OBJECTIVE: To analyze four patients with a 16q22 fragile site with miscarriage or infertility by using cytogenetic methods. METHODS: Four patients presented at Northwest Women's and Children's Hospital between January 2022 and December 2024 were selected as the study subjects. Peripheral blood samples were collected from the patients and subjected to G-banded chromosomal karyotyping, among whom two were also subjected to copy number variation (CNV) sequencing. This study has been approved by the Ethics Committee of the Hospital (Ethics No. 2020-022). RESULTS: The chromosomal karyotypes of the patients were mos 46,XX,fra(16)(q22)[26]/47,XX,del(16)(q22),+chrb(16)(q22)[4]/46,XX,del(16)(q22)[3]/46,XX[91], mos 46,XY,fra(16)(q22)[21]/46,XY,del(16)(q22)[3]/46,XY[76], mos 46,XX,fra(16)(q22)[21]/ 46,XX,del(16)(q22)[4]/46,XX[75] and mos 46,XX,fra(16)(q22)[16]/46,XX,del(16)(q22)[7]/47,XX,del(16)(q22),+chrb(16)(q22)[6]/47,XX,fra(16)(q22),+chrb(16)(q22)[3]/46,XX[68], respectively. CNV sequencing of patients 2 and 4 revealed no deletion or duplication on chromosome 16. CONCLUSION Identification of the 16q22 fragile site has facilitated genetic counseling for these patients.
Humans ; Chromosome Fragile Sites/genetics* ; Chromosomes, Human, Pair 16/genetics* ; DNA Copy Number Variations/genetics* ; Karyotyping

OBJECTIVE: To explore the genetic basis for a Fra(16)(q22)/FRA16B fragile site in a female with secondary infertility. METHODS: The 28-year-old patient was admitted to Chengdu Women's and Children's Central Hospital on October 5, 2021 due to secondary infertility. Peripheral blood sample was collected for G-banded karyotyping analysis, single nucleotide polymorphism array (SNP-array), quantitative fluorescent polymerase chain reaction (QF-PCR) and fluorescence in situ hybridization (FISH) assays. RESULTS: The patient was found to harbor 5 mosaic karyotypes involving chromosome 16 in a total of 126 cells, which yielded a karyotype of mos 46,XX,Fra(16)(q22)[42]/46,XX,del(16)(q22)[4]/47,XX,del(16),+chtb(16)(q22-qter)[4]/46,XX,tr(16)(q22)[2]/46,XX[71]. No obvious abnormality was found by SNP-array, QF-PCR and FISH analysis. CONCLUSION A female patient with FRA16B was identified by genetic testing. Above finding has enabled genetic counseling of this patient.
Female ; Humans ; In Situ Hybridization, Fluorescence ; Chromosome Fragile Sites ; Karyotyping ; Karyotype ; Infertility

OBJECTIVE: To analyze a patient with infertility and a fragile site found at 16q22 by using cytogenetic methods. METHODS: Peripheral blood sample was taken from the patient and subjected to chromosomal karyotyping and single nucleotide polymorphism microarray (SNP-array) analysis. RESULTS: The patient was found to be a mosaicism for a fragile site at 16q22, which has a variable morphology and cannot be induced by folic acid treatment. No abnormality was found by SNP-array analysis. CONCLUSION A rare fragile site, which can be induced without folic acid treatment, has been identified at 16q22. The strategy of assisted reproduction for such individuals is yet to be explored.
Chromosome Fragile Sites ; Chromosome Fragility ; Chromosomes, Human, Pair 16 ; Genetic Testing ; Humans ; Karyotyping ; Mosaicism

PURPOSE: Genetic factors are known to be important in the etiology of bipolar disorder (BD). The fragile sites (FSs) are a very interesting subject for the study of clinical disorders. The aim of this study was to evaluate fragile sites seen in patients with bipolar disorder and find a correlation between some fragile sites and bipolar disorder. PATIENTS AND METHODS: The frequencies of folate sensitive FSs were compared in short-term whole blood cultures from bipolar patients and from normal individuals. RESULTS: The rate of FS expression in the patients was considerably higher than in the controls (p < 0.001). Several chromosome regions including 1p36, 1q21, 1q32, 3p25, 7q22, 7q32, 11q23, 12q24, 13q32, 14q24, Xp22 and Xq26 were represented considerably more often in the patients than in the controls (p value between 0.001 to 0.036). Among these FSs, the sites 1p36, 1q21, 3p25, 7q22, 7q32, and 14q24 were not observed in other studies. CONCLUSION: These regions can be the most active of hot spots in the genomes of bipolar patients, and may harbor important genes associated with BD.
Adolescent ; Adult ; Bipolar Disorder/*genetics ; Chromosome Fragile Sites/drug effects/*genetics ; Chromosome Fragility/drug effects/*genetics ; Chromosomes, Human/*genetics ; Cytogenetics ; Female ; Folic Acid/pharmacology ; Genetic Predisposition to Disease ; Humans ; Male ; Middle Aged ; Young Adult

BACKGROUNDWWOX and FHIT are two candidate tumor suppressor genes located in active fragile sites, the damage of which has been associated with the development of breast cancer. The association of the expression of these genes and the development of breast cancer has not been fully explored. We evaluated mRNA and protein expression of WWOX and FHIT in breast tissue with normal histological appearances, atypical ductal hyperplasia, ductal carcinoma in situ, and invasive cancer to see if a progressive decline in expression was present.

METHODSReverse transcription-polymerase chain reaction and Western blotting were used to evaluate the specimens for mRNA and protein expression, including 28 specimens with normal tissue, 28 specimens with atypical ductal hyperplasia, 33 specimens with ductal carcinoma in situ, and 51 specimens with invasive ductal carcinoma.

RESULTSCompared with in situ and invasive cancer specimens, both normal and atypical hyperplasia specimens had greater rates of detectable mRNA (WWOX rate ratio = 2.95, 95% CI 1.24 - 7.08; FHIT rate ratio = 4.58, 95% CI 1.82 - 11.81) and Western blotting detectable protein (WWOX rate ratio = 4.12, 95% CI 1.63 - 10.73; FHIT rate ratio = 3.76, 95% CI 1.44 - 10.06). For both proteins, differences between normal and atypical hyperplasia specimens and between in situ and invasive carcinoma specimens were explainable by chance (P > 0.05 for each analysis). Within each histological category, differences among fractions of specimens showed that FHIT and WWOX mRNA and protein expression were explainable by chance (P > 0.05 for each analysis).

CONCLUSIONExpression of FHIT and WWOX decreases along with breast tissue progress from a normal histological appearance to atypical ductal hyperplasia, in situ cancer, and the final invasive cancer.

Acid Anhydride Hydrolases ; analysis ; genetics ; Breast ; pathology ; Breast Neoplasms ; genetics ; Chromosome Fragile Sites ; Female ; Genes, Tumor Suppressor ; Humans ; Hyperplasia ; Neoplasm Proteins ; analysis ; genetics ; Oxidoreductases ; analysis ; genetics ; Tumor Suppressor Proteins ; analysis ; genetics ; WW Domain-Containing Oxidoreductase

OBJECTIVETo analyze the molecular coining of a fragile site-associated gene.

METHODSGenomic Chinese hamster ovary (CHO) DNA library was constructed using high molecular weight CHO DNA partially digested with MboI restriction enzyme from cultured CHO cells. Screening of genomic DNA library followed the established procedures. Genomic CHO in the positive clones was sequenced. Appropriate primers were designed for the reverse transcriptase-polymerase chain reactions (RT-PCR). The RT-PCR products were cloned into a pCRII TOPO vector and confirmed by DNA sequencing. Antibodies were prepared using synthetic peptides as antigens by immunizing the rabbits. Immunohistochemical analyses were performed to evaluate the expression of the novel gene in different tissues.

RESULTSTo investigate the molecular mechanism underlying the initial events of mdr1a amplification, we cloned 1q31 fragile site DNA. Strikingly, we found that this fragile site contained a novel gene which was designated as a fragile site-associated (FSA) gene. FSA encoded an unusually large mRNA of approximately16 kb. Full-length human FSA cDNA was cloned. FSA mRNA was expressed in many cultured cells and tissue types. Immunohistochemical analyses also revealed an expression pattern of the encoded proteins in postmitotic, well-differentiated epithelial compartments of many organs, including colon, mammary glands, ovary, prostate, and bladder.

CONCLUSIONFSA plays an important role in regulating mammalian epithelial cell growth and differentiation.

Animals ; CHO Cells ; Cell Line ; Chromosome Fragile Sites ; genetics ; Cloning, Molecular ; Cricetinae ; Cricetulus ; HCT116 Cells ; HT29 Cells ; Humans