Analysis of clinical phenotype and pathogenic variant of a fetus with Cornelia de Lange syndrome type II / 中华医学遗传学杂志

OBJECTIVE@#To explore the prenatal ultrasonographic features and genetic basis for an abortus suspected for type II Cornelia de Lange syndrome (CdLS2).@*METHODS@#A fetus diagnosed with CdLS2 at the Shengjing Hospital Affiliated to China Medical University on September 3, 2019 was selected as the study subject. Clinical data of the fetus and family history was collected. Following induced labor, whole exome sequencing was carried out on the abortus. Candidate variant was verified by Sanger sequencing and bioinformatic analysis.@*RESULTS@#Prenatal ultrasonography (33 weeks of pregnancy) has revealed multiple anomalies in the fetus, which included slightly widened cavity of septum pellucidum, blurred corpus callosum, slightly reduced frontal lobe volume, thin cortex, fusion of lateral ventricles, polyhydramnios, small stomach bubble, and digestive tract atresia. Whole exome sequencing has revealed a heterozygous c.2076delA (p.Lys692Asnfs*27) frameshifting variant in the SMC1A gene, which was found in neither parent and was rated as pathogenic based on the guidelines of American College of Medical Genetics and Genomics (ACMG).@*CONCLUSION@#The CdLS2 in this fetus may be attributed to the c.2076delA variant of the SMC1A gene. Above finding has provided a basis for genetic counseling and assessment of reproductive risk for this family.

TCN1 Deficiency Inhibits the Malignancy of Colorectal Cancer Cells by Regulating the ITGB4 Pathway

Background/Aims@#This study aimed to investigate the biological function and regulatory mechanism of TCN1 in colorectal cancer (CRC). @*Methods@#We studied the biological function of TCN1 by performing gain-of-function and loss-offunction analyses in HCT116 cell lines; examined the effects of TCN1 on the proliferation, apoptosis, and invasion of CRC cells; and determined potential molecular mechanisms using HCT116 and SW480 CRC lines and mouse xenotransplantation models. Tumor xenograft and colonization assays were performed to detect the tumorigenicity and metastatic foci of cells in vivo. @*Results@#TCN1 knockdown attenuated CRC cell proliferation and invasion and promoted cell apoptosis. Overexpression of TCN1 yielded the opposite effects. In addition, TCN1-knockdown HCT116 cells failed to form metastatic foci in the peritoneum after intravenous injection. Molecular mechanism analyses showed that TCN1 interacted with integrin subunit β4 (ITGB4) to positively regulate the expression of ITGB4. TCN1 knockdown promoted the degradation of ITGB4 and increased the instability of ITGB4 and filamin A. Downregulation of ITGB4 at the protein level resulted in the disassociation of the ITGB4/plectin complex, leading to cytoskeletal damage. @*Conclusions@#TCN1 might play an oncogenic role in CRC by regulating the ITGB4 signaling pathway.

A case of BMP2 gene variation-caused short stature, facial dysmorphism and skeletal anomalies with or without cardiac anomaly syndrome / 中华围产医学杂志

This article reported the genetic analysis of a case diagnosed with fetal micrognathia and cleft palate by mid-trimester ultrasound in two consecutive pregnancies. In the first pregnancy, the pregnant woman delivered a full-term boy transvaginally, who died two weeks after birth and was diagnosed with Pierre Robin sequence (PRS). Chromosome karyotype and genomic copy number variation. In the second pregnancy, the woman underwent amniocentesis due to suspected PRS presenting by fetal cleft palate, micrognathism, and additional ultrasound anomalies. No abnormalities were detected in fetal karyotype or genomic copy number variation. Whole-exome sequencing, bioinformatics analysis, and Sanger sequencing suggested that both the fetus and the firstborn boy inherited a possible pathogenic variant of c.79delG p.E27Sfs*24 in the BMP2 gene from the mother. The pregnancy was terminated after the genetic consultation. Fetal phenotypes in the two fetuses were similar, indicating that short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomaly in the pedigree were caused by the heterozygous variant of c.79delG p.E27Sfs*24 in the BMP2 gene.

Expression, functional mechanism and therapy application of long noncoding RNA in β-thalassemia / 中南大学学报(医学版)

β-thalassemia (β-thal) is one of the most common genetic diseases in the world, its pathogenesis is extremely complex and there is no effective treatment at present. The birth of children with moderate and severe β-thal brings economic pressure to families, social medical and health services. Long noncoding RNA (lncRNA) is a type of noncoding protein transcripts with a length greater than 200 nucleotides, which is involved in a variety of biological processes, such as cell proliferation, differentiation and chromosome variation and plays an important role in the epigenetic and post-transcriptional regulation of genes. It has potential value in the diagnosis, prevention and treatment of β-thal. LncRNA possesses the characteristics such as tissue specificity, cell specificity, developmental stage specificity, space-time specificity and disease specificity, and its complex interaction network has become a challenge to translate research results into clinical practice. Taking lncRNA as an entry point, in-depth understanding of the function of lncRNA in β-thal and explanation of its related regulatory mechanisms will provide theoretical basis for targeting treatment of β-thal, which can improve the diagnosis and treatment of β-thal.

Prenatal ultrasonographic manifestations and genetic analysis of eight fetuses with 16p11.2 microdeletions / 中华医学遗传学杂志

OBJECTIVE@#To analyze the intrauterine phenotype and genotype of eight fetuses carrying a 16p11.2 microdeletion.@*METHODS@#5100 fetuses undergoing routine prenatal diagnosis were subjected to single nucleotide polymorphism-based microarray (SNP-array) analysis. Fetuses harboring a 16p11.2 microdeletion were analyzed for their ultrasonographic characteristics.@*RESULTS@#Eight fetuses were found to harbor a microdeletion in the 16p11.2 region. Among these, six had a typical 500-600 kb deletion, while the remaining two had an atypical 220 kb deletion at the distal part of 16p11.2. Four fetuses showed vertebral malformations, two had mild left ventriculomegaly, one had hydrocephalus, and one had pulmonary valve stenosis with regurgitation. The parents of five fetuses have accepted pedigree verification, and the results confirmed that the 16p11.2 microdeletions carried by fetuses all had a de novo origin.@*CONCLUSION@#The intrauterine phenotypes of fetuses carrying a 16p11.2 microdeletion may be variable, and the deletion can be effectively detected with the SNP-array assay.

The value of combined detection of HbA2 and HbF for the screening of thalassemia among individuals of childbearing ages / 中华医学遗传学杂志

OBJECTIVE@#To assess the application value of combined detection of HbA2 and HbF for the screening of thalassemia among a population of childbearing age in Quanzhou, Fujian, and determine the optimal cut-off values for the region.@*METHODS@#Capillary hemoglobin electrophoresis and genetic testing for α and β globin gene mutations were simultaneously carried out on 11 428 patients with suspected thalassemia. Statistical methods were used to analyze the distribution of various types of thalassemia and compare the performance of HbA2 and HbF measurement for the screening of various types of thalassemia. The optimal cut-off values for HbA2 and HbF were determined with the ROC curves.@*RESULTS@#4591 patients with α, β, and αβ compound thalassemia were identified by genetic testing. The most common genotypes for α and β thalassemia included --SEA/αα and β654/βN, β41-42/βN, and β17/βN. The ROC curves were drawn to compare the performance of HbA2 screening for α-, β-, αβ-compound, static α-, mild α-, and intermediate α-thalassemia, and the maximum area under the curves was 0.674, 0.984, 0.936, 0.499, 0.731, 0.956, and the optimal cut-off values for HbA2 were 2.45%, 3.25%, 3.65%, 2.95%, 2.55%, 1.75%, respectively.@*CONCLUSION@#HbA2 is an efficient indicator for identifying intermediate types of α-, β-, and αβ compound thalassemia. The combination of HbA2 and HbF measurement can effectively detect carriers for β-thalassemia mutations.

Study on clinical features and diagnostic methods of prenatal Wolf-Hirschhorn syndrome / 中华医学遗传学杂志

OBJECTIVE@#To investigate the clinical features of fetuses with Wolf-Hirschhorn syndrome(WHS) and explore the diagnostic methods and prenatal ultrasound characteristics and provide evidence for prenatal genetic counseling.@*METHODS@#We retrospectively analyzed 5 cases of WHS fetuses diagnosed from March 2016 to February 2020, and analyzed the results of chromosomal karyotype analysis and chromosomal microarray analysis (CMA) of the fetuses.@*RESULTS@#Five cases of WHS were detected by CMA, four cases were detected by karyotype analysis. Prenatal ultrasound revealed 4 abnormalities, of which 3 had intrauterine growth restriction, and only 1 had abnormalities of the maxillofacial region. The sequence of the fragments was 4p16.3p16.1 with a loss of 6.5 Mb, 4p16.3p15.32 with a loss of 15.6 Mb combined with 2p25.3 increased by 906kb, 4p16.3p15.31 with a loss of 20.4 Mb, 4p16.p15.1 with a loss of 35 Mb and 4p16.3p14 with a loss of 37 Mb.@*CONCLUSION@#Fetal growth restriction may be one of the early manifestations of WHS. Absence of fetal facial abnormality by prenatal ultrasound screening cannot exclude WHS. Karyotype analysis may miss the diagnosis of WHS, while combined CMA techniques can improve the diagnostic accuracy.

CD31 and D2-40 Contribute to Peritoneal Metastasis of Colorectal Cancer by Promoting Epithelial-Mesenchymal Transition

Background/Aims@#Colorectal cancer (CRC) patients often exhibit peritoneal metastasis, which negatively impacts their prognosis. CD31 and D2-40 have recently been suggested to be predictors of breast cancer prognosis, but their role in colorectal peritoneal metastasis (CRPM) remains unknown. @*Methods@#The expression profiles of CD31 and D2-40 were analyzed in CRC patients with or without CRPM and in CRC cell lines with increasing metastatic potential. Overexpression and short hairpin RNA knockdown assays were performed in CRC cells, and the effects of these alterations on epithelial-mesenchymal transition (EMT) in vitro, growth of xenograft tumors in vivo, and peritoneal metastasis potential in a mouse model of CRPM were examined. @*Results@#The expressions of CD31 and D2-40 were upregulated in CRC tumor tissues and was elevated further in tumor tissues from patients with CRPM. CD31 and D2-40 expression levels exhibited increasing trends parallel to the EMT potential of CRC cells. CD31 and D2-40 are essential for CRC cell EMT in vitro as well as for xenograft tumor growth and peritoneal metastasis in vivo. @*Conclusions@#CD31 and D2-40 contribute to CRPM by promoting EMT and may serve as prognostic markers and therapeutic targets for CRC, particularly in patients with peritoneal metastasis.

Prenatal diagnosis of five fetuses with 7q11.23 microdeletion or microduplication / 中华医学遗传学杂志

OBJECTIVE@#To investigate the ultrasonographic findings and genetic testing methods for fetuses carrying copy number variants (CNVs) of 7q11.23 region.@*METHODS@#Prenatal cases with 7q11.23 microdeletion/microduplication detected by single nucleotide polymorphism array (SNP array) from January 2016 to June 2020 were retrospectively analyzed, including fetal ultrasound, chromosomal karyotype, SNP array, pregnancy outcome and follow-up. Literature on 7q11.23 CNVs identified upon prenatal diagnosis was also reviewed.@*RESULTS@#Five fetuses were found with 7q11.23 CNVs, including 3 microdeletions and 2 microduplications. Of them, 4 had ultrasonographic anomalies. The karyotypes of all fetuses were normal. Of three 7q11.23 microdeletions, two were de novo, while the remaining one couple did not accept parental verification. Of two 7q11.23 microduplications, one was de novo and the another was inherited from a phenotypic normal father. Three 7q11.23 microdeletions and one de novo 7q11.23 microduplication were electively aborted. One fetus carrying paternally inherited 7q11.23 microduplication was delivered full term. Follow-up found the infant had a normal phenotype.@*CONCLUSION@#Fetuses with 7q11.23 microdeletions or microduplications showed phenotypic heterogeneity. SNP array can accurately detect 7q11.23 CNVs, thereby provide accurate information for prenatal diagnosis and genetic counseling.

Prenatal ultrasonic characteristics and genetic analysis of fetuses with chromosome 22q11 microdeletion syndrome / 中华医学遗传学杂志

OBJECTIVE@#To analyze the prenatal ultrasonic characteristics and genetic features of 14 fetuses with chromosome 22q11 microdeletion syndrome (22q11DS).@*METHODS@#4989 fetuses were analyzed by using single nucleotide polymorphism array (SNP array) in the Fujian Maternal and Child Health Hospital from November 2016 to November 2019.@*RESULTS@#SNP array showed that 11 fetuses had classic 3 Mb microdeletion in 22q11 region, one fetus had 2.0 Mb microdeletion, and two fetuses had 1.0 Mb microdeletion. The 1.0 Mb microdeletion in 22q11 region contains SNAP29 and CRKL genes, which may increase the risk of congenital renal malformation and cardiovascular malformation.@*CONCLUSION@#Prenatal ultrasonic characteristics of fetuses with 22q11 microdeletion syndrome vary, and SNP array is a powerful tool to diagnose such diseases, which can provide accurate genetic diagnosis and enable prenatal diagnosis.

Impact of confined placental mosaicism on non-invasive prenatal testing and pregnancy outcomes / 中华医学遗传学杂志

OBJECTIVE@#To assess the impact of confined placental mosaicism (CPM) on non-invasive prenatal testing (NIPT) and pregnancy outcomes.@*METHODS@#Copy number variation sequencing (CNV-seq) and single nucleotide polymorphism array (SNP-array) were carried out on placental specimen sampled from eight pregnancies with confirmed false-positive NIPT results. The impact of CPM on NIPT and pregnancy outcomes were analyzed based on the laboratory tests and clinical characteristics.@*RESULTS@#Five of the eight cases with false-positive NIPT results were proven to be CPM involving trisomy 9, 13, 21, 22, and X, respectively. The mosaic ratios for different placental regions have varied from 4% to 80%. Two fetuses with confirmed CPM showed fetal growth restriction (FGR) and additional ultrasound abnormalities, 1 fetus showed only FGR. The remaining two fetuses showed normal growth.@*CONCLUSION@#NIPT is highly sensitive to CPM, whilst CPM is an important cause for false-positive NIPT result. CPM may be associated with FGR. Investigation of the presence of CPM is important for both pre- and post-test genetic counseling and management of the pregnancy.

Effectiveness of non-invasive prenatal screening for the detection of fetal sex chromosome anomalies / 中华医学遗传学杂志

OBJECTIVE@#To evaluate the efficacy of non-invasive prenatal screening (NIPS) for fetal sex chromosome anomalies.@*METHODS@#A retrospective analysis was carried out for 20 802 women undergoing NIPS screening. For 165 cases suspected for fetal sex chromosomal anomalies, the results of invasive prenatal diagnosis were obtained.@*RESULTS@#Among the 165 cases suspected for fetal sex chromosome anomalies, 129 have accepted invasive prenatal diagnosis, and 45 were confirmed, which yielded a positive predictive value of 34.88%. These included 16 cases of 47,XYY, 10 cases of 47,XXY, 6 cases of 45,X/46,XX, 5 cases of 47,XXX, 3 cases of 45,X, 1 case of 45,X/46,X,i(X)(q10), 1 case of 45,X/46,X,del(X)(q22), 1 case of 46,X,del(X)(q22), 1 case of 46,X,del(X)(p11) and 1 case of Xp22.31 1.2 Mb deletion.@*CONCLUSION@#NIPS has limited value for detecting fetal sex chromosome anomalies. Karyotyping analysis combined with other diagnostic techniques can offer effective prenatal diagnosis for suspected cases.

Value of copy number variation analysis and chromosomal karyotyping for the diagnosis of children with intellectual disability/developmental delay / 中华医学遗传学杂志

OBJECTIVE@#To assess the value of copy number variations (CNVs) and chromosomal karyotyping analysis for patients with intellectual disability/developmental delay (ID/DD).@*METHODS@#Chromosomal karyotype analysis was applied to 530 children diagnosed with ID/DD. Single nucleotide polymorphism array (SNP-array) was further applied for 120 children with unknown etiology.@*RESULTS@#Among the 530 children with ID/DD, 104 (19.62%) were detected with chromosomal abnormalities. For the 120 children analyzed by SNP-array, 44 (36.67%) were detected with CNVs, among which 20 were predicted as pathogenic, 6 as likely pathogenic, 10 as variants of unknown significance, 7 as likely benign,and 1 as loss of heterozygosity.@*CONCLUSION@#SNP-array can facilitate delineation of the etiology of patients with ID/DD, which may provide a basis for their prognosis, consultation and clinical intervention.

Variant analysis for patients from Fujian area with Hong Kong αα type thalassemia / 中华医学遗传学杂志

OBJECTIVE@#To determine the frequency of Hong Kong αα (HK αα) gene in α3.7 positive samples among carriers from Fujian area.@*METHODS@#Routine genetic testing for thalassemia was carried out for 10145 patients with positive screening results. Single PCR and two-round nested PCR were utilized to detect HK αα among 507 patients with α3.7/αα and 2 patients for whom electrophoresis showed α3.7, -αSEA and normal α2 alleles. Reverse dot blot test was used for detecting non-deletional α-thalassemia and β-thalassemia variants.@*RESULTS@#Among the 507 patients with α3.7/αα, HK αα was identified in 35 cases, which included 25 HK αα/αα, 5 HK αα/α3.7, 4 HK αα/αα with heterozygous CD41/42 (HBB: c.126_129delCTTT) variant, 1 HK αα/αα with IVS-II-654 (HBB: c.316_197C>T) heterozygous variant. One patient was confirmed to have α3.7/anti4.2 genotype. The two cases with α3.7, -αSEA and normal α2 alleles were confirmed to be HK αα/--SEA. The frequency of HK αα genotype in Fujian area was therefore 7.27% among patients with α3.7 and 0.36% in the general population.@*CONCLUSION@#A certain proportion of HK αα has been detected in Fujian area, which will enable more accurate diagnosis and genetic counseling.

Prenatal diagnosis and clinical analysis of two fetuses with Cat-eye syndrome / 中华医学遗传学杂志

OBJECTIVE@#To determine the origin of supernumerary small marker chromosomes (sSMCs) carried by two fetuses.@*METHODS@#Single nucleotide polymorphism array (SNP-array) and fluorescence in situ hybridization (FISH) analysis were carried out on cells cultured from the amniotic fluid samples.@*RESULTS@#SNP-array analysis showed both fetuses to be arr[hg19]22q11.1q11.21(16 888 899-18 649 190)×4, with a duplicated 1.7 Mb region (16 888 899-18 649 190) leading to partial tetrasomy of 22q11.1-22q11.21. FISH confirmed that both fetuses were 47,XN,+mar.ish idic(22)(q11.2) (RP11-958H20 ++),which suggested a diagnosis of Cat-eye syndrome (CES). The appearance of abortuses were consistent with the diagnosis of CES.@*CONCLUSION@#Two fetuses with CES were diagnosed by genetic testing. The latter has provided a basis for genetic counseling.

Analysis of hematological phenotype and genotype of Hb Q-Thailand in Fujian area / 中华医学遗传学杂志

OBJECTIVE@#To explore the hematological phenotype and genotype of hemoglobin Q-Thailand in Fujian area.@*METHODS@#Genomic DNA was extracted from peripheral venous blood samples of patients. Suspected samples were screened by hematological parameters analysis and verified with DNA sequencing.@*RESULTS@#In 35 patients suspected with Hb Q-Thailand, 20 were confirmed, which included one case compounded with heterozygous β mutation and one compounded with Hb New York.@*CONCLUSION@#Analysis of hematological phenotype and genotype of Hb Q-Thailand can faciliate genetic counseling for patients from Fujian area.

Genetic testing and prenatal diagnosis of X-linked ichthyosis in two pedigrees / 中华围产医学杂志

Objective To analyze genetic testing and prenatal diagnosis of two pedigrees with X-linked ichthyosis.Methods Karyotyping,bacterial artificial chromosomes-on-BeadsTM (BoBs),fluorescence in situ hybridization (FISH) and single nucleotide polymorphism array (SNP-array) were used to detect amniotic fluid and peripheral blood specimens of two pedigrees,one with and one without known family history of ichthyosis.Clinical data was collected and analyzed as well.Results (1) The pedigree without known family history:Prenatal BoBs showed that the XC1 probe of fetus Ⅳ-12 was from 0.36 to 0.50,suggesting the presence of microdeletion.SNP-array analysis of gravida Ⅲ-13 showed a 1.68 Mb copy number deletion at Xp22.31 and four missing Online Mendelian Inheritance in Man (OMIM) genes (HDHD1,STS,VCX and PNPLA4).Fetal SNP-array revealed a deletion of arr[hg19] Xp22.31 (6 455 151-8 135 644)× 0,indicating a maternally inherited one.FISH analysis verified the deletion in STS gene in fetus Ⅳ-12,whose karyotype was 46,XY.The gravida's female cousin (Ⅲ-21) and nephew (Ⅳ-14) also had STS gene deletion,which size was the same as that from the gravida and the fetus.Fetus (Ⅳ-12) was delivered at term by cesarean section with normal skin,but an extensive white scales appeared on the abdomen one week after birth and the symptom was aggravated when the weather was dry.The infant was followed up to eight months old and no other clinical symptoms were found.(2) The pedigree with known family history:SNP-array revealed that a 1.2 Mb copy number deletion at Xp22.31 and four missing OMIM genes (HDHD1,STS,VCX and PNPLA4) were detected in pregnant women (Ⅲ-21),proband (Ⅳ-16) and fetus (Ⅳ-17).FISH analysis of the fetus verified the deletion in STS gene.The karyotype of the fetus was 46,XY.Fetus Ⅳ-17 was delivered at term by cesarean section with normal skin,but white scales widely appeared on the abdomen ten days after birth.The infant was followed up to four months old and no other clinical symptoms were found.Conclusion Molecular genetic techniques such as BoBs,FISH and SNP array are used in combination in this study to provide genetic testing and prenatal diagnosis to two XLI pedigrees,which is helpful for clinical diagnosis and genetic counseling.

CT-imaging-based anatomical and three-dimensional modeling of the head and neck arterial vessels of the miniature pig / 中国比较医学杂志

Objective To investigate the anatomical structure of arterial vessels in the head and neck of miniature pigs and the related application of vascular cast specimens,and the technology of three-dimensional model reconstruction by CT imaging. Methods A vascular cast specimen of a miniature pig head and neck was made by a 128-slice spiral CT scanning,and a three-dimensional model of the arterial vessels in the head and neck of the miniature pig was reconstructed. Results The cast specimen clearly showed the distribution and running characteristics of the arteries in the head and neck of a miniature pig. The three-dimensional digital model was realistic and stereoscopic,showing the running and distribution of arteries from multiple angles and layers. Conclusions The distribution and running characteristics of arterial vessels in the head and neck of a miniature pig have been investigated by the combination of cast specimen and three-dimensional digital model,providing a morphological reference for the establishment of pig cerebrovascular models in respects of both solid specimen and virtualized model.

The prevalence and genetic characterization of 22750 cases of beta-thalassemia in Fujian Province / 中华检验医学杂志

Objective To analyze the molecular characterization and prevalence of beta-thalassemia in Fujian Province .Methods RDBwas applied to identify 17 point mutations of beta gene and 3 point mutations of alpha gene .Gap-PCRwas applied to identify 3 deletions of alpha gene , MLPA and DNA sequecing were applied to identify the rare mutational genotype of beta-thalassemia.Results 3515 cases (15.45％)ofβ-thalassemia were confirmed.15 genotypes were found in the studied subjects .βIVS-2-654(C→T)/βN, βCD41-42(-TCTT)/βN, βCD17(A→T)/βN, β-28(A→G)/βN, βCD27-28( +C)/βN, and βCD26(G→A)/βN were the mostcommon genotypes in Fujian Province , accounting for 41.76％, 30.50％, 12.46％, 5.46％, 2.93％and 1.82％respectively , It was found that the total frequency of them was 94.93％in our study.13 cases of deletional β-thalassemia were detected , including 6 cases of Southeast Asia subtype ( SEA-HPFH) , 6 cases of Chinese subtype Gγ(Aγδβ)0 and 1 case of 1.35kb deletion(NG-000007.3:g.69997-71353 del 1357) in one subject .13 cases of rareβ-thalassemia were detected , including Hb J-Bankok in 8 subjects and Hb New York in 5 subjects were diagnosed .Conclusions As a high-risk area forβ-thalassaemia, the detection of deletional β-thalassemia and rare β-thalassaemia subtypes should be screened in addition to the common β-thalassemia genes , so as to demonstrate the results of β-thalassemia gene detection in this region .Those screening results are useful for genetic counseling and can effectively reduce the birth of children with moderate to severe β-thalassaemia .

Prenatal diagnosis of a fetus with Miller-Dieker syndrome / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To report on prenatal diagnosis of a fetus with Miller-Dieker syndrome (MDS) and explore its genotype - phenotype correlation.</p><p><b>METHODS</b>Chromosome karyotyping, bacterial artificial chromosome on beads (BACs-on-Beads, BoBs), fluorescence in situ hybridization (FISH), and single nucleotide polymorphism microarray (SNP array) were applied in conjunction for the prenatal diagnosis of a fetus with abnormal ultrasound findings.</p><p><b>RESULTS</b>A 17p13.3 microdeletion was detected with the BoBs assay, and the result was confirmed by FISH. With the SNP array, the deletion was mapped to chromosome 17, with its range determined to be 5.2 Mb. On high-resolution banding analysis and BoB assay, the deletion was not found in either parent.</p><p><b>CONCLUSION</b>The combined use of BoBs, FISH and SNP array has enabled prenatal diagnosis of a fetus with MDS. Attention should be paid to microdeletions and microduplications which can be missed by conventional chromosomal karyotyping analysis.</p>