OBJECTIVE: To delineate a small supernumerary marker chromosome (sSMC) derived from chromosome 9 with combined cytogenetic and molecular methods. METHODS: For a pregnant woman with fetal ultrasound revealing left ventricular punctate hyperechoic echo, and a high risk for monosomy or partial deletion of chromosome 8, chromosome 9 trisomy, monosomy or partial deletion of chromosome 11 by non-invasive prenatal testing, and an abnormal MOM value revealed by mid-term serum screening, amniocentesis was performed for G banded chromosomal analysis and single nucleotide polymorphism array (SNP-array) assay. Peripheral blood samples of the woman and her spouse were also collected for the above tests. In addition, the woman was further subjected to C banding karyotyping analysis and fluorescence in situ hybridization (FISH) assay. RESULTS: The G-banded karyotype of the pregnant women was 47,XX,+mar[20]/46,XX[80], whilst C-banding analysis showed a deep stain in the middle of the sSMC (suggestive of centromeric region) and light stain at both ends (suggestive of euchromatism). FISH combined with DAPI banding analysis using 9pter/9qter probes revealed a karyotype of 47,XX,+mar.ish i(9)(9p10)(9p++)[2]/46,XX[18], whilst SNP-array has revealed a 68.1 Mb duplication in the 9p24.3q13 region. A database search has suggested the duplication to be likely pathogenic. No abnormality was found in her fetus and spouse by karyotyping and SNP-array analysis. CONCLUSION Through combined cytogenetic and molecular genetic analysis, a sSMC derived from chromosome 9 was delineated, which has enabled genetic counseling for the couple.
Female ; Humans ; Pregnancy ; Biomarkers ; Chromosomes, Human, Pair 9/genetics* ; Genetic Testing ; In Situ Hybridization, Fluorescence ; Monosomy

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.
Chromosome Banding ; Chromosomes, Human, Pair 8/genetics* ; DNA Copy Number Variations ; Female ; Genetic Testing ; Homeodomain Proteins/genetics* ; Humans ; Infant, Newborn ; Karyotyping ; Monosomy/genetics* ; Peroxisomal Biogenesis Factor 2/genetics* ; Polymorphism, Single Nucleotide ; Transcription Factors/genetics*

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.
Child ; Comparative Genomic Hybridization ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Infant, Newborn ; Male ; Monosomy ; Pierre Robin Syndrome/genetics* ; Translocation, Genetic ; Trisomy/genetics*

OBJECTIVETo analyze a girl with moderate mental retardation and speech and language disorders with cytogenetics technique and next-generation sequencing (NGS).

METHODSG-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.

RESULTSThe 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.

CONCLUSIONNo 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.

Adult ; Child ; Chromosome Banding ; Chromosome Disorders ; genetics ; Chromosomes, Human, Pair 1 ; genetics ; Chromosomes, Human, Pair 6 ; genetics ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Intellectual Disability ; genetics ; Male ; Monosomy ; genetics ; Trisomy ; genetics

OBJECTIVETo investigate the clinical and genetics characteristics of patients with monosomal karyotype acute myeloid leukemia (MK-AML).

METHODSThe 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.

RESULTSThere 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).

CONCLUSIONMK-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.

Adult ; Aged ; Chromosomes, Human, Pair 7 ; genetics ; Female ; Humans ; Karyotype ; Leukemia, Myeloid, Acute ; genetics ; Male ; Middle Aged ; Monosomy ; Young Adult

OBJECTIVETo explore the clinical characteristics and prognostic value of monosomal karyotype (MK) patients in adult acute myeloid leukemia (AML).

METHODSWe 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.

RESULTSMK 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).

CONCLUSIONThe increased detection rate of MK with age was associated with lower CR and OS in AML patients.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Chromosome Aberrations ; Female ; Humans ; Karyotyping ; Leukemia, Myeloid, Acute ; diagnosis ; genetics ; Male ; Middle Aged ; Monosomy ; Prognosis ; Remission Induction ; Retrospective Studies ; Young Adult

BACKGROUNDMuch is known about the cytogenetic lesions that characterize multiple myeloma (MM) patients from the USA, Europe, and East Asia. However, little has been published about the disease among Southeast Asians. The aim of this study was to determine the chromosomal abnormalities of MM patients in our Singapore population.

METHODSForty-five newly-diagnosed, morphologically confirmed patients comprising 18 males and 27 females, aged 46 - 84 years (median 65 years) were investigated by karyotyping and fluorescence in situ hybridization (FISH). FISH employing standard panel probes and 1p36/1q21 and 6q21/15q22 probes was performed on diagnostic bone marrow samples.

RESULTSThirty-four cases (75.6%) had karyotypic abnormalities. Including FISH, a total detection rate of 91.1% was attained. Numerical and complex structural aberrations were common to both hyperdiploid and non-hyperdiploid patients. Numerical gains of several recurring chromosomes were frequent among hyperdiploid patients while structural rearrangements of several chromosomes including 8q24.1 and 14q32 characterized non-hyperdiploid patients. With FISH, immunoglobulin heavy chain (IGH) gene rearrangements, especially fibroblast growth factor receptor 3 (FGFR3)/IGH and RB1 deletion/monosomy 13 were the most common abnormalities (43.4%). Amplification 1q21 was 10 times more frequent (42.5%) than del(1p36) and del(6q21).

CONCLUSIONSWe have successfully reported the comprehensive cytogenetic profiling of a cohort of newly-diagnosed myeloma patients in our population. This study indicates that the genetic and cytogenetic abnormalities, and their frequencies, in our study group are generally similar to other populations.

Aged ; Aged, 80 and over ; Chromosome Aberrations ; Cytogenetics ; Female ; Humans ; Immunoglobulin Heavy Chains ; In Situ Hybridization, Fluorescence ; Karyotyping ; Male ; Middle Aged ; Monosomy ; genetics ; Multiple Myeloma ; genetics ; pathology ; Receptor, Fibroblast Growth Factor, Type 3 ; genetics ; Retinoblastoma Protein ; genetics ; Singapore

Monosomic karyotype (MK) has recently been associated with poor prognosis of myelodysplastic syndromes (MDS). The objective of the current study was to investigate the prevalence and spectrum of autosomal monosomies in an unselected cohort of patients with known or suspected MDS by using retrospective analysis. The results showed that bone marrow cytogenetic studies (1532 cases) were performed between 2004 and 2012, and an abnormal karyotype was found in 538 cases (35.1%). In the 538 cases, 202 (37.5%) cases had autosomal monosomies including sole (n = 47, 23.3%), part of two (n = 33, 21.3%) or more (n = 122, 78.7%) anomalies. Almost all 22 autosomes were involved, but monosomy 7 was by far the most frequent, constituting 66.1% of all isolated monosomies and the highest fraction of those with two or more abnormalities. Other recurrent sole monosomies included chromosomes 20 (15.0%) and 13 (8.5%). Monosomy 13 (12.5%), 18 (8.3%), 20 (6.3%), 17 (7.3%), 21 (5.2%), 5 (5.2%) and 12 (5.2%) were also recurrent in the setting of 3 abnormalities. Bone marrow histology and clinical information were reviewed in all cases with isolated monosomy; associated clinical phenotypes were found in RCMD (n = 20, 13 were -7), RAEB (n = 12, 11 were -7), RA (n = 9, 3 were -7) and chronic myelomonocytic leukemia (CMML, n = 6, 4 were -7) cases. Sole monosomy 20 (n = 7, RA 3 case and RCMD 4 cases) was not detected in RAEB or CMML cases. It is concluded that the presence of at least 1 autosomal monosomy was documented in approximately 37.5% of all abnormal cases, which has potential impact on a more than trivial fraction of patients with MDS. The preponderance of monosomy 7 implicates a pathogenetic role for haploinsufficiency of genes associated with chromosome 7. The rarity of sole monosomy involving other chromosomes other than 7, 20, and 13 suggests that haploinsufficiency involving entire chromosomes is detrimental to cell survival, unless their effect is overcome by the presence of other genetic changes that are often associated with additional chromosomal abnormalities. The observation is consistent with the usually favorable prognostic profile associated with sole monosomy 20.
Abnormal Karyotype ; Chromosome Aberrations ; Chromosome Deletion ; Humans ; Karyotyping ; Monosomy ; Myelodysplastic Syndromes ; genetics ; Prognosis ; Retrospective Studies

OBJECTIVETo evaluate the effect of preimplantation genetic diagnosis (PGD) conducted for women who had Down syndrome pregnancy previously.

METHODSTrisomy 21 was diagnosed by using fluorescence in site hybridization (FISH) before embryo transfer in two women who had Down syndrome pregnancies. Each received one or two PGD cycles respectively.

RESULTSCase 1: one PGD cycle was conducted, two oocytes were fertilized and biopsied. One embryo is of trisomy 21 and the other of monosomy 21. No embryo was transferred. Case 2: two PGD cycles were conducted, in total, sixteen oocytes were fertilized and biopsied. Four embryos were tested to be normal, six of trisomy 21, and one of monosomy 21. Five had no signal. Four normal embryos were transferred but no pregnancy resulted.

CONCLUSIONFor couples who had pregnancies with Down syndrome previously, PGD can be considered, and has been shown to be an effective strategy.

Adult ; Chromosomes, Human, Pair 21 ; genetics ; Down Syndrome ; diagnosis ; genetics ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Male ; Monosomy ; Pregnancy ; Preimplantation Diagnosis

BACKGROUND: 3q21q26 syndrome includes chromosomal abnormalities of inv(3)(q21q26), t(3;3) (q21;q26), and ins(3;3)(q26;q21q26). It causes hematological diseases by the leukemogenic mechanism that the enhancer of ribophorin I gene in 3q21 induces the transcription of ecotropic viral integration site-1 gene in 3q26. Recently, it has been proposed that the 3q21q26 syndrome may be preceded by diabetes insipidus (DI), particularly when combined with monosomy 7, and is a unique disease entity. METHODS: From May 2001 to June 2006, a total of 5 patients with hematologic malignancy were found to have 3q21q26 syndrome and monosomy 7. Laboratory findings, clinical data, and association with DI were investigated. RESULTS: The rearrangement type of 3q21q26 was inv(3)(q21q26) in four patients and t(3;3)(q21; q26) in one. These patients' French American British types were AML M1, M2, M4 and M7, showing evident dysmegakaryopoiesis. Aberrant antigenic expressions of CD7 and CD56 were observed. The platelet count was relatively high as AML. All the five patients were refractory or in early relapse. Patient 5 was diagnosed with AML M7 20 days after being diagnosed with DI. While DI was well controlled with oral desmopressin, leukemia was refractory to chemotherapy. CONCLUSIONS: This study supports the recent opinion that 3q21q26 syndrome with monosomy 7 combined with DI is a disease of unique characteristics. In the relation between DI and monosomy 7 or 3q21q26 syndrome, there has been no explanation about how acquired abnormality of hematopoietic cells affects production of DDAVP by neurohormonal cells in hypothalamus. The mechanism needs further study, and this research should contribute to the understanding of genetic roles in leukemia appearing in different forms.
Adult ; Chromosome Disorders/*complications/*diagnosis/genetics ; *Chromosomes, Human, Pair 3 ; Diabetes Insipidus, Neurogenic/*complications ; Female ; Hematologic Neoplasms/*complications ; Humans ; Inversion, Chromosome ; Karyotyping ; Male ; Middle Aged ; Monosomy ; Prognosis ; Syndrome ; Translocation, Genetic