OBJECTIVE: We present mosaic distal 9p deletion at prenatal diagnosis in a pregnancy associated with a favorable fetal outcome.
METHODS: A 34-year-old, primigravid woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 46,XY, del(9)(p23)[8]/46,XY[17]. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes showed 43% mosaicism for the 9p24.3p23 deletion. Prenatal ultrasound suspected hypospadias and echogenic bowel. At 23 weeks of gestation, she was referred for genetic counseling, and repeat amniocentesis revealed a karyotype of 46,XY,del(9)(p23)[10]/46,XY[10]. The parental karyotypes were normal. Molecular genetic analysis on uncultured amniocytes revealed no uniparental disomy (UPD) 9 by quantitative fluorescence polymerase chain reaction (QF-PCR) and arr 9p24.3p23 × 1.55 (40%-50% mosaicism) by aCGH. At 27 weeks of gestation, she underwent the third amniocentesis which revealed a karyotype of 46,XY,del(9)(p23)[6]/46,XY[14]. Simultaneous aCGH analysis on the DNA extracted from uncultured amniocytes revealed the result of arr 9p24.3p23 (35% mosaicism). Prenatal ultrasound was normal. She was advised to continue the pregnancy, and a 3020-g phenotypically normal male baby was delivered at 41 weeks of gestation. At birth, the karyotypes of cord blood, umbilical cord and placenta were 46,XY,del(9)(p23)[7]/46,XY[37], 46,XY,del(9)(p23)[17]/46,XY[23] and 46,XY in 40/40 cells, respectively. When follow-up at age three months, the neonate was normal in phenotype and development. The peripheral blood had a karyotype of 46,XY,del(9)(p23)[3]/46,XY[37], and interphase fluorescence in situ hybridization (FISH) analysis on buccal mucosal cells showed 13% (13/102 cells) mosaicism for the distal 9p deletion.
CONCLUSIONS: Mosaic distal 9p deletion with a normal cell line at prenatal diagnosis can be associated with a favorable fetal outcome and perinatal progressive decrease of the aneuploid cell line.

OBJECTIVE: Kleefstra syndrome (KS), formerly known as 9q subtelomeric deletion syndrome, is characterized by multiple structural abnormalities. However, most fetuses do not have obvious abnormal phenotypes. In this study, the fetus with KS presented with multiple system structural anomalies, and we aimed to explore the genotype-phenotype correlations of KS fetuses.
METHODS: Multiple systematic structural anomalies, including severe intrauterine growth restriction (IUGR) and cardiac defects, were detected by ultrasound in the fetus at 33 + 5 weeks\' gestation. These abnormalities may be caused by the pathogenic deleted fragment at 9q34.3, including the euchromatic histone methyltransferase 1 (EHMT1) and collagen type V alpha 1 chain (COL5A1) genes, detected by copy number variation sequencing (CNV-seq).
CONCLUSIONS: It is essential for clinicians to perform CNV-seq combined with multidisciplinary consultation for suspected KS fetuses, especially those with multiple systematic structural anomalies.

Pericentric inversion of chromosome 9 (inv[9]) is a common chromosomal structural variant, but its impact on clinical outcomes remains debated. The screening criteria of sperm banks are rarely mentioned to individuals with inv(9). In this study, we evaluated the fertility of sperm donors with inv(9) who met eligibility criteria for sperm banks (inv[9]-eligible donors). From March 2004 to May 2022, chromosomal analysis of 16 124 sperm donors at CITIC-Xiangya Human Sperm Bank in Hunan Province (Changsha, China) found that 251 (1.6%) had chromosome variations, with inv(9) being the most prevalent at 1.1%. All 169 inv(9)-eligible donors were contacted to collect fertility outcome data, along with 206 eligible donors without inv(9) as controls. In addition, semen samples from inv(9)-eligible donors and eligible donors underwent assessments of sperm fluorescence in situ hybridization (FISH), mitochondrial membrane potential, DNA fragmentation index, acrosome integrity, reactive oxygen species (ROS), and sperm morphology. Results showed that inv(9) did not significantly increase reproductive risks overall. Despite detecting ROS level differences, the clinical impact may be insignificant. This study provides new data on the inv(9) population that can serve as a valuable reference for decision-making by sperm banks as well as for genetic counseling and clinical guidance for individuals carrying inv(9) variant.

Complete chromosome 9 trisomy (T9) is a rare and fatal chromosomal disorder. We performed non-invasive prenatal testing (NIPT) in a patient with threatened abortion symptoms and found that the fetal was at risk for complete chromosome 9 trisomy. This shows that NIPT has certain accuracy in detecting trisomy of chromosome 9, which provide options for prenatal diagnosis of rare chromosomal abnormalities.

It was to investigate the value of quantitative fluorescence PCR (QF-PCR) for the selection of specific short tandem repeat (STR) in prenatal diagnosis of fetal chromosomal diseases. Amniotic fluid (AF) and villus samples were obtained from 80 pregnant women at 16-20 weeks of gestation, and venous blood samples were obtained from 60 normal individuals to extract and prepare peripheral blood chromosome, AF cell chromosome, and villus cell chromosome samples for specific STR locus detection. It showed that the area ratio of AMX peak to AMY peak in the Genescan typing map of peripheral blood DNA of normal males was close to 1:1, while the Genescan typing map of peripheral blood DNA of normal females had only AMX peak and no AMY peak. Normal heterozygous individuals had an area ratio between 1 and 1.45 for venous blood, 1.002 and 1.27 for villous samples, and 1 and 1.35 for AF samples. The karyotype of a male fetus was 46, XY, inv [9] (p11: q13), and the structure of fetal chromosome 9 was inverted (interarm), and the site of structural inversion was band 1 in the short breech 1 region and band 3 in the long arm 1 region of chromosome 9. It suggested that QF-PCR can effectively identify the normal human body and cases by selecting specific STR locus detection, which has a good application value for prenatal diagnosis of fetal chromosomal diseases.

Many studies have suggested an association between 9p24 rs719725 polymorphism and colorectal cancer (CRC) risk, but with inconsistent results. This meta-analysis aimed to summarise the overall association of rs719725 polymorphism with CRC risk. Nine eligible articles with 21 case-control studies (16015 CRC patients and 19341 controls) on the rs719725 polymorphism and CRC susceptibility from four electronic databases (Web of Science, PubMed, SinoMed, and EMBASE) were retrieved and analysed. The association was evaluated with publication bias, pooled OR (odds ratio), and corresponding 95% CI (confidence interval). The pooled results indicated a significant association between the increased CRC risk and rs719725 polymorphism in dominant ([OR] 1.220, [95%CI] 1.161-1.282), recessive (1.166, 1.102-1.234), allele (1.142, 1.102-1.184), homozygous (1.306, 1.212-1.406), and heterozygous (1.18, 1.129-1.234) genetic models. The ethnicity-stratified analyses found a consistently significant association. In the stratification analysis with the source of controls, such significant association was also detected amid the population-based studies under the four former genetic models. Taken together, this meta-analysis indicates that rs719725 genetic variants are associated with an increased risk of CRC among Caucasians and population-based studies. Further relevant research is warranted to confirm these findings. Key Words: Colorectal cancer, rs719725, Polymorphism, Meta-analysis, Stratification analysis.

OBJECTIVE: To explore the genetic basis for a rare case of acute B-lymphocytic leukemia (B-ALL) with double Philadelphia chromosomes (Ph) and double derivative chromosome 9s [der(9)].
METHODS: A patient with double Ph and double der(9) B-ALL who presented at Shanghai Zhaxin Intergrated Traditional Chinese and Western Medicine Hospital in June 2020 was selected as the subject. Bone marrow morphology, flow cytometry, G-banding karyotyping, fluorescence in situ hybridization (FISH), genetic testing and chromosomal microarray analysis (CMA) were used to analyze bone marrow samples from the patient at various stages.
RESULTS: At initial diagnosis, the patient\'s bone marrow morphology and flow immunotyping have both supported the diagnosis of B-ALL. G-banded karyotyping of the patient indicated double Ph, in addition with hyperdiploid chromosomes involving translocations between chromosomes 9 and 22. BCR-ABL1 fusion gene was positive. Genetic testing at the time of recurrence revealed presence of a heterozyous c.944C>T variant in the kinase region of the ABL1 gene. FISH showed a signal for ABL1-BCR fusion on both chromosome 9s. CMA showed that the mosaicism homozygosity ratio of chromosome 9 was about 40%, and the mosaicism duplication ratio of chromosome 22 was about 43%.
CONCLUSIONS: Since both der(9) homologs were seen in 40% of cells, the possible mechanism for the double der(9) in this patient may be similar to that of double Ph, which might have resulted from non-disjunction during mitosis in the Ph chromosome-positive cell clone.

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.
CONCLUSIONS: Through combined cytogenetic and molecular genetic analysis, a sSMC derived from chromosome 9 was delineated, which has enabled genetic counseling for the couple.

暂无摘要。

OBJECTIVE: We present detection of maternal uniparental disomy (UPD) 9 in association with low-level mosaic trisomy 9 at amniocentesis in a pregnancy associated with intrauterine growth restriction (IUGR), an abnormal first-trimester maternal serum screening result, abnormal non-invasive prenatal testing (NIPT), maternal preeclampsia and a favorable outcome.
METHODS: A 37-year-old, primigravid woman underwent first-trimester maternal serum screening and NIPT at 11 weeks of gestation, which revealed a gene dosage increase in chromosome 9 and low levels of plasma protein-A (PAPP-A) and placental growth factor (PlGF) in maternal blood. The woman underwent amniocentesis at 16 weeks of gestation, which revealed a karyotype of 47,XX,+9[4]/46,XX[35] in cultured amniocytes. Simultaneous array comparative genomic hybridization (aCGH) analysis on uncultured amniocytes revealed a result of arr [GRCh37] (9) × 3 [0.14] (X) × 2, compatible with mosaic trisomy 9. The parental karyotypes were normal. Repeat amniocentesis was performed at 20 weeks of gestation. The cultured amniocytes had a karyotype of 47,XX,+9[1]/46,XX[23]. The uncultured amniocytes had a mosaic trisomy 9 level of 10.7% (12/112 cells) by interphase fluorescence in situ hybridization (FISH), a mosaic trisomy 9 level of 10-14% (log2 ratio = 0.1) by aCGH, and maternal uniparental isodisomy 9 by polymorphic DNA marker analysis. Prenatal ultrasound revealed IUGR, and the mother had preeclampsia. At 29 weeks of gestation, a 1054-g phenotypically normal baby was delivered because of preterm labor. The cord blood and umbilical cord had the karyotype of 46, XX and maternal UPD 9 and isodisomy 9, while the placenta had trisomy 9 of maternal origin. Postnatal FISH anlaysis on 101 buccal mucosal cells and 100 urinary cells at age three months detected no trisomy 9 signals. The baby was doing well at age six months.
CONCLUSIONS: Pregnancy with low-level mosaic trisomy 9 and maternal UPD 9 at amniocentesis can be associated with IUGR, maternal preeclampsia and a favorable outcome. Fetuses with maternal UPD 9 can be associated with an abnormal NIPT result concerning chromosome 9, an abnormal first-trimester maternal serum screening result (low PAPP-A and low PlGF) and mosaic trisomy 9 at amniocentesis.