OBJECTIVE: To assess the value of chromosomal microarray analysis (CMA) for the detection of low-level mosaicisms in amniotic fluid samples, and to retrospectively analyze the rare cases of mosaicisms. METHODS: Chromosomal karyotype of the fetus was determined by G-banding analysis of cultured amniotic fluid cells. CMA was used to detect copy number variation of fetal chromosomes, and fluorescence in situ hybridization (FISH) was used to determine the proportion of fetal chromosomal mosaicisms in uncultured amniotic fluid cells. RESULTS: Among 825 prenatal samples, 4 cases of true fetal mosaicisms were detected, which yielded an incidence of 0.48%. Two cases were sex chromosomal mosaicisms, and two were autosomal mosaicisms, which involved chromosomes 8 and 9, respectively. All cases were verified by G-banding analysis of cultured amniotic fluid cells, CMA, and/or FISH. CONCLUSION CMA has a great value for detecting low-level mosaicisms in amniotic fluid samples, though the positive results need to be verified by other techniques and should be interpreted with caution. The review of rare cases can provide a basis for prenatal genetic counseling.
Humans ; Female ; Amniotic Fluid/metabolism* ; Pregnancy ; Mosaicism/embryology* ; Prenatal Diagnosis/methods* ; Adult ; In Situ Hybridization, Fluorescence ; Microarray Analysis/methods* ; Karyotyping ; Retrospective Studies ; Male

OBJECTIVE: To explore the detection rate of copy number variations (CNVs) in fetuses with isolated Congenital anomalies of the kidney and urinary tract (CAKUT) and pregnancy outcomes in order to provide a basis for genetic counseling. METHODS: One hundred and eighty eight fetuses who underwent chromosomal microarray analysis (CMA) due to isolated CAKUT detected by prenatal ultrasonography at Qingdao Women and Children's Hospital from January 2021 to December 2024 were selected as the study subjects. According to the ultrasound findings, the fetuses were divided into 8 groups, including renal parenchymal dysplasia group, renal cystic dysplasia group, simple renal parenchymal echo enhancement group, abnormal development of renal collecting system group, duplicated kidney group, ectopic kidney group, horseshoe kidney group, and bladder/posterior urethral abnormalities group. The detection of CNVs was retrospectively analyzed, and the pregnant women were followed up to summarize their pregnancy outcomes. 2 test (or Fisher's exact probability method) was used to compare the CNV detection rates between the groups. This study was approved by the Medical Ethics Committee of the Qingdao Women and Children's Hospital (Ethics No.: QFELL-YJ-2025-85). RESULTS: Among the 188 fetuses with isolated CAKUT, 23 CNVs (12.23%) were detected, of which 13 cases (6.91%) were pathogenic and 10 cases were rated as variants of unknown significance (VOUS). Among the 8 groups, the three groups with the highest proportion were renal cystic dysplasia group, renal metaplasia group, and renal parenchymal dysplasia group. The detection rates of pathogenic CNVs in the three groups were 1.79% (1/56), 6.78% (4/59), and 16.67% (5/30), respectively, with statistically significant differences (P < 0.05). Parental verification was conducted on 12 fetuses detected with the CNVs, confirming that 2 cases were de novo and 10 were inherited from parents with a normal phenotype. After genetic counseling, the parents of 9 fetuses opted to terminate the pregnancy, while 11 chose to continue with the pregnancy, and 3 were lost to follow-up. At the time of last follow-up, the youngest offspring was 5 months old and the oldest was 3 years and 11 months old. One child had renal aplasia, and two were born with hydronephrosis, which have been cured through surgery. The remainders had no obvious abnormality with their growth and development. CONCLUSION CMA testing has important value for prenatal diagnosis of isolated CAKUT. In this study, the detection rate of pathogenic CNVs has increased sequentially in fetuses with renal cystic developmental abnormalities, renal collecting system developmental abnormalities, and renal parenchymal dysplasia, while there was no significant difference in the detection rate of CNVs. For fetuses with isolated CAKUT detected by prenatal ultrasound, CMA testing should be considered, and reasonable pregnancy decisions should be made based on the results of prenatal ultrasound and parental verification.
Humans ; Female ; Pregnancy ; Prenatal Diagnosis/methods* ; DNA Copy Number Variations/genetics* ; Kidney/abnormalities* ; Adult ; Ultrasonography, Prenatal ; Urogenital Abnormalities/diagnosis* ; Microarray Analysis/methods* ; Retrospective Studies ; Urinary Tract/abnormalities* ; Fetus ; Pregnancy Outcome ; Vesico-Ureteral Reflux

After the promulgation of the first edition of expert consensus on the application of chromosomal microarray analysis (CMA) technology in prenatal diagnosis in 2014, after 8 years of clinical and technical development, CMA technology has become a first-line diagnosis technology for fetal chromosome copy number deletion or duplication abnormalities, and is widely used in the field of prenatal diagnosis in China. However, with the development of the industry and the accumulation of experience in case diagnosis, the application of CMA technology in many important aspects of prenatal diagnosis, such as clinical diagnosis testimony, data analysis and genetic counseling before and after testing, needs to be further standardized and improved, so as to make the application of CMA technology more in line with clinical needs. The revision of the guideline was led by the National Prenatal Diagnostic Technical Expert Group, and several prenatal diagnostic institutions such as Peking Union Medical College Hospital were commissioned to write, discuss and revise the first draft, which was discussed and reviewed by all the experts of the National Prenatal Diagnostic Technical Expert Group, and was finally formed after extensive review and revision. This guideline is aimed at the important aspects of the application of CMA technology in prenatal diagnosis and clinical diagnosis, from the clinical application of evidence, test quality control, data analysis and interpretation, diagnosis report writing, genetic counseling before and after testing and other work specifications are elaborated and introduced in detail. It fully reflects the integrated experience, professional thinking and guidance of the current Chinese expert team on the prenatal diagnosis application of CMA technology. The compilation of the guideline for the application of CMA technology in prenatal diagnosis will strive to promote the standardization and advancement of prenatal diagnosis of fetal chromosome diseases in China.
Female ; Humans ; Pregnancy ; Asian People ; Chromosome Aberrations ; Chromosome Deletion ; Chromosome Duplication/genetics* ; DNA Copy Number Variations/genetics* ; Fetal Diseases/genetics* ; Genetic Counseling ; Microarray Analysis ; Prenatal Care ; Prenatal Diagnosis ; Practice Guidelines as Topic

Carcinoma of unknown primary (CUP) is a kind of metastatic tumor whose primary origin cannot be identified after adequate examination and evaluation. The main treatment modality of CUP is empiric chemotherapy, and the median overall survival time is less than 1 year. Compared with immunohistochemistry, novel method based on gene expression profiling have improved the sensitivity and specificity of CUP detection, but its guiding value for treatment is still controversial. The approval of immune checkpoint inhibitors and pan-cancer antitumor agents has improved the prognosis of patients with CUP, and targeted therapy and immunotherapy based on specific molecular characteristics are the main directions of future research. Given the high heterogeneity and unique clinicopathological characteristics of CUP, "basket trial" is more suitable for clinical trial design in CUP.
Humans ; Neoplasms, Unknown Primary/genetics* ; Carcinoma/drug therapy* ; Gene Expression Profiling/methods* ; Microarray Analysis ; Prognosis

OBJECTIVE: To assess the value of chromosomal microarray analysis (CMA) for the diagnosis of fetuses with anomalies of the central nervous system (CNS) and summarize the outcome of the pregnancies and follow-up. METHODS: A total of 636 fetuses from June 2014 to December 2020 who were referred to the Prenatal Diagnosis Center of Nanjing Drum Tower Hospital due to abnormal CNS prompted by ultrasound were selected as the research subjects. Based on the ultrasound findings, the fetuses were divided into ventricular dilatation group (n = 441), choroid plexus cyst group (n = 41), enlarged posterior fossa group (n = 42), holoprosencephaly group (n = 15), corpus callosum hypoplasia group (n = 22), and other anomaly group (n = 75). Meanwhile, they were also divided into isolated (n = 504) and non-isolated (n = 132) groups based on the presence of additional abnormalities. Prenatal samples (amniotic fluid/chorionic villi/umbilical cord blood) or abortus tissue were collected for the extraction of genomic DNA and CMA assay. Outcome of the pregnancies and postnatal follow-up were summarized and subjected to statistical analysis. RESULTS: In total 636 fetuses with CNS anomalies (including 89 abortus tissues) were included, and 547 cases were followed up. The overall detection rate of CMA was 11.48% (73/636). The detection rates for the holoprosencephaly group, ACC group, choroid plexus cyst group, enlarged posterior fossa group, ventricular dilatation group and other anomaly group were 80% (12/15), 31.82% (7/22), 19.51% (8/41), 14.29% (6/42), 7.48% (33/441) and 9.33% (7/75), respectively. Compared with the isolated CNS anomaly group, the detection rate for the non-isolated CNS anomaly group was significantly higher (6.35% vs. 31.06%) (32/504 vs. 41/132) (χ² = 62.867, P < 0.001). Follow up showed that, for 52 fetuses with abnormal CMA results, 51 couples have opted induced labor, whilst 1 was delivered at full term with normal growth and development. Of the 434 fetuses with normal CMA results, 377 were delivered at full term (6 had developmental delay), and 57 couples had opted induced labor. The rate of adverse pregnancy outcome for non-isolated CNS abnormal fetuses was significantly higher than that of isolated CNS abnormal fetuses (26.56% vs. 10.54%) (17/64 vs. 39/370) (χ² = 12.463, P < 0.001). CONCLUSION Fetuses with CNS anomaly should be tested with CMA to determine the genetic cause. Most fetuses with negative CMA result have a good prognosis, but there is still a possibility for a abnormal neurological phenotype. Fetuses with CNS abnormalities in conjunct with other structural abnormalities are at increased risk for adverse pregnancy outcomes.
Female ; Pregnancy ; Humans ; Holoprosencephaly ; Prenatal Diagnosis/methods* ; Central Nervous System ; Fetus/abnormalities* ; Nervous System Malformations/genetics* ; Microarray Analysis ; Central Nervous System Diseases ; Cysts ; Chromosome Aberrations ; Ultrasonography, Prenatal/methods*

OBJECTIVE: To analyze the prognosis of fetuses identified with de novo variants of unknown significance (VOUS) by chromosome microarray analysis (CMA). METHODS: A total of 6 826 fetuses who underwent prenatal CMA detection at the Prenatal Diagnosis Center of Drum Tower Hospital from July 2017 to December 2021 were selected as the study subjects. The results of prenatal diagnosis, and outcome of fetuses identified with VOUS of de novo origin were followed up. RESULTS: Among the 6 826 fetuses, 506 have carried VOUS, of which 237 were detected for the parent-of-origin and 24 were found to be de novo. Among the latters, 20 were followed up for 4 to 24 months. Four couples had opted elective abortion, 4 had developed clinical phenotypes after birth, and 12 were normal. CONCLUSION Fetuses with VOUS should be continuously follow-up, in particular those carrying de novo VOUS, in order to clarify their clinical significance.
Pregnancy ; Female ; Humans ; DNA Copy Number Variations ; Follow-Up Studies ; Prenatal Diagnosis/methods* ; Chromosomes ; Microarray Analysis/methods* ; Fetus ; Chromosome Aberrations

OBJECTIVE: To assess the value of chromosomal microarray analysis (CMA) and fluorescence in situ hybridization (FISH) for the prenatal diagnosis of chromosomal mosaicisms. METHODS: A total of 775 pregnant women who had visited the Prenatal Diagnosis Center of Yancheng Maternal and Child Health Care Hospital from January 2018 to December 2020 were selected as study subjects. Chromosome karyotyping analysis and CMA were carried out for all women, and FISH was used to validate the suspected mosaicism cases. RESULTS: Among the 775 amniotic fluid samples, karyotyping has identified 13 mosaicism cases, which yielded a detection rate of 1.55%. Respectively, there were 4, 3, 4 and 2 cases for sex chromosome number mosaicisms, abnormal sex chromosome structure mosaicisms, abnormal autosomal number mosaicisms and abnormal autosomal structure mosaicisms. CMA has only detected only 6 of the 13 cases. Among 3 cases verified by FISH, 2 cases were consistent with the karyotyping and CMA results, and clearly showed low proportion mosaicism, and 1 case was consistent with the result of karyotyping but with a normal result by CMA. Eight pregnant women had chosen to terminate the pregnancy (5 with sex chromosome mosaicisms and 3 with autosomal mosaicisms). CONCLUSION For fetuses suspected for chromosomal mosaicisms, CMA, FISH and G-banding karyotyping should be combined to determine the type and proportion of mosaicisms more precisely in order to provide more information for genetic counseling.
Female ; Pregnancy ; Humans ; Mosaicism ; In Situ Hybridization, Fluorescence ; Chromosome Disorders/genetics* ; Prenatal Diagnosis/methods* ; Chromosome Aberrations ; Sex Chromosome Aberrations ; Microarray Analysis/methods* ; Chromosomes

OBJECTIVE: To explore the strategies of prenatal diagnosis and genetic counseling for fetuses of two families with large deletions of 13q21. METHODS: Two singleton fetuses who were diagnosed with chromosome 13 microdeletions by non-invasive prenatal testing (NIPT) at Ningbo Women and Children's Hospital in March 2021 and December 2021 respectively were selected as the study subjects. Chromosomal karyotyping and chromosomal microarray analysis (CMA) were carried on amniotic samples. Peripheral blood samples were collected from the two couples for CMA assay to determine the origin of abnormal chromosomes identified in the fetuses. RESULTS: The karyotypes of the two fetuses were both normal. CMA revealed that they have respectively harbored heterozygous deletions spanning 11.935 Mb at 13q21.1q21.33 and 10.995 Mb at 13q14.3q21.32, which were respectively inherited from their mother and father. Both deletions had low gene density and lacked haploinsufficient genes, and were predicted to be likely benign variants based on database and literature search. Both couples had opted to continue with the pregnancy. CONCLUSION The deletions of the 13q21 region in both families may be of benign variants. As the follow-up time was short, there was no sufficient evidence for the determination of pathogenicity, though our finding may still provide a basis for the prenatal diagnosis and genetic counseling.
Pregnancy ; Child ; Female ; Humans ; Pedigree ; East Asian People ; Prenatal Diagnosis ; Chromosome Aberrations ; Karyotyping ; Microarray Analysis ; DNA Copy Number Variations

OBJECTIVE: To analyze the clinical phenotype and genetic etiology for a child featuring congenital hypothyroidism (CH). METHODS: Whole exome sequencing (WES), copy number variation (CNV) sequencing and chromosomal microarray analysis (CMA) were carried out for a newborn infant who had presented at Linyi People's Hospital for CH. Clinical data of the child was analyzed, in addition with a literature review. RESULTS: The main characteristics of the newborn infant had included peculiar face, vulvar edema, hypotonia, psychomotor retardation, recurrent respiratory tract infection with laryngeal wheezing and feeding difficulties. Laboratory test indicated hypothyroidism. WES suggested a CNV deletion on chromosome 14q12q13. CMA further confirmed a 4.12 Mb deletion at chromosome 14q12q13.3 (32649595_36769800), which has encompassed 22 genes including NKX2-1, the pathogenic gene for CH. The same deletion was found in neither of her parents. CONCLUSION Through the analysis of clinical phenotype and genetic variant, the child was diagnosed with 14q12q13.3 microdeletion syndrome.
Female ; Humans ; Congenital Hypothyroidism/genetics* ; DNA Copy Number Variations ; Phenotype ; Syndrome ; Microarray Analysis

OBJECTIVE: To explore the clinical phenotype and genetic characteristics of a fetus with 17q12 microdeletion syndrome. METHODS: A fetus with 17q12 microdeletion syndrome who was diagnosed at Huzhou Maternal & Child Health Care Hospital in June 2020 was selected as the study subject. Clinical data of the fetus was collected. The fetus was subjected to chromosomal karyotyping and chromosomal microarray analysis (CMA). To determine the origin of fetal chromosomal abnormality, its parents were also subjected to CMA assay. The postnatal phenotype of the fetus was also investigated. RESULTS: Prenatal ultrasound revealed polyhydramnios and fetal renal dysplasia. The fetus was found to have a normal chromosomal karyotype. CMA has detected a 1.9 Mb deletion in the 17q12 region, which has encompassed five OMIM genes including HNF1B, ACACA, ZNHIT3, CCL3L1 and PIGW. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the 17q12 microdeletion was predicted as pathogenic copy number variation (CNV). CMA analysis has detected no pathogenic CNV in both parents. After birth, the child was found to have renal cysts and abnormal brain structure. Combined with the prenatal findings, the child was diagnosed with 17q12 microdeletion syndrome. CONCLUSION The fetus has 17q12 microdeletion syndrome presenting as abnormalities of the kidney and central nervous system, which are strongly correlated with functional defects of the deletion region involving the HNF1B and other pathogenic genes.
Female ; Pregnancy ; Humans ; Chromosome Deletion ; DNA Copy Number Variations ; Chromosome Disorders/genetics* ; Kidney ; Fetus ; Microarray Analysis ; Prenatal Diagnosis