical outcomes of nonmosaic 47,XYY patients performed with fluorescent in situ hybridization (FISH) and preimplantation genetic diagnosis (PGD) treatment.@*Methods@#This was a retrospective study. Between January 2012 and May 2017, 51 infertile males with nonmosaic 47,XYY syndrome underwent FISH-PGD were included in the study. According to sex chromosomal FISH results, embryos were classified as normal signal, no nuclei fixed, no signal in fixed nuclei, suspensive signal, and abnormal signal groups, respectively. The incidence of each group, the fixation rate, and hybridization rate were calculated. Embryonic development and pregnancy outcomes were also analyzed. The measurement data were analyzed with Student's t-test. The comparison of categorical data was analyzed with the Chi-square test and Fisher's exact test when expected cell count was 0.05), and were significantly lower than the normal signal group (66.4%, P < 0.001). The clinical pregnancy rates of fresh and frozen embryos transferred cycles were 70.6% and 85.7%, respectively.@*Conclusions@#Among embryos with a clear diagnosis of sex chromosome, about one-fifth showed abnormal signals. Embryos with two sex chromosomal signals are more likely to develop into good-quality ones. The application of the PGD by FISH may help to improve the clinical outcome s.

Genetic analysis of a child with XYY syndrome mainly featuring mental retardation / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the genetic cause for a boy featuring mainly with mental retardation.</p><p><b>METHODS</b>G-banding karyotyping and fluorescence in situ hybridization (FISH) were carried out for the child and his parents. The child was also analyzed with chromosome microarray (CMA). Suspected microdeletion was validated with quantitative PCR.</p><p><b>RESULTS</b>The proband was found to have a 47,XYY karyotype by both chromosome and FISH analyses, while both of his parents had a normal karyotype. CMA suggested that the proband had one copy of X chromosome and two copies of Y chromosome. In addition, CMA has also detected deletion of the KYNU gene (mapped at 2q22.2), which could be pathogenic. The result was confirmed by qPCR.</p><p><b>CONCLUSION</b>For its high resolution, CMA can be used to identify potential microdeletion/duplications among children with chromosome aneuploidy and unusual phenotypes.</p>

Esthesioneuroblastoma in a boy with 47, XYY karyotype / 소아과

Neuroblastomas are sometimes associated with abnormal constitutional karyotypes, but the XYY karyotype has been rarely described in neuroblastomas. Here, we report a case of an esthesioneuroblastoma in a boy with a 47, XYY karyotype. A 6-year-old boy was admitted to our hospital because of nasal obstruction and palpable cervical lymph node, which he first noticed several days previously. A polypoid mass in the right nasal cavity was detected through sinuscopy. Biopsy of the right nasal polyp was performed. Based on the result, the patient was diagnosed with a high-grade esthesioneuroblastoma. Nuclear imaging revealed increased uptake in both the right posterior nasal cavity and the right cervical IB-II space, suggesting metastatic lymph nodes. Cytogenetic analysis revealed a 47, XYY karyotype. Twelve courses of concurrent chemotherapy were administered. Three years after the completion of chemotherapy, the patient had had no disease recurrence. He manifested behavioral violence and temper tantrums, so we started methylphenidate for correction of the behavior.

Morphology and pathogenesis of 47, XYY/47, XY, +mar identified in patients with super male syndrome / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the source and morphology of supernumerary markers from patients with 47,XYY/47,XY, +mar and supermale syndrome.</p><p><b>METHODS</b>Conventional GTG banded karyotyping and dual-color fluorescence in situ hybridization (FISH) were performed on 21 such patients.</p><p><b>RESULTS</b>Among these cases, 18 had their small supernumerary marker derived from the Y chromosome. Three were derived from autosomal chromosomes. Those derived from Y chromosome were small fragments with centromeres, while those derived from autosomes were in the ring form.</p><p><b>CONCLUSION</b>In children with supermale syndrome and 47,XYY/47,XY,+ mar, the supernumerary marker chromosomes primarily derive from sex chromosomes. These small chromosomes mainly have the forms of small segments with centromeres or rings. For such children, molecular cytogenetic analysis can facilitate genetic counseling and prenatal diagnosis.</p>

Síndrome 47, XYY / 47, XYY Syndrome

A síndrome XYY é definida como uma aneuploidia de cromossomos sexuais, a qual o indivíduo recebe um cromossomo Y extra, apresentando cariótipo 47,XYY. A síndrome apresenta como características principais alta estatura na primeira infância, atraso na fala, dificuldade de leitura e concentração. A maioria dos homens XYY é fértil e não apresenta manifestações clínicas significativas e permanece sem diagnóstico O objetivo do presente trabalho é relatar o caso de um paciente de 12 anos afetado pela Síndrome 47,XYY.

XYY syndrome is defined as a sex chromosome aneuploidy, in which the individual receives an extra Y chromosome, presenting karyotype 47,XXY. The main features of the syndrome are tall stature in early childhood, delayed speech, and difficulty reading and concentrating. Most XYY males are fertile, show no significant clinical symptoms and remain undiagnosed. The aim of this study is to report the case of a 12-year-old patient affected by 47, XYY syndrome.

Genetic analysis of a family with super-male syndrome / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To identify the genetic cause for a family featuring language retardation using combined cytogenetic and molecular genetic methods.</p><p><b>METHODS</b>Following conventional G-banded karyotype analysis, the additional Y chromosome was identified by fluorescence in situ hybridization (FISH) and multiplex ligation dependent probe amplification (MLPA). Whole genome array comparative genomic hybridization (aCGH) was also carried out to detect minor structural chromosomal abnormalities.</p><p><b>RESULTS</b>The proband's karyotype was determined as 47,XY,+?, and the unknown aberrant chromosome was identified as Yqh+ with FISH, MLPA and aCGH. No other chromosomal abnormality was found in the pedigree.</p><p><b>CONCLUSION</b>Cytogenetic methods combined with FISH, MLPA, and aCGH can efficiently identify the origin of unknown chromosomes and provide accurate clues for clinical diagnosis and treatment.</p>

Talla alta, sindrome XYY: presentación de un caso / High -Class, XYY Syndrome: case report

Los niños y hombres con el síndrome 47 XYY tienen dos cromosomas Y en vez de uno. Esto significa que tienen 47 cromoso- mas en lugar de 46. El cromosoma adicional se obtuvo durante la formación del esperma que se juntó con el óvulo al formar el feto o durante el desarrollo temprano del feto, justo después de la concepción. El cromo - soma extra no puede ser removido nunca. El síndrome 47 XYY ocurre al azar. (1). Algunos médicos genetistas cuestionan si el uso del término «síndrome¼ es apropiado para ésta anomalía, porque el fenotipo es normal. (2). Las personas 47 XYY , presentan un aspecto físico normal, y se caracterizan por una estatura alta, que se hace más evidente en la adolescencia. (1, 2, 3)...(AU)

Doble aneuploidía en un niño colombiano: síndrome de Down-Klinefelter, con fenotipo de síndrome de Down / Double aneuploidy in a Colombian child: Down-Klinefelter syndrome with Down syndrome phenotype

La ocurrencia de una doble aneuploidía en una misma persona es un evento relativamente raro. Se presenta el caso de un niño de siete meses de edad, de padres no consanguíneos con características clínicas de síndrome de Down y cariotipo 48XXY.

The occurrence of double aneuploidy in one person is a relatively rare phenomenon. We report the case of a 7-month-old child, the third-born of non-consanguineous parents, with clinical features of Down syndrome and karyotype 48XXY.

Perfil lipídico en un grupo de pacientes con síndrome de Turner en la clínica Universitaria Bolivariana de laciudad de Medellín entre los años 2000-2009 / Lipid profile in a group of patients with Turner’s syndrome at clínica Universitaria Bolivariana in the Medellín city between 2000 and 2009

Introduction: Turner syndrome patients can present lipid profile alterations, which associated with obesity, frequent in these patients, causes increased cardiovascular risk, lowering their life expectancy. This research evaluates lipid profiles of patients with Turner syndrome between 2000 and 2009 and these are associated to the karyotype and other risk factors for coronary disease.Objective: To describe the lipid profile and other cardiovascular risk factors in a group of girls with Turner syndrome.Methods: This is a descriptive and retrospective study, which evaluated the clinical records of 21 girls with Turner syndrome. We sought metabolic risk factors for coronary disease such as lipid profile, weight, body mass index, and blood pressure.Results: Age at time of diagnostics ranged between 8 months to 17 years, four patients were below 10 years of age and 17 patients were over 11 years of age. The karyotype revealed: 57.3% with 45x monosomy, 33% with 46xx-45x mosaicism, and 9.5% with 46x-qx mosaicism. None of the patients was obese; the total cholesterol levels ranged from 116 mg/dl to 225 mg/dl with a mean of 168.7. When these patients were grouped by age, we found that 25% of those younger than 10 years of age had high levels of cholesterol vs. 58.8% for those over 10 years of age. Regarding the karyotype of the six patients with 46xx-45x karyotype, five (71.4%) presented hypercholesterolemia; 95.2% of the patients were normotensive.Discussion: This research revealed Turner syndrome patients present lipid profile alterations at early ages.Conclusion: It is important to include in the follow up protocol in these patients the lipid profile control and, thus, be able to conduct early interventions to improve their quality of life.

Introducción: Las pacientes con síndrome de Turner (ST) pueden presentar alteraciones en el perfil lipídico, lo que, asociado con la obesidad, frecuente en estas pacientes, produce un aumento del riesgo cardiovascular y reduce su esperanza de vida. En este estudio se evalúan los niveles de perfil lipídico en pacientes con ST entre 2000-2009, y se asocia con el cariotipo y otros factores de riesgo para enfermedad coronaria.Objetivos: Describir el perfil lipídico en un grupo de niñas con ST y otros factores de riesgo cardiovascular. Metodología: Estudio descriptivo, retrospectivo, en el que se evaluaron las historias clínicas de 21 niñas con ST. Se buscaron factores de riesgo metabólico para enfermedad coronaria tales como perfil lipídico, peso, índice de masa corporal y cifras de presión arterial.Resultados: En el momento del diagnóstico la edad osciló entre los 8 meses y 17 años; cuatro pacientes eran menores de 10 años y 17 mayores de 11 años. El cariotipo fue: 57.3% con monosomía 45x, 33% mosaicismo 46xx-45x y 9.5% mosaicismo 46x-qx. Ninguna paciente presentó obesidad; los niveles de colesterol total oscilaron entre 116 mg/dl-225 mg/dl con una media de 168.7. Al agrupar estas pacientes por edad, se encontró que 25% de las menores de 10 años tenían niveles altos de colesterol vs. 58.8% de las mayores de 10 años. En relación con el cariotipo de las 6 pacientes con cariotipo 46xx-45x, 5 (71.4%) presentaron hipercolesterolemia; 95.2% eran normotensas. Discusión: Este estudio demostró que las pacientes con ST presentan alteración en su perfil lipídico desde edades tempranas.Conclusión: Es importante incluir en el protocolo de seguimiento de estas pacientes el control del perfil lipídico y así poder realizar intervenciones tempranas y poder mejorar su calidad de vida.

Frequency of Y chromosome microdeletions and chromosomal abnormalities in infertile Thai men with oligozoospermia and azoospermia / 亚洲男科学杂志(英文版)

<p><b>AIM</b>To investigate the possible causes of oligozoospermia and azoospermia in infertile Thai men, and to find the frequencies of Y chromosome microdeletions and cytogenetic abnormalities in this group.</p><p><b>METHODS</b>From June 2003 to November 2005, 50 azoospermic and 80 oligozoospermic men were enrolled in the study. A detailed history was taken for each man, followed by general and genital examinations. Y chromosome microdeletions were detected by multiplex polymerase chain reaction (PCR) using 11 gene-specific primers that covered all three regions of the azoospermic factor (AZFa, AZFb and AZFc). Fifty men with normal semen analysis were also studied. Karyotyping was done with the standard G- and Q-banding. Serum concentrations of follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL) and testosterone were measured by electrochemiluminescence immunoassays (ECLIA).</p><p><b>RESULTS</b>Azoospermia and oligozoospermia could be explained by previous orchitis in 22.3%, former bilateral cryptorchidism in 19.2%, abnormal karyotypes in 4.6% and Y chromosome microdeletions in 3.8% of the subjects. The most frequent deletions were in the AZFc region (50%), followed by AZFb (33%) and AZFbc (17%). No significant difference was detected in hormonal profiles of infertile men, with or without microdeletions.</p><p><b>CONCLUSION</b>The frequencies of Y chromosome microdeletions and cytogenetic abnormalities in oligozoospermic and azoospermic Thai men are comparable with similarly infertile men from other Asian and Western countries.</p>

A Dispermic Chimera with Mixed Field Blood Group B and Mosaic 46,XY/47,XYY Karyotype

Chimerism in humans is a rare phenomenon often initially identified in the resolution of an ABO blood type discrepancy. We report a dispermic chimera who presented with mixed field in his B antigen typing that might have been mistaken for the B3 subtype. The propositus is a healthy Korean male blood donor. Neither his clinical history nor initial molecular investigation of his ABO gene explained his mixed field agglutination with murine anti-B. Chimerism was suspected, and 9 short tandem repeat (STR) loci were analyzed on DNA extracted from blood, buccal swabs, and hair from this donor and on DNA isolated from peripheral blood lymphocytes from his parents. The propositus' red blood cells demonstrated mixed field agglutination with anti-B. Exon 6 and 7 and flanking intronic regions of his ABO gene were sequenced and revealed an O01/O02 genotype. B allele haplotype-specific PCR, along with exon 6 and 7 cloning and sequencing demonstrated a third ABO allele, B101. Four STR loci demonstrated a pattern consistent with a double paternal chromosome contribution in the propositus, thus confirming chimerism. His karyotype revealed a mosaic pattern: 32/50 metaphases were 46,XY and 18/50 metaphases demonstrated 47,XYY.

Genetic and epigenetic risks of intracytoplasmic sperm injection method / 亚洲男科学杂志(英文版)

Pregnancies achieved by assisted reproduction technologies, particularly by intracytoplasmic sperm injection (ICSI) procedures, are susceptible to genetic risks inherent to the male population treated with ICSI and additional risks inherent to this innovative procedure. The documented, as well as the theoretical, risks are discussed in the present review study. These risks mainly represent that consequences of the genetic abnormalities underlying male subfertility (or infertility) and might become stimulators for the development of novel approaches and applications in the treatment of infertility. In addition, risks with a polygenic background appearing at birth as congenital anomalies and other theoretical or stochastic risks are discussed. Recent data suggest that assisted reproductive technology might also affect epigenetic characteristics of the male gamete, the female gamete, or might have an impact on early embryogenesis. It might be also associated with an increased risk for genomic imprinting abnormalities.

Gen SRY y ausencia de tejido testicular en una mujer 47XYY con disgenesia gonadal / Gen SRY and absence of testicular tissue in a woman 47XYY with gonadal dysgenesis

Este artículo revisa conceptos actuales sobre determinación y diferenciación sexual con base en el estudio genético de una niña de 13 años que consultó por talla baja y aumento de peso. El examen físico mostró Tanner I en mamas y en vello púbico, sin signos de androgenización. Mientras el nivel de la hormona de crecimiento (GH) era normal, las hormonas folículoestimulante (FSH) y luteinizante (LH) estaban aumentadas. Mediante laparoscopia y posterior estudio patológico se demostró la presencia de gonadas rudimentarias con ausencia de tejido testicular. Aunque el cariotipo obtenido fue 47XYY y el análisis molecular identificó la presencia del gen SRY, su funcionalidad es incierta, lo que hace necesaria su secuenciación, con la finalidad de determinar posibles mutaciones. En respuesta a la terapia con estrógenos y progesterona se desarrollaron tanto los caracteres sexuales secundarios como una menstruación normal. Aunque es posible que en la paciente haya una doble alteración genética donde concurran la mutación de novo de un gen y una no disyunción en la meiosis paterna, el caso descrito es ilustrativo de la importancia del estudio genético en la evaluación de la disgenesia gonadal

Trisomy 21 with XYY.

A case of double aneuploidy involving chromosome 21 and Y is reported in an eight-month-old infant with developmental delay and failure to thrive. Patient had all classical phenotypical features of trisomy 21 except, absence of epicanthal folds. The diagnosis was confirmed by cytogenetic study performed on peripheral blood leucocyte culture using G-banding. Literature review revealed only 17 cases of XYY and trisomy 21 reported so far. No such case is reported in Indian literature. Relevant literature is reviewed and possible effects of trisomy 21 on XYY and that of XYY on trisomy 21 has been discussed. A routine chromosomal study even in patient with classical features of Down syndrome has been advocated. Interestingly, our patient also had left to right shunts at atrial and ductal level and tricuspid regurgitation. Given the rarity of the disorder and scanty published data the incidence, phenotype and recurrence risk are difficult to establish.

Actualización de síndrome de Down en el Instituto de Genética / Review about Down syndrome in the genetics institute

El presente documento contiene información sobre los aspectos más relevalentes que engloban a la cromosomopatía más frecuente, el Síndrome de Down (SD). Enfatizamos en la importancia de corroborar el diagnóstico clínico con el diagnóstico. Con el fin de tener una idea más concreta de la realidad actual en cuanto al SD en nuestro medio, se mencionan los resultados arciales del estudio de prevalencia de enfermedades genéticas en el Instituto de Genética (IG), obtenidos de expedientes de los pacientes correspondientes al periodo de enero de 1998 a dicembre de 2001, con cariotipo compatible con SD, periodo durante el cual se atenderon 89 casos de SD. la edad de derivación para el diagnóstico citogenético se realizó antes de primer año de vida en un75 por ciento. El número de casos fue similar para ambos sexos, el 85.9 porciento de los casos corresponden ala ciudad de La Paz y el 58 porciento de los casos corresponden a madres mayores de 34 años. el porcentaje de presentación de las características fenotípicas es variable en el SD. La alteracion cromosómica más frecuente es a trisomía libre (96,6 porciento). Los datos nacionales permitieron argumentar el proqué se debe realziar el diagnóstico precoz, la importancia del manejo integral y multidisciplinario de los pacientes con SD, la obligación ético moral que tiene el profesional médico de brindar la posibilidad de asesoramiento genético a los padres, familias y el establecer el seguimiento adecuado del paciente. Conclusiones y Recmendaicones: Para realziar el diagnóstico adecuado del Sd y su posterior manejo es imprescindible el estudio citogenético precoz. el manejo inadecuado y e tardío o inexistente diagnóstico citogenético dsminuye las oportunidades de pacientes con sociedad coadyuvando a una mejora calidad de vida del individuo y la familia.

Hallazgo citogenético y molecular de un caso de hermafroditismo verdadero / Citogenético and molecular finding of a case of true hermafroditismo

el hermafroditismo verdadero es una condición poco frecuente, en la cual en un mismo individuo coexisten tejido ovárico y testicular. La mayoría de estos individuos presentan un cariotipo normal y alrededor de un 20 por ciento de los hermafroditas verdaderos muestran un cariotiSe valoró un individuo aparentemente de sexo masculino, con cromatina sexual positiva que presentaba genitales externos ambiguos. Sin embargo, la biopsia gonadal por laparotomía mostró tejido ovárico inmaduro; la ecografía pélvica, ovarios sin folículos y un canal hipoecoico que podría corresponder a la vagina; aún más, la cistouretrografía evidenció una vagina elongada y amplia que finalizaba en una cavidad similar a la uterina. Los hallazgos clínicos y paraclínicos condujeron a realizar el estudio citogenético mediante cariotipo y análisis de secuencias microsatélites strs para tratar de esclarecer el posible mecanismo implicado en este caso en particularpo en mosaico 46 xx 46 xy conocido como quimerismo

Estudio del paciente con genitales ambiguos / Patients with ambiguous genitalia

El estudio de un paciente con genitales ambiguos, requiere por lo menos 3 etapas de estudio. En la primera se deben identificar las alteraciones genitales, los antecedentes gestacionales y heredofamiliares, realizar un cariotipo en sangre periférica o en fibroblastos, determinar los niveles séricos de 17-OH progesterona y testosterona y realizar un ultrasonido abdominal y pélvico. En la segunda etapa se realizan pruebas de estimulación para demostrar la función gonadal y se determinan acciones enzimáticas y características de receptores hormonales. En ocasiones es necesario realizar una laparoscopia o una laparotomía. La tercera etapa requiere la identificación de los genes y hormonas involucrados en el proceso de diferenciación sexual

Duplo y: ¿estigmatización genética? / Duplex y: genetic stigmatization?

La estigmatización genética constituye un hecho que cobra fuerza con los avances de la biología molecular, y el descubrimiento de cada nuevo gen, que aportan las investigaciones del proyecto Genoma Humano, pero existen síndromes como el XYY, que desde su primera descripción se asocian a las formas de conducta de violencia. En el presente trabajo, realizamos una valoración de las principales ideas que acerca de este síndrome y su relación con la criminalidad, aparecen en los reportes hallados en la base de información MEDLINE, en el período de 1990 a mayo de 1998; donde se destacan la insuficiencia de datos personales de los sujetos descritos; éstos son de vital importancia para poder apreciar el papel que el medio social (ambiente) desempeña en la aparición de este fenotipo. Realizamos además, nuestra valoración sobre la ubicación de esta línea problémica entre lo biológico y lo social, así como algunas sugerencias y/o consideraciones; teniendo en cuenta los ilimitados campos, sobre todo desde el punto de vista ético que tiene el síndrome XYY

Fenótipo Rett em paciente com cariótipo XXY: relato de caso / Rett syndrome phenotype in XXY karyotype: case report

Relatamos o caso de um menino com cariótipo XXY que apresenta desordem neurológica progressiva com início por volta dos 11 meses de idade, com estagnaçao do desenvolvimento seguida de regressao. A criança apresenta, ainda, movimentos estereotipados de maos, apraxia manual e microcefalia. Investigaçoes nao constataram presença de qualquer condiçao neurológica ou sistêmica definida que pudesse ser apontada como possível etiologia para o quadro descrito. Trata-se de menino com alteraçoes fenotípicas muito similares àquelas consideradas típicas para a síndrome de Rett que, associadas com a alteraçao cromossômica constatada (cariótipo XXY), constituem quadro de evidente interesse científico.