OBJECTIVETo apply single nucleotide polymorphism microarray (SNP array) for the detection of genome-wide copy number variations(CNVs) in fetuses with malformations and women with an adverse reproductive history, and to explore the correlation of rare CNVs with the clinical manifestations.

METHODSAmniotic fluid and umbilical cord blood samples were collected from 314 women with singleton pregnancy. SNP array was performed on samples where chromosomal abnormalities were excluded after G-banding analysis.

RESULTSPathological CNVs were detected in 8.91% (28/314) of all samples, which included 11 duplications, 9 deletions, 4 loss of heterozygosity (LOH), and 4 conjoined deletions and duplications. The sizes of duplications and deletions were between 0.47 Mb and 16.7 Mb, and between 0.16 Mb and 13.3 Mb, respectively. Fifteen CNVs were mapped to the regions of microdeletion or microduplication syndromes or regions associated with clinical manifestations, while the remainder 13 were considered benign or variant of uncertain significance.

CONCLUSIONA proportion of fetuses with malformations and women with an adverse reproductive history may be attributed to CNVs, half of which are mapped with to the regions of well known syndromes. SNP array may facilitate discovery of new syndromes and provide a basis for genetic counseling and prenatal diagnosis.

Adult ; Chromosome Aberrations ; Chromosome Disorders ; diagnosis ; embryology ; genetics ; DNA Copy Number Variations ; Female ; Fetal Diseases ; diagnosis ; genetics ; Humans ; Infant ; Infant, Newborn ; Male ; Polymorphism, Single Nucleotide ; Pregnancy ; Pregnancy Complications ; diagnosis ; genetics ; Prenatal Diagnosis ; Reproductive History ; Young Adult

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

No abstract available.
Asian Continental Ancestry Group/*genetics ; Chromosome Deletion ; Chromosome Disorders/complications/*diagnosis ; Chromosomes, Human, Pair 18 ; Cyanosis/*etiology ; Female ; Heart Septal Defects, Atrial/complications/*diagnosis ; Humans ; Infant ; Karyotyping ; Republic of Korea