Variantes citogenéticas en pacientes con síndrome de Turner diagnosticadas en un hospital de tercer nivel de atención en Ecuador / Cytogenetic variants in patients with Turner syndrome diagnosed in a third level care hospital in Ecuador

Resumen Introducción: El Síndrome de Turner (ST) es una alteración cromosómica sexual causada por la ausencia parcial o completa del cromosoma X, además de mosaicismos y otras alteraciones estructurales del cromosoma X o Y; está presente en 1 de 2500 nacidas vivas. Objetivo: Describir las variantes citogenéticas de pacientes con síndrome de Turner y evaluar su asociación con el fenotipo de presentación y la edad del diagnóstico. Método: Estudio retrospectivo de corte transversal de una serie de 82 casos de síndrome de Turner. Los cariotipos fueron realizados utilizando el medio RPMI-1640; las preparaciones de cromosomas se obtuvieron utilizando técnicas estándar y se analizaron mediante bandas GTG con una resolución de 400-450 bandas, donde se contó con 20-50 metafases para reducir la probabilidad de no detección de mosaicismo. Resultados: 45 (55.6%) fueron diagnosticadas, con monosomía clásica del cromosoma X, mientras 29 (35,8%) mostraron anomalías estructurales del cromosoma X y 7 (8,6%) se asociaron a mosaicos numéricos del cromosoma X. Solo 21 (26%) pacientes fueron diagnosticadas por debajo de los 12 años, mientras el resto 60 (74%) se detectaron entre la adolescencia y la adultez. La baja estatura fue una característica universal en todos los grupos de estudio. Conclusiones: Las fórmulas cromosómicas en el síndrome de Turner pueden ser muy variadas y tener diversas implicaciones en el fenotipo; se destaca la baja talla como un criterio clínico relevante en la sospecha clínica.

Abstract Introduction: Turner Syndrome (TS) is a sexual chromosomal alteration caused by the partial or complete absence of the X chromosome, in addition to mosaicisms and other structural alterations of the X or Y chromosome; It is present in 1 in 2,500 live births. Objective: To describe the cytogenetic variants of Turner syndrome patients and to evaluate their association with the phenotype at presentation and age at diagnosis. Methods: Retrospective cross-sectional study of a series of 82 cases of Turner syndrome. Karyotypes were performed using RPMI-1640 medium; Chromosome preparations were obtained using standard techniques and analyzed by GTG banding with a resolution of 400-450 bands where 20-50 metaphases were counted to reduce the probability of missing mosaicism. Results: 45 (55.6%) were diagnosed with classic monosomy of the X chromosome, while 29 (35.8%) showed structural abnormalities of the X chromosome and 7 (8.6%) were associated with numerical mosaics of the X chromosome. Only 21 (26%) patients were diagnosed under 12 years of age, while the rest 60 (74%) were detected between adolescence and adulthood. Short stature was a universal characteristic in all study groups. Conclusions: The chromosomal formulas in Turner syndrome can be variable and have different implications in the phenotype; short stature stands out as a relevant clinical criterion in clinical suspicion.

Genetic analysis of a case with Pierre-Robin sequence due to partial 1q trisomy and partial 4q monosomy / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a neonate with Pierre-Robin sequence.@*METHODS@#The child was subjected to chromosomal karyotyping, single nucleotide polymorphism array (SNP-array)-based comparative genomic hybridization and fluorescence in situ hybridization (FISH) analysis.@*RESULTS@#The child has featured microgthnia, glossoptosis, upper airway obstruction, mandible dehiscence and short neck. He was found to have a karyotype of 46,XY,der(4)add(4)(q34). Her mother's karyotype was determined as 46,XX,t(1;4)(q43;q34), while his father was 46,XY. SNP-array analysis suggested the child to be arr [hg19] 1q42.2q44 (232 527 958-249 202 755)× 3; 4q34.3q35.2 (168 236 901-190 880 409)× 1. The result of SNP-array for both parents was normal. FISH analysis confirmed that his mother has carried a balanced t(1;4)(q42;34) translocation. The aberrant chromosome 4 in the child has derived from his mother's translocation, which gave rise to partial 1q trisomy and 4q monosomy.@*CONCLUSION@#The 1q42.2q44 duplication and 4q34.3q35.2 deletion of the child probably underlay his abnormal phenotype of Pierre-Robin sequence.

Clinical characterization and genetic analysis of a newborn with chromosome 8q21.11 deletion syndrome / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic etiology for a newborn with corneal opacity.@*METHODS@#The neonate and her parents were subjected to routine G-banding chromosomal karyotyping analysis. Copy number variation (CNV) was analyzed with low-coverage whole-genome sequencing (WGS) and single nucleotide polymorphism microarray (SNP array).@*RESULTS@#No karyotypic abnormality was found in the newborn and her parents. Low-coverage WGS has identified a de novo 5.5 Mb microdeletion at chromosome 8q21.11-q21.13 in the neonate, which encompassed the ZFHX4 and PEX2 genes. The result was confirmed by SNP array-based CNV analysis.@*CONCLUSION@#The newborn was diagnosed with chromosome 8q21.11 deletion syndrome. ZFHX4 may be one of the key genes underlying this syndrome.

Analysis of a pedigree with partial trisomy 9 and partial monosomy 13 derived from a maternal balanced t(9;13) translocation / 中华医学遗传学杂志

OBJECTIVE@#To determine the nature and origin of aberrant chromosomes in a child with multiple anomalies and psychomotor retardation.@*METHODS@#Routine G-banding was carried out to analyze the karyotypes of the patient and his parents, and next generation sequencing for copy number variations (CNV-seq) was used for the fine mapping of the aberrant chromosomal regions.@*RESULTS@#The proband and his uncle exhibited psychomotor retardation, craniofacial malformation, infantile external genitalia, and concealed penis. Cytogenetic analysis indicated that the child has a 46,XYqh+,+(9),t(9;13)(q13;q12),pat,-13 karyotype. His uncle was XYqh+,+(9),t(9;13)(q13;q12)mat,-13, his father was 46,XYqh+,t(9;13)(q13;q12)mat, his grandmother was 46,XX,t(9;13)(q13;q12), and his grandfather was 46,XYqh+. The result of CNV-seq assay for the child was 46,XY,+9p(pter-p13.2,-40 Mb×3). No deletion was detected.@*CONCLUSION@#The partial trisomy 9 and partial monosomy 13 probably underlie the phenotypic abnormalities in the child. Combined chromosomal karyotyping and DNA sequencing can facilitate delineation of the nature and origin of the aberrant chromosomes.

Genotypic and phenotypic analysis of a patient with de novo partial monosomy 18p and partial trisomy 18q / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic cause for a patient with intellectual disability, short stature and multiple congenital anomalies, and to correlate the result with the clinical phenotype.@*METHODS@#Routine karyotyping analysis was carried out on GTG-banded metaphase chromosomes. Single nucleotide polymorphism (SNP) microarray was used to detect microdeletions or microduplications in the patient. Fluorescence in situ hybridization (FISH) was used to ascertain the origin of aberrant chromosomes.@*RESULTS@#The karyotype of the patient was 46,XY,der(18), while both of his parents had a normal karyotype. SNP array identified a 1.23 Mb deletion at 18p11.32-pter (chr18: 136 227-1 370 501, hg19) and a 33.76 Mb duplication at 18q21.1-qter (chr18: 44 250 359-78 013 728, hg19) in the patient. Above finding was confirmed by dual-color FISH with one color for 18p and another for 18q. The patient presented with some common features of 18p deletion and 18q duplication including intellectual disability and growth retardation, in addition with some features of 18p deletion including pectus excavatum, short stature and growth hormone (GH) deficiency. The patient showed progressive improvement of stature with GH therapy. Comparison of patients with previously reported dup(18q)+del(18p) recombinations suggested that, even for patients with similar breakpoints, their phenotypes have ranged from normal to severe and there were no consistent findings.@*CONCLUSION@#As aberrations involving double chromosomal segments often result in phenotypic variability, it has been difficult to correlate the genotype of our patient with his phenotype.

Clinical Significance of Monosomal Karyotype in MDS / 中国实验血液学杂志

OBJECTIVE@#To investigate the frequency, karyotype characteristics and prognosis significance of monosomal karyotype (MK) in newly diagnosed MDS patients.@*METHODS@#The clinical, laboratorial and follow-up data of 202 MDS patients received the chromosome karyotype test in Department of Hematology, Ningbo Hospital of Zhejiang University from 2009 to 2018 were analyzed retrospectively, the monosomal karyotype features, clinical characteristics and their effects on the prognosis of MDS patients also were analyzed.@*RESULTS@#Among 202 cases of MDS, 25 (12.38%) confirmed to be the MK. The abnormality of chromosome 5 (60.00%), 7 (56.00%), 17 (56.00%), 15 (56.00%), 13 (40.00%) and 20（40.00%）were common in monosomal karyotype. MK-MDS (MDS with monosomal karyotype) patients had higher bone marrow blast percentage than MK-MDS (MDS without monosomal karyotype) patients, the median are 6.25% and 3.00% (P＜0.01) respectively, but there were no difference in age, sex, hemoglobin level, white blood cell count, neutrophile granulocyte percentage, platelet count, blood blast percentage, serum ferritin, folic acid and vitaminB12 between MK-MDS and MK-MDS. The overall survival time of MK-MDS and MK-MDS patiens with chromosome 3, 5, 7, 13, 15, 17 abnormalities was significantly shorter than MK-MDS and AK+MK-MDS patients (MDS with abnormal karyotype but without monosomal karyotype) , the MK-MDS patients had a median survival time of 7.33 months, but the median survival time had not been reached in MK-MDS and AK+MK-MDS patients had not been reached by the end of the follow-up, and could not be assessed (P＜0.01).@*CONCLUSION@#The monosomal karyotype is a poor prognosis factor for newly-diagnosed MDS patients. The poor prognosis suggested by monosomal karyotype may be related with the abnormality of 3, 5, 7, 13, 15 and 17 chromosome.

Dental Management in a Patient with Turner Syndrome with Dental Anomalies: A Case Report / 대한소아치과학회지

Turner syndrome (TS) is a chromosomal disorder caused by monosomy of the X chromosome, with complete or partial absence of the second sex chromosome. Anomalies of root morphology have been found to occur more often in patients with TS, which make endodontic treatment challenging and requires special handling. The patients with TS may also have systematic problems such as cardiac or renal malformations, so in treating these patients it is important for clinicians not only to be aware of the characteristic intraoral findings, but also to make the patients have regular dental check-ups to prevent oral complications in advance.An 12-year-old girl who had been diagnosed with TS at the age of 10 years was referred due to discomfort in the bilateral mandibular premolar regions. Dens evaginatus and taurodontism were detected in all the mandibular premolars characteristically. The bilateral mandibular first premolars had three roots and the bilateral mandibular second premolars had periapical lesion with two roots. Due to the complexity of the root canal anatomy, root canal treatment were completed with a dental microscope to ensure adequate visualization. After 2 years of regular follow-up examinations, there were no clinical sign or symptom associated with the teeth, and no periapical lesion, was found.This case report describes the characteristic oral features and dental management of TS patients.

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.

Diabetes insipidus como manifestação inicial de leucemia mieloide aguda em paciente com monossomia do cromossomo 7 / Diabetes insipidus as initial manifestation of acute myeloid leukemia in a patient with monosomy of chromosome 7

O diabetes insipidus (DI) central é uma síndrome caracterizada pela incapacidade de concentração urinária devido à deficiência do hormônio antidiurético. O envolvimento do sistema nervoso central é frequente nas leucemias, mas a ocorrência de DI é rara e confere pior prognóstico. A patogênese do DI na leucemia não é totalmente conhecida, mas a infiltração do eixo hipotálamo-hipofisário por células leucêmicas parece ser um fator responsável. O presente relato descreve o caso de um paciente que apresentou DI como primeira manifestação de leucemia mieloide aguda e que evoluiu com dificuldades de ajustes do sódio sérico, da poliúria e da reposição volêmica, necessitando de permanência prolongada em unidade de cuidados intensivos(AU)

Central diabetes insipidus (DI) is a syndrome characterized by the inability to concentrate urine due to a lack of antidiuretic hormone. Involvement of the central nervous system is common in acute leukemia, but the occurrence of DI is rare and determines a worse prognosis. The pathogenesis of DI in leukemia has not been fully understood yet, but infiltration of the hypothalamic-pituitary axis by leukemic cells seems to be involved. This report describes a case of a patient who presented with DI as the first manifestation of acute myeloid leukemia. Difficulties in the management of serum sodium, fluid replacement and polyuria led to prolonged length of stay in an intensive care unit(AU)

Two false negative cases in noninvasive prenatal testing for fetal chromosomal aneuploidies / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the limitation of non-invasive prenatal testing (NIPT) technique through analyzing two false negative cases.</p><p><b>METHODS</b>Chromosomal karyotyping analysis was performed on umbilical cord blood sample derived from case 1 at 24 weeks' gestation and peripheral blood sample derived from the neonate of case 2. Placental tissues of case 1 and peripheral blood sample of case 2 were also analyzed by high-throughput sequencing for copy number variations (CNVs).</p><p><b>RESULTS</b>For case 1, analysis of fetal umbilical cord blood sample showed a translocation type of trisomy 21, i.e., 46,XY,der(21;21)(q10;q10),+21. There were no obvious abnormalities detected at or near the center of the fetal surface and matrix surface of the placenta. High-thoroughput sequencing showed Chr13:(33 840 001 - 115 100 000)×3[60%]/46,XY[40%] at the edge of the placenta, Chr13:(34 080 001-115100000)×3[54%]/46,XY[46%] at the edge of placenta matrix surface, and trisomy 21 in the umbilical cord tissue. For case 2, analysis of the neonatal peripheral blood sample showed a karyotype of 46,XY,del(18)(q22), which revealed a microdeletion in chromosome 18. High-throughput sequencing of the maternal peripheral blood sample stored during pregnancy confirmed it to be chr18: (62 910 000 - 78 020 000)×1 with 15.1 Mb deletion in the fetus. The neonate was therefore diagnosed with partial monosomy of chromosome 18.</p><p><b>CONCLUSION</b>False negative results of NIPT are related with the fraction of circulating cell-free fetal DNA in the maternal serum. NIPT has limitations in detecting fetal chromosomal microdeletion and confined placenta mosaicisms. Routine ultrasound scan is necessary for pregnant women with low-risk indicated by NIPT.</p>

Cytogenetic and molecular characterization of a patient with partial 6q trisomy and 1q monosomy / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze a girl with moderate mental retardation and speech and language disorders with cytogenetics technique and next-generation sequencing (NGS).</p><p><b>METHODS</b>G-banding chromosome analysis was used to ascertain the karyotype of the child and her parents, and NGS was used for determining the size and origin of the abnormal chromosome fragment. Mate-pair and PCR were used to determine its parental origin.</p><p><b>RESULTS</b>The karyotype of the child was determined to be 46,XX,add(1)(q44)dn, while her parents were both normal. NGS revealed that the child has harbored a partial trisomy of 6q24.3-q27, and the breakpoint was mapped to at 6q24.3q27. In addition, a 2.5 Mb microdeletion at 1q44 was found in the patient.</p><p><b>CONCLUSION</b>No recognizable phenotype was associated with 1q44 deletion. The abnormal phenotypes presented by the child may be attributed to the 6q24.3-q27 triplication. Compared with conventional cytogenetic analysis, NGS has a much higher resolution and great accuracy.</p>

Trastornos neurológicos graves y malformaciones en una niña con monosomía del cromosoma 21 / Severe neurological disorders and malformations in a girl with mo- nosomía of the chromosome 21

Se presenta el caso de una niña de 7 años de edad, que fue remitida a la Consulta de Asesoramiento Genético, por presentar malformaciones congénitas severas y rasgos dismórficos, asociado a un retardo del neurodesarrollo. Al nacer se diagnosticó una comunicación interauricular, lo cual fue corregido mediante operación cardiaca. Se le realizó estudio por técnicas de citogenética convencional obteniéndose como resultado una monosomía del cromosoma 21. El estudio de citogenética molecular por técnica FISH detectó una inserción de la zona crítica del 21 en la región subtelomérica del 6p.

The case of a 7-year-old girl is showed. She was referral to the Genetic Advice Session, for presenting severe congenital malformations and dysmorphisms, associated with a neurological delay. A canal inter auricle was diagnosed at birth, which was corrected through heart surgery. The conventional cytogenetic analyzed showed a 21 chromosome monosomy. The study of molecular cytogenetic detected an insertion of the critical region of 21 in the subteloméric 6p region.

Prognostic significance of monosomal karyotype in acute myeloid leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the prognostic significance of monosomal karyotype (MK) in patients with acute myeloid leukemia (AML).</p><p><b>METHODS</b>The clinical data of 498 AML patients were analyzed retrospectively.</p><p><b>RESULTS</b>Of the 498 patients, 233 (46.8%) cases had an abnormal karyotype. 42 patients fulfilled the criteria for MK, which were 8.4% of all cases and 18.0% of patients with abnormal karyotype, respectively. The most frequent autosomal monosomies were -7 and -17. 70 patients had complex karyotype (CK), in all patients and patients with abnormal karyotype accounted for 14.1% and 30.0%, respectively. Patients with MK were associated with significantly older (median age 62.5 vs 52 years, P=0.003), and lower HGB concentrations (62.5 vs 77 g/L, P=0.009) and lower WBC counts (7.0×10⁹/L vs 11.7×10⁹/L, P=0.008). Among MK cases, the most frequent chromosome abnormalities were complex karyotype, -7, -5, 7q-, and 5q-. In univariate analysis, MK patients had worse survival than those without MK (7.3 months vs 26.3 months, P<0.001). CK patients also had poorer outcomes than patients without CK (14.8 months vs 26.3 months, P<0.001). In CK patients, survival was worse in MK patients than patients without MK (7.4 months vs 19.2 months, P=0.007). By COX analysis, MK was an independent prognostic factor, beyond NCCN criteria and CK [HR=2.610 (1.632-4.175), P<0.001].</p><p><b>CONCLUSION</b>MK was an independent adverse prognostic factor in AML patients.</p>

Mixed gonadal dysgenesis in 45,X Turner syndrome with SRY gene

Turner syndrome is the most common chromosomal disorder in girls. Various phenotypic features show depending upon karyotype from normal female through ambiguous genitalia to male. Usually, Turner girls containing 45,X/46,XY mosaicism, or sex-determining region Y (SRY) gene may have mixed gonadal dysgenesis with various external sexual differentiation. We experienced a short statured 45,X Turner girl with normal external genitalia. Because SRY gene was positive, laparoscopic gonadectomy was performed. The dysgenetic gonads revealed bilateral ovotesticular tissues. The authors report a mixed gonadal dysgenesis case found in clinical 45,X Turner patient with positive SRY gene. Screening for SRY gene should be done even the karyotype is 45,X monosomy and external genitalia is normal.

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.

Monosomal karyotype among adult acute myeloid leukemia: clinical characteristic and prognostic analysis / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the clinical characteristics and prognostic value of monosomal karyotype (MK) patients in adult acute myeloid leukemia (AML).</p><p><b>METHODS</b>We retrospectively studied 45 patients of MK⁺ in newly-diagnosed adult AML in our center from Oct 2000 to Dec 2012. Clinical characteristics, cytogenetic data and prognostic features were analyzed in the cohort of MK⁺ patients.</p><p><b>RESULTS</b>MK was found in 45 patients (19.0%) of 237 newly-diagnosed adult AML with cytogenetic data available at diagnoses. Among these 45 cases, there were 28 male (62.2%) and 17 female (37.8%). Median age of MK⁺ patients at diagnose was 58(18-91) years old. The presence of -5(31.1%) and -7(17.8%) were the most common chromatid among MK⁺ AML patients. MK was much more prevalent among elderly patients. Among AML patients, the proportions of MK⁺ patients younger than 30, 30 to 59 and older than 60 years old groups were 11.5%, 17.7% and 22.4%, respectively. There was no difference between MK⁺ and MK⁻ patients in gender distribution (P=0.545). There was also no difference between MK⁺ and MK⁻ patients in the distribution of FAB castigation (P=0.239). Median survival of MK⁺ AML patients was 6.5 months. Cumulative 5-year overall survival (OS) of was 5.2%. Forty-three MK⁺ patients (43/45, 95.6%) also had a complex karyotype (CK). Two cases that did not meet the CK had not achieved complete remission (CR), and died within 6 months. There were 12 patients who were CK⁺ in 192 MK⁻ patients. The differences of OS and CR rates between MK⁺CK⁺ patients and MK⁻CK⁺ were statistically significant (P<0.05).</p><p><b>CONCLUSION</b>The increased detection rate of MK with age was associated with lower CR and OS in AML patients.</p>

Clinical and genetics characteristics of patients with monosomal karyotype acute myeloid leukemia patients / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the clinical and genetics characteristics of patients with monosomal karyotype acute myeloid leukemia (MK-AML).</p><p><b>METHODS</b>The karyotypes of 3743 patients with newly-diagnosed de novo AML were analyzed, which had identified 153 cases with MK-AML, for whom the clinical and genetics characteristics were analyzed.</p><p><b>RESULTS</b>There were 2056 patients (54.9%) among all patients. A total of 153 patients fulfilling the criteria for MK-AML were identified, which comprised 93 males and 60 females, with a median age of 54. The median white blood cell count on presentation was 4.4×10 (9)/L. One hundred and forty-five cases (94.8%) have fulfilled the criteria for complex karyotype (≥ 3 chromosomal abnormalities). Although the monosomy could be found with all autosomes, chromosome 7 has been most frequently involved (38.56%, 59/153).</p><p><b>CONCLUSION</b>MK-AML is a distinct cytogenetic subtype of AML. Monosomy 7 is frequently detected among MK-AML patients. The monosomal karyotype is common among elder patients with AML.</p>

Monosomal and complex karyotypes as prognostic parameters in patients with International Prognostic Scoring System higher risk myelodysplastic syndrome treated with azacitidine

BACKGROUND: Azacitidine (AZA) is standard care for patients with myelodysplastic syndrome (MDS) who have not had allogeneic stem cell transplantation. Chromosomal abnormalities (CA) including complex karyotype (CK) or monosomal karyotype (MK) are associated with clinical outcome in patients with MDS. METHODS: We investigated which prognostic factors including CAs would predict clinical outcomes in patients with International Prognostic Scoring System (IPSS) higher risk MDS treated with AZA, retrospectively. CK was defined as the presence of three or more numerical or structural CAs. MK was defined as the presence of two or more distinct autosomal monosomies or single autosomal monosomy with at least one additional structural CA. RESULTS: A total of 243 patients who treated with AZA, were enrolled. CK was present in 124 patients and MK was present in 90 patients. Bone marrow blasts > or =15% and CK were associated with poorer response (P=0.038, P=0.007) and overall survival (OS) (P3 CAs was associated with poorer OS (group including 3 CAs vs. only three CAs, P=0.001). CONCLUSION: CK was an important prognostic parameter associated with worse outcome. MK may predict poor survival in only non-CK status. The higher number of CAs was associated with poorer survival.

Mosaic Turner syndrome associated with schizophrenia

Turner syndrome is a sex-chromosome disorder; occurring in 1 in 2,500 female births. There are sporadic few case reports of concomitant Turner syndrome with schizophrenia worldwide. Most Turner females had a 45,X monosomy, whereas the majority of comorbidity between Turner syndrome and schizophrenia had a mosaic karyotype (45,X/46,XX). We present a case of a 21-year-old woman with Turner syndrome, mosaic karyotype (45,X/46,XX), showing mental retardation, hypothyroidism, and schizophrenia. HOPA gene within Xq13 is related to mental retardation, hypothyroidism, and schizophrenia. Our case may be a potential clue which supports the hypothesis for involvement of genes on X chromosome in development of schizophrenia. Further studies including comorbid cases reports are need in order to discern the cause of schizophrenia in patients having Turner syndrome.