Genetic analysis of a family with 6q22 microdeletion and 10p15.3p13 microduplication in two consecutive pregnancies / 中华检验医学杂志

Objective:Cytogenetic and molecular genetic analysis was performed on two consecutive antenatal abnormal fetuses and their parents in a family to clarify the copy number variation(CNV) and its mechanism.Methods:The karyotypes of two fetuses and their parents were analyzed by conventional karyotyping techniques, and CNVs of two fetuses and their mother were analyzed by low-coverage whole-genome copy number variation sequencing (CNV-seq) techniques.Results:The amniotic fluid karyotype results of fetus 1 and 2 were 46, XN, der(4)t(4;10)(q35;p13). The mother′s peripheral blood karyotype result was 46, XX, t(4;10)(q35;p13), and the father′s karyotype was normal. The CNV-seq results of fetus 1 and 2 were seq[hg19]6q22.31(122740000-125440000)X1; 10p15.3p13(120000-17260000)X3, suggesting that there was a heterozygous deletion of about 2 700 000 bp in fetal 6q22.31 and a duplication of about 17 140 000 bp in fetal 10p15.3p13. The CNV-seq result of their mother was seq[hg19]6q22.31(122740000-125440000)X1, suggesting that there was a heterozygous deletion of about 2 700 000 bp in 6q22.31. The pregnant woman and her family chose to terminate the pregnancy after genetic consulting.Conclusion:The combined application of karyotyping and CNV-Seq is significantly beneficial to detecting microdeletions or microduplications of fetal chromosomes and effectively preventing the birth of defective children.

Clinical Characteristics and Prognosis of Acute Myeloid Leukemia Patients with inv(16)/t(16;16)(p13.1;q22) and/or CBFβ-MYH11 / 中国实验血液学杂志

OBJECTIVE@#To summarize the clinical and laboratory characteristics of patients with acute myeloid leukemia (AML) with inv(16)/t(16;16) (p13.1;q22), and to analyze the risk factors affecting the prognosis of the patients.@*METHODS@#AML patients with inv(16)/t(16;16) (p13.1;q22) and/or CBFβ-MYH11+ admitted to the Department of Hematology, The First Affiliated Hospital of Soochow University from January 1, 2008 to October 30, 2019 were retrospective analyzed, the clinical and laboratory indicators, as well as treatment plans and efficacy evaluations of the patients were all recorded. Furthermore, related factors affecting the overall survival (OS) and event-free survival (EFS) of the patients were analyzed.@*RESULTS@#Among 151 AML patients with inv(16)/t(16;16) (p13.1;q22) and/or CBFβ-MYH11+, the percentage of additional chromosomal abnormalities was about 27.8%, and the most common additional chromosomal abnormality was +22 (33/151, 21.8%), followed by +8 (11/151, 7.3%). There were 112 patients with perfect NGS examination, and the result showed the most common accompanying gene mutations were KIT mutation (34/112, 30.4%) and FLT3 mutation (23/112, 20.5%). Univariate analysis showed that factors affecting EFS included: NE≤0.5×109/L (P=0.006) and combined K-RAS mutation (P=0.002); Factors affecting OS included: Age≥50 years old (P<0.001) and NE≤0.5×109/L (P=0.016). Multivariate analysis showed that NE≤0.5×109/L (P=0.019) was the risk factors affecting OS. The proportion of bone marrow eosinophilia (BME)≥10.00% (P=0.029) was the risk factors affecting EFS.@*CONCLUSION@#The prognosis for those newly diagnosed AML patients who were of advanced age, the high proportion of bone marrow eosinophils, K-RAS mutations, and agranulocytosis is poor. The treatment plans can be adjusted in the early stage to improve the prognosis of such patients.

Rare type I CBFβ/MYH11 fusion transcript in primary acute myeloid leukemia with inv(16)(p13.1q22): a case report

Inv(16)(p13.1q22) in acute myeloid leukemia (AML) is a common chromosomal abnormality. It leads to the core-binding factor ß-subunit (CBFβ)/smooth muscle myosin heavy chain 11 (MYH11) fusion gene. Different breakpoints were observed in the CBFβ gene at 16q22 and the MYH11 gene at 16p13.1. For this reason, different CBFβ/MYH11 fusion genes are generated, with more than 13 types having been reported to date. Type I CBFβ/MYH11 fusion transcripts are very rare, with only 10 cases being reported to date. This case report describes a primary AML patient with inv(16)(p13.1q22) and a rare type I CBFβ/MYH11 fusion gene. The morphological analysis did not conform to the typical M4eo. Abnormal eosinophils were less than 5%, and there was obvious dysgranulopoiesis. The patient was in hematological and genetic remission for 487 days after the initial chemotherapy cycles. However, the CBFβ/MYH11 fusion had been constantly positive. Moreover, the presence of non-type A fusions may affect its biology and clinical prognosis. Therefore, further studies on understanding its biological and prognostic significance are essential.

Clinical significance of CD34 / 医学前沿

t(8;21)(q22;q22) acute myeloid leukemia (AML) is a highly heterogeneous hematological malignancy with a high relapse rate in China. Two leukemic myeloblast populations (CD34

Queda em idosos: tradução, adaptação transcultural e validação do teste de rastreio Q22-p / Falls in the elderly: translation, transcultural adaptation and validation of the test Q22-p

Traduzir, adaptar transculturalmente para o Brasil e analisar as propriedades psicométricas da versão brasileira do "Teste de rastreio do risco de queda no idoso" (Simple screening test for risk of falls in the elderly - "Q22").Métodos: Realizada a tradução e adaptação transcultural do "Q22". Selecionados idosos da comunidade, 60 anos ou mais, e apurados dados sociodemográficos, uso de medicações e queda no ultimo ano. Aplicada a versão brasileira do instrumento; Q22-p, visando a sua validação e análise de suas propriedades de medidas. Dois entrevistadores o aplicaram num mesmo dia e, após 15 dias, realizada nova aplicação por um dos entrevistadores. O TUGT e FRT também foram obtidos.Resultado: Amostra composta por 51 indivíduos, idade média 74,5 anos, principalmente mulheres, brancas, casadas e com baixa escolaridade. A frequência de queda no último ano foi 33%. Obteve-se uma ótima confiabilidade do Q22-p no Teste ANOVA de medidas repetidas (p=0,938) e no Índice de Correlação Intraclasses (96%; p<0.001). Na validação, apuradas correlações significativas do Q22-p com o TUGT e o FRT, segundo o Coeficiente de Correlação de Pearson, sendo regulares as correlações em ambos os testes, respectivamente, 38,2% (regular/baixa; p<0,001) e 55,1% (p=0,006). Obteve-se a curva ROC para o Q22-p e o escore 6,5 foi visto como o melhor ponto de corte no diagnóstico do risco de queda no idoso...

Prenatal diagnosis of a 7q21.13q22.1 deletion detected using high-resolution microarray

We report a case of de novo 7q interstitial deletion detected by conventional karyotyping and by microarray of amniotic fluid sampled during the prenatal period. A 32-year-old pregnant woman was evaluated at our hospital following detection of increased nuchal translucency at 12 weeks and 5 days of gestation. Conventional karyotyping revealed 46,XX,del(7)(q21q22) in 20 interphase mitotic cells, and high-resolution microarray revealed 12.8 Mb (90,625,014-103,430,901) deletion in the region 7q21.13q22.1. Both parents had normal karyotypes. After birth, the neonate displayed several anomalies, including palatine cleft, upslanted and wide palpebral fissure, low-set ears, micrognathia, microcephaly, ventriculomegaly, subglottic tracheal stenosis, hearing loss, and hand/foot deformities, including brachydactyly, polydactyly, and cutaneous syndactyly. This case study helps explain the phenotype-genotype relationship in patients with 7q21.13q22.1 deletion.

Overgrowth Syndrome with 9q22.3 Microdeletion Detected by Microarray Comparative Genomic Hybridization

Microdeletion of 9q22.3 is a rare chromosomal disorder characterized by body overgrowth, facial dysmorphic features and psychomotor delay. The presence of genomic microdeletion or microdu-plication can not be identified by the conventional chromosomal analysis. Microarray comparative genomic hybridization (CGH) is a newly developed molecular cytogenetic technique that enables the identification of minute copy number variation (CNV) in the human genome. Here, we report a case of microdeletion in the 9q22.31-q22.33 region, which included a patched homolog 1 (PTCH1) gene, as detected by CGH and confirmed by fluorescence in situ hybridization (FISH) analyses in a neonate with prenatal onset of macrosomia, dysmorphism, and muscle hypotonia. To the best of our knowledge, this is the first case report of 9q22.3 microdeletion detected by CGH in Korea.

A Case of Masked t(8;21) in Acute Myeloid Leukemia with Cytogenetic Abnormality of 45,X,-Y,t(8;17)(q22;p13)

The t(8;21)(q22;q22) is one of the most frequent structural chromosomal anomaly found in AML, occurring in about 5% of all AML and in 10% of AML with maturation (M2). And approximately 3.4% of AML with t(8;21)(q22;q22) occurs as a complex chromosomal abnormality and occasionally shows discrepancy between cytogenetic and molecular genetic analyses. We report a case of 42 yr old male patient that revealed morphological characteristics of AML-M2 and karyotypic abnormality of 45,X,-Y,t(8;17)(q22;p13) without visible involvement of chromosome 21 by conventional cytogenetic study with masked t(8;21) identified by FISH using RUNX1/RUNX1T1 probes. FISH confirmed nuc ish (RUNX1T1x3),(RUNX1x3), (RUNX1T1 con RUNX1x1). According to the results of conventional cytogenetic and FISH analyses, the karyotype was revised to 45,X,-Y,t(8;17;21)(q22;p13;q22).

A Case of Partial Trisomy 9q Derived from Paternal Chromosome

There are few cases of partial trisomy of 9q, known as partial 9q trisomy syndrome with low birth weight, microcephaly, hypotelorism, beaked nose, small lip, long finger, hypertrophic pyloric stenosis, ventricular septal defect, and mental retardation. We report partial trisomy of 9q derived from a paternal chromosome, which has different features of other syndromes, including prematurity, atrial and ventricular septal defect, patent ductus arteriosus, persistent left superior vena cava, congenital hydronephrosis, and scrotal hernia

Two Cases of Acute Myeloid Leukemia with t(16;21)(p11;q22) and TLS/FUS-ERG Fusion Transcripts / 대한진단검사의학회지

Many AML-associated chromosomal abnormalities, such as t(8;21), t(15;17), inv(16), t(9;11), t(9;22) and t(6;9) are well known. The chromosomal aberration of t(16;21)(p11;q22) in AML is rare and it is known to be associated with poor prognosis, young age (median age, 22 yr), and involvement of various subtypes of the French-American-British classification. We report here 2 AML patients with t(16;21)(p11;q22), proved by conventional cytogenetics and/or reverse transcription (RT)-PCR. Erythrophagocytosis by leukemic blasts was observed in both of the cases. One patient was a 24 yr-old male with acute myelomonocytic leukemia. His karyotype was 46,XY,t(16;21)(p11;q22),del(18)(p11.2) and RT-PCR revealed the TLS/FUS-ERG fusion transcripts. Although he received allogeneic peripheral blood stem cell transplantation after the first remission, he died 9 months after the initial diagnosis due to relapse of the disease and graft-versus-host disease. The other patient was a 72 yr-old male with acute myeloid leukemia without maturation. His karyotype was 45,XY,-16,add(21)(q22) and the presence of t(16;21)(p11;q22) was detected by RT-PCR. He was transferred to another hospital with no more follow-up. We suggest that the presence of t(16;21)(p11;q22) and/or TLS/FUS-ERG fusion transcripts has to be considered in cases of AML with erythrophagocytosis.

Deleção do cromossomo 9 na região q22q32 em bebê com cariótipo 46XY: relato de um caso / Deletion of chromosome 9 in the region q22q32 in a male baby with karyotype 46XY: report of a case

Este trabalho teve como objetivo o estudo laboratorial e por imagem das malformações de um bebê do sexo masculino que apresentou, por ocasião do parto, prematuridade, cardiopatia congênita, insuficiência respiratória e malformação congênita. O estudo ecográfico gestacional mostrou o osso nasal hipoplásico e a coluna vertebral com pequeno desvio na transição entre a coluna cervical e a torácica. No coração foi constatada a presença de Golf-Ball em ventrículo esquerdo e no trato genitourinário, pielectasia renal bilateral. Os estudos citogenéticos diagnosticaram deleção intersticial do cromossomo 9 do segmento q22q32 no braço longo, onde se estabeleceu o cariótipo 46,XY,del(9)(q22q32).

This study aimed at the laboratory and imaging investigation of malformations in a male baby that presented prematurity, congenital cardiopathy, respiratory failure and congenital malformation at the time of delivery. The gestational ultrasonography showed a hypoplastic nasal bone and a minor spinal deviation at the transition between the cervical and thoracic spine. There was Golf-Ball in the left ventricle and, in the genitourinary tract, bilateral renal pyeloectasis was observed. Cytogenetic studies revealed interstitial deletion of chromosome 9 from the segment q22q32 in the long arm, where the karyotype 46, XY, del (9) (q22q32) was identified.

Acute Myeloid Leukemia with t(8;21)(q22;q22) (AML1/ETO) in a Patient with Marked Hypocellularity and Low Blasts Count / 영남의대학술지

According to the World Health Organization (WHO) classification system, cases with t(8;21)(q22;q22) should be diagnosed as acute myeloid leukemia (AML) even with a blast count of less than 20 percent in blood or bone marrow. It is an uncommon manifestation, moreover hypocellularity is rarely observed in this subtype of leukemia. Here, we report a case of t(8;21) in a patient with marked hypocellularity of less than 5 percent and a blast count of less than 20 percent. This patient responded relatively well to chemotherapy. An allogeneic bone marrow transplantation was performed with good engraftment . This case suggests that hypocellular AML with a t(8;21) has as good a prognosis as hypercellular AML with t(8;21).

A Case of de Novo Interstitial Deletion 16(Q13q22) / 대한주산의학회잡지

Deletion of the long arm of chromosome 16 is uncommon. The causes of deletion are two: one is unbalanced translocation and the other is de novo deletion. In our case, a baby was born with characteristics of the deletion of the long arm of chromosome 16: distinct craniofacial dysmorphism, mild hydrocephalus, ventriculoseptal defect, coarctation of aorta, short neck, low set, small and posterially rotated ears and shortening of long bones. High resolution GTG and RBG banding analyses revealed a karyotype: 46, XY, del(16)(q13q22) de novo.

Two Cases of Erythroleukemic Blast Crisis in Chronic Myelogenous Leukemia / 대한임상병리학회지

The erythroleukemic blast crisis in chronic myelogenous leukemia (CML) is rarely reported. We present two cases of erythroleukemic blast crisis of CML. In both cases, they had been treated with interferon and hydroxyurea prior to a blast crisis of CML. On blastic transformation, one patient underwent an acute clinical transformation marked with fever and hematochezia but the other showed no clinical deterioration. The blasts appeared in the peripheral blood. The bone marrow aspirates revealed megaloblastic erythroid hyperplasia (about 72%, 54% of all nucleated cells), increasing the number of myeloblasts (about 46%, 59% of all non-erythroid cells), and erythroblasts with a positive PAS stain. The cytogenetic studies revealed Philadelphia chromosomes with additional chromosomal abnormalities, t(3;21)(q26;q22) and the FISH studies revealed bcr-abl fusion signals in bone marrow cells. One case expired 8 months later despite of hydroxyuria therapy. The other case received allogeneic bone marrow transplantation (alloBMT) without complete remission but expired 34 weeks after alloBMT due to GVHD.

A Case of Hypoglossia-Hypodactylia with t(3q;19p)

Hypoglossia-hypodactylia syndrome is a congenital disease which is characterized by severe micrognathia, hypoglossia and various anomalies of extremities. This was first reported as 'aglossia congenita' back in 1932 by Rosenthal, and has been reported many times ever since, but has never been reported in Korea. Hall first used the term 'hypoglossia-hypodactylia syndrome', and classified it as one of the oromandibular-limb hypogenesis syndromes. According to the studies, most of the cases are sporadic, and this is known to be due to the dominant mutant gene. Etiology is still unknown, but a number of theories have been proposed, such as intrauterine damage and vascular distruptive mechanism. We report a case on hypoglossia-hypodactylia syndrome in a male neonate with karyotype showing 46,XY,t(3;19)(q22;p12) with the review of the associated literatures.