New strategies for the treatment of carcinoma of unknown primary / 中华肿瘤杂志

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.

Guideline for the application of chromosomal microarray analysis in prenatal diagnosis (2023) / 中华妇产科杂志

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.

Value of chromosomal microarray analysis for the diagnosis of fetuses with anomalies of central nervous system / 中华医学遗传学杂志

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.

Clinical and genetic analysis of a fetus with 17q12 microdeletion syndrome / 中华医学遗传学杂志

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.

Clinical phenotype and genetic analysis of a child with 14q12q13 microdeletion syndrome manifesting as congenital hypothyroidism / 中华医学遗传学杂志

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.

Prenatal diagnosis and genetic analysis for two Chinese pedigrees carrying large fragment deletions of 13q21 / 中华医学遗传学杂志

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.

The value of chromosomal microarray analysis and fluorescence in situ hybridization for the prenatal diagnosis of chromosomal mosaicisms / 中华医学遗传学杂志

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.

Follow-up of fetuses with de novo copy number variations of unknown significance detected by chromosomal microarray analysis / 中华医学遗传学杂志

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.

Chromosomal microarray analysis of 17 patients with unbalanced reciprocal translocations / 中华医学遗传学杂志

OBJECTIVE@#To retrospectively analyze the results of chromosomal microarray analysis (CMA) and parental origins of unbalanced translocations among 17 patients, so as to provide reference for their genetic counseling.@*METHODS@#The results of CMA for 7 001 samples tested in Chengdu Women and Children's Central Hospital from January 2019 to January 2022 were retrospectively reviewed. Unbalanced reciprocal translocation was defined as two non-homologous chromosomes with lost and gained segments respectively or both with gained segments, and their parental origins were identified by parental chromosomal karyotyping and/or fluorescence in situ hybridization (FISH).@*RESULTS@#In total 17 unbalanced translocations were identified. In three cases, two non-homologous chromosomes both had gained segments, which constituted a derivative chromosome, with the total number of chromosomes being 47. In the remaining 14 cases, there was a terminal deletion on one chromosome and a terminal duplication on the other, 10 of which were confirmed by karyotyping, with the total number of chromosomes being 46. In the derivative chromosome, the lost segment was replaced by a gained segment from another chromosome. Among 15 cases undergoing parental origin analysis, 12 had paternal or maternal chromosomal abnormalities, including 11 balanced translocations and 1 unbalanced translocation. The unbalanced gametes therefore may form through meiosis. In 3 cases, the parental chromosomes were normal, indicating a de novo origin.@*CONCLUSION@#Discovery of terminal duplication and deletion or gained segments on two non-homologous chromosomes by CMA is suggestive of parental balanced translocation, which can facilitate genetic counseling and assessment the recurrence risk for subsequent pregnancies.

Clinical features and genetic analysis of two fetuses with ring chromosome 21 mosaicism / 中华医学遗传学杂志

OBJECTIVE@#To investigate the perinatal clinical phenotype and genetic characteristics of two fetuses with ring chromosome 21 mosaicisms.@*METHODS@#Two fetuses who were diagnosed at the Xiamen Maternal and Child Health Care Hospital in November 2021 were selected as the study subjects. Clinical data of the two fetuses were collected. Conventional G-banded karyotyping and chromosomal microarray analysis (CMA) were carried out for the fetuses and their parents.@*RESULTS@#Prenatal ultrasonography of fetus 1 has revealed absence of nasal bone, ventricular septal defect, persistent left superior vena cava, and mild tricuspid regurgitation. Chromosomal karyotyping was 46,X?,dic r(21;21)(p12q22;q22p12)[41]/45,X?,-21[9]. CMA has revealed a 30.00 Mb quadruplication at 21q11.2q22.3 and a 3.00 Mb deletion at 21q22.3. For fetus 2, ultrasonography has revealed pointed echo of the nasal bone. The fetus was found to have a karyotype of 46,X?,r(21)(p12q22)[83]/45,X?,-21[14]/46,X?,dic r(21;21)(p12q22;q22p12)[3]. CMA has revealed a 5.10 Mb quadruplication at 21q22.12q22.3 and a 2.30 Mb deletion at 21q22.3.@*CONCLUSION@#The perinatal phenotype of the two fetuses with ring chromosome 21 mosaicisms is related to the duplication of chromosomal segments near the breakpoints of the chromosomal deletions. The combined chromosomal karyotyping and CMA has enabled prenatal diagnosis and genetic counseling for these families.

Bioinformatics Analysis of Microarray Data in Myelodysplastic Syndrome Based on Gene Expression Omnibus Database / 中国实验血液学杂志

OBJECTIVE@#To identify the key genes and explore mechanisms in the development of myelodysplastic syndrome (MDS) by bioinformatics analysis.@*METHODS@#Two cohorts profile datasets of MDS were downloaded from Gene Expression Omnibus (GEO) database. Differentially expressed gene (DEG) was screened by GEO2R, functional annotation of DEG was gained from GO database, gene ontology (GO) enrichment analysis was performed via Kyoto Encyclopedia of Genes and Genomes (KEGG) database, and key genes were screened by Matthews correlation coefficient (MCC) based on STRING database.@*RESULTS@#There were 112 DEGs identified, including 85 up-regulated genes and 27 down-regulated genes. GO enrichment analysis showed that biological processes were mainly enriched in immune response, etc, cellular component in cell membrane, etc, and molecular function in protein binding, etc. KEGG signaling pathway analysis showed that main gene enrichment pathways were primary immunodeficiency, hematopoietic cell lineage, B cell receptor signaling pathway, Hippo signaling pathway, and asthma. Three significant modules were screened by Cytoscape software MCODE plug-in, while 10 key node genes (CD19, CD79A, CD79B, EBF1, VPREB1, IRF4, BLNK, RAG1, POU2AF1, IRF8) in protein-protein interaction (PPI) network were screened based on STRING database.@*CONCLUSION@#These screened key genes and signaling pathways are helpful to better understand molecular mechanism of MDS, and provide theoretical basis for clinical targeted therapy.

Prenatal utility of parental source verification on the interpretation of copy number variation identified by chromosomal microarray analysis / 中华医学遗传学杂志

OBJECTIVE@#To investigate the parental-origin verification of fetal CNVs in the setting of prenatal diagnosis.@*METHODS@#182 families were recruited in this study. All the pregnant women underwent transabdominal amniocentesis or cordocentesis, and the amniotic fluid or cord blood samples were then subjected to karyotyping and chromosomal microarray analysis (CMA) respectively. The peripheral blood specimens of fetal parents were also tested by CMA for determining the parental-origin of fetal CNVs. Then we followed up the clinical outcomes of the fetuses.@*RESULTS@#Of the 182 fetuses, 163 (89.6%) had parental-origin CNVs, and 19 (10.4%) had de novo CNVs. 149 (91.4%) of the parental-origin CNVs were classified into the variant of uncertain significance (VUS) before parental-origin tests. After parental source verification, 137 (91.9%) of these VUS cases were changed into likely benign cases. Among the 163 cases of parental-origin CNVs, 122 (74.8%) fetuses were born healthy. Among the 19 de novo cases, 9 of these families chose to terminate the pregnancy.@*CONCLUSION@#The majority of inherited CNVs detected by CMA had a tendency to be benign, and the parental source verification could assist the elucidation of clinical significance of CNVs in prenatal diagnosis.

Clonagem, expressão recombinante e validação por microarray de proteínas alimentares potencialmente alergênicas / Cloning, recombinant expression and validation by microarray of potentially allergenic food proteins

A maioria das respostas alérgicas a alimentos é mediada por IgE, que pode ser detectada para fins de diagnóstico da alergia alimentar. No entanto, para isso é necessário que alérgenos purificados estejam disponíveis para a elaboração dos diferentes formatos de ensaio, inclusive por microarray, que se constitui em uma ferramenta bastante útil para análise simultânea, e também para a identificação de reatividade cruzada. A esse respeito, é imprescindível ampliar a plataforma de alérgenos que possam ser empregados para a confecção de microarrays. Atualmente, alguns alimentos que constituem objeto de interesse na clínica em função do número de casos de alergia, e sobre os quais as informações a respeito dos alérgenos são escassas, são: abacaxi, mamão, mandioca e manga. Assim, o objetivo desse trabalho foi clonar, expressar e purificar proteínas potencialmente alergênicas de alimentos de importância regional. Após confirmadas por ensaios imunológicos, essas proteínas foram utilizadas na construção e validação de um microarray através de ensaios com os soros de pacientes alérgicos aos alimentos selecionados. Para atingir esse objetivo, foram selecionadas proteínas potencialmente alergênicas coincidentes, apontadas tanto pela similaridade com espécies taxonomicamente mais próximas, quanto pela técnica 2D Western Blotting acoplada à espectrometria de massas. Dezenove proteínas, sendo 4 de abacaxi, 5 de mamão, 6 de mandioca e 4 de manga, foram expressas em Pichia pastoris, purificadas e impressas em um microarray. Após incubar essas proteínas com os soros dos pacientes alérgicos aos alimentos estudados, 18 proteínas mostraram-se potencialmente alergênicas. Além disso, foi observada reatividade cruzada entre proteínas dos alimentos estudados e também em relação ao látex e outros frutos

The majority of allergic reactions to foods is IgE-mediated, which can be detected for the diagnosis of food allergy. However, purified allergens are necessary to produce different kinds of allergy tests, including microarray, which is a useful tool for simultaneous analysis, as well as for the identification of cross-reactivity. In this respect, it is essential to expand the platform of allergens to include them on microarrays. Nowadays, some foods that are object of interest in the clinical area in Brazil and it is necessary a further evaluation about their potential allergens, since there is a limited information about them, are: pineapple, papaya, cassava and mango. Therefore, the aim of this study was cloning, expressing and purifying potentially allergenic proteins of important Brazilian foods. After confirmed by immunological tests, these proteins were used in microarray production and validation by assays with sera from allergic patients to the selected foods. Achieving this goal, matching potentially allergenic proteins were selected, which were identified by comparison among taxonomically closer species (in silico) and 2D Western Blotting coupled with Mass Spectrometry. Nineteen proteins: 4 from pineapple, 5 from papaya, 6 from cassava and 4 from mango were expressed in Pichia pastoris, purified and printed on a microarray. After incubating those proteins with sera from allergic patients to the selected foods, 18 proteins were detected as potentially allergenic. In addition, cross-reactivity was observed among the proteins from the studied foods, and also regarding to the latex and other fruits

Correlation of fetal ventriculomegaly with copy number variations and pregnancy outcome / 中华医学遗传学杂志

OBJECTIVE@#To assess the correlation of borderline fetal ventriculomegaly with genomic copy number variations (CNVs) and outcome of pregnancy.@*METHODS@#For 84 singleton pregnancies diagnosed with VM, chromosomal microarray analysis (CMA) was carried out to detect the CNVs of the fetal genome. Outcome of the pregnancy and neonatal development were analyzed. The pregnant women were divided into mild group (10-12 mm), moderate group (12-15 mm) and severe group (>= 15 mm) based on the severity of fetal ventriculomegaly. The detection rate of pathogenic CNVs and pregnancy outcome were compared. Multivariate logistic regression was carried out to analyze the predictors for pregnancy outcome.@*RESULTS@#Respectively, 24, 28 and 32 fetuses were assigned into the mild, moderate and severe groups. CMA has detected 15 cases of chromosomal abnormalities, including 11 pathogenic CNVs and 4 abnormal karyotypes. Abnormal pregnancy outcomes were found in 20 fetuses, including 12 with hydrocephalus and 8 with chromosomal microdeletion syndromes. A significant difference was found in the detection rate of fetal pathogenic CNVs and abnormal pregnancy outcome among the three groups (P<0.05). Multivariate logistic regression analysis showed that the largest change of lateral ventricle width (OR = 1.868, 95%CI = 1.120-3.116) and the extent of lateral ventricle widening (OR = 1.571, 95%CI = 1.120-2.206) were the key factors affecting the outcome of pregnancy (P<0.05).@*CONCLUSION@#Borderline fetal VM is associated with the risk of pathogenic CNVs and adverse pregnancy outcome. A comprehensive examination is required after prenatal ultrasound diagnosis, which is conducive to prenatal consultation and prognostic evaluation of the fetus.

Analysis of related phenotype of prenatal cases with copy number variations in various region of 22q11.2 / 中华医学遗传学杂志

OBJECTIVE@#To analyze the prenatal ultrasound phenotypes of copy number variations (CNVs) in different regions of 22q11.2, their parental original, and pregnancy outcome.@*METHODS@#Prenatal phenotypes of 25 cases with CNVs of the 22q11.2 region detected by chromosomal microarray analysis (CMA) was reviewed, which including There were 13 deletions and 12 duplications. Multiplex ligation-dependent probe amplification(MLPA) was carried out to determine their parental origin. All cases were followed up for their pregnancy outcome and postnatal growth.@*RESULTS@#Among the 25 cases, the ultrasound phenotypes of those involving the TBX1 gene were mostly cardiovascular system abnormalities, the ultrasound phenotypes of cases involving CRKL gene are mostly polycystic renal dysplasia. The ultrasound phenotypes of CNVs in the distal region (involving the SMARCB1 gene) are nervous system abnormalities. 12 cases (48%) of CNVs were de novo in origin. Five cases were lost during follow-up,12 had opted to terminate the pregnancy, 8 fetuses were born,7 with normal growth and development, 1 case with CNV in A-D region was abnormal.Prenatal ultrasound showed abnormalities in the cardiovascular system consistent with postnatal ultrasound, in addition with dysphagia and growth retardation.@*CONCLUSION@#Prenatal phenotypes of the 22q11.2 region CNVs are diverse, which may be related to gene function. NT thickening may be used as an early ultrasound finding of proximal 22q11.2 CNV. More research is still required to delineate the nature of CNVs and gene function, so as to facilitate genetic counseling.

Value of chromosomal microarray analysis for the prenatal diagnosis of pregnancy with high risk signaled by non-invasive prenatal testing / 中华医学遗传学杂志

OBJECTIVE@#To explore the value of chromosomal microarray analysis (CMA) for the diagnosis of fetuses with high risk signaled by non-invasive prenatal testing (NIPT).@*METHODS@#From June 2017 to August 2019, 628 pregnant women with high risk signaled by NIPT underwent invasive prenatal diagnosis. Amniotic fluid or cord blood samples were subjected to chromosomal karyotyping analysis or CMA. Pregnancy outcome and postnatal conditions of the fetuses were followed up.@*RESULTS@#The positive predictive value for trisomy 21, trisomy 18, trisomy 13, sex chromosome aneuploidy, other rare trisomies and copy number variants (CNVs) among the 628 women were 86.4% (127/147), 41.7% (30/72), 12.9% (4/31), 43.7% (101/231), 16.5% (14/85) and 52.2% (35/67), respectively. In 218 samples with normal karyotype, 5.5% (12/218) of additional pathogenic CNVs and 2.3% (5/218) of loss of heterozygosity were detected by CMA.@*CONCLUSION@#CMA combined with karyotyping analysis can be used as first-tier test for prenatal diagnosis for women with high-risk signaled by NIPT.

Experience and lessons on guiding and governing clinical applications of chromosome microarray analysis in the United States / 中华医学遗传学杂志

Chromosome microarray analysis (CMA) has become the first-tier testing for chromosomal abnormalities and copy number variations (CNV). This review described the clinical validation of CMA, the development and updating of technical standards and guidelines and their diagnostic impacts. The main focuses were on the development and updating of expert consensus, practice resources, and a series of technical standards and guidelines through systematic review of case series with CMA application in the literature. Expert consensus and practice resource supported the use of CMA as the first-tier testing for detecting chromosomal abnormalities and CNV in developmental and intellectual disabilities, multiple congenital anomalies and autism. The standards and guidelines have been applied to pre- and postnatal testing for constitutional CNV and tumor testing for acquired CNV. CMA has significantly improved the diagnostic yields but still needs to overcome its technical limitations and face challenges of new technologies. Guiding and governing CMA through expert consensus, practice resource, standards and guidelines in the United States has provided effective and safe diagnostic services to patients and their families, reliable diagnosis on related genetic diseases for clinical database and basic research, and references for clinical translation of new technologies.

Prenatal diagnosis of a fetus with 8q13.3 microdeletion through chromosomal microarray analysis / 中华医学遗传学杂志

OBJECTIVE@#To assess the value of chromosomal microarray analysis (CMA) for the prenatal diagnosis of a fetus with structural anomaly detected by ultrasonography.@*METHODS@#The fetus and its parents were subjected to chromosomal karyotyping and CMA analysis.@*RESULTS@#The fetus was found to carry a 46,XN,t(8;11)(q21.2;q13) translocation which was inherited from its mother. CMA has found no copy number variations (CNVs) in both parents but a de novo 2.00 Mb microdeletion in the fetus at 8q13.3.@*CONCLUSION@#CMA is capable of detecting microdeletions and microduplications in fetuses with translocations detected by karyotyping analysis.

Value of chromosomal microarray analysis for fetuses with duodenal obstruction / 中华医学遗传学杂志

OBJECTIVE@#To assess the value of chromosomal microarray analysis (CMA) for fetal duodenal obstruction (DO).@*METHODS@#Fifty-one fetuses with DO identified by prenatal ultrasound were divided into DO only group and DO with other anomaly group. CMA was carried out on amniotic fluid or umbilical blood samples, and the outcome of pregnancy of all cases were followed up.@*RESULTS@#Eight fetuses (15.7%) were found with genomic abnormalities, which included 3 chromosomal aneuploidies and 5 copy number variations (CNVs), including one 17q12 microduplication syndrome, one 13q21.33q31.1 microdeletion, one 13q21.32q22.3 deletion, one 13q21.2q31.1 deletion and one 1q43q44 duplication. EDNRB from 13q and HNF1B from 17q12 are candidate genes for fetal DO. No significant difference was found in the detection rate of pathogenic CNVs between the DO only and DO with other anomaly groups (9.5% vs.11.1%, P> 0.05). There were 39 live borns, 1 stillbirth, and 11 artificial abortions (8 with abnormal CMA results).@*CONCLUSION@#There is a correlation between fetal DO and abnormal copy number of the genome, for which prenatal diagnosis is necessary. CMA not only can detect microdeletions/microduplications, but also identify pathogenic genes, which can facilitate prenatal diagnosis, genetic counseling and prognosis for the fetus.

Association of fetal cardiac structural abnormalities and chromosomal aneuploidies and copy number variations / 中华医学遗传学杂志

OBJECTIVE@#To investigate the association of fetal cardiac structural abnormalities with chromosomal aneuploidies and copy number variations (CNVs) in amniocytes.@*METHODS@#328 pregnant women were subjected to fetal ultrasonography and chromosomal microarray analysis (CMA). Based on the fetal heart structure, the subjects were divided into normal (n=273) and abnormal groups (n=55). The detection rates of chromosomal aneuploidies and CNVs were compared between the two groups. Spearman method was used to assess the association between the results and fetal cardiac structural abnormalities.@*RESULTS@#The detection rates for chromosomal aneuploidies and CNVs in the abnormal group were significantly higher than that in the normal group (P< 0.05), and the incidence of fetal cardiac structural abnormalities was strongly associated with chromosomal aneuploidies and CNVs (P< 0.05).@*CONCLUSION@#Fetal chromosomal aneuploidies and CNVs are strongly associated with cardiac structural abnormalities.