Prenatal diagnosis and genetic counseling of 1q21.1 distal microdeletion/microduplication in 14 fetuses / 中华围产医学杂志

Objective:To explore the clinical phenotypes, pregnancy outcomes, and follow-up of fetuses with 1q21.1 distal microdeletion/microduplication, and to provide a basis for prenatal and genetic counseling.Methods:This was a retrospective study involving 14 singleton fetuses with 1q21.1 distal microdeletion/microduplication that were prenatally diagnosed by karyotype analysis and chromosomal microarray analysis (CMA) at Wuxi Maternity and Child Health Care Hospital from January 2017 to June 2022. The results of ultrasound and genetic analysis, pregnancy outcome after genetic counseling, and postnatal follow-up were summarized using descriptive statistical methods.Results:All 14 fetuses had normal karyotypes. Out of the 14 cases, CMA indicated 1q21.1 distal microdeletion in eight cases and 1q21.1 distal microduplication in six cases. The fragments ranged from 813 kb to 4.48 Mb, all of which contained the key region of 1q21.1 microdeletion/microduplication syndrome and were pathogenic copy number variations (CNV). Among eight fetuses with distal 1q21.1 microdeletion, four cases had abnormal prenatal ultrasound findings, including one case with overlapping fingers of left hand and polyhydramnios, two were small for gestational age, and one with small head circumference. Among the six cases who underwent parental origin detection, the microdeletions were de novo in four fetuses and two fetuses were inherited from the parent with normal phenotype. As for six fetuses with distal 1q21.1 microduplication, nasal bone absence or hypoplasia was shown by ultrasound in four cases and no obvious abnormality was found in the other two cases. Parental origin detection was performed in four cases, which found that one case was de novo and the other three cases were inherited from their phenotypically normal parents. After genetic counseling, five families chose to terminate the pregnancies and the remaining nine cases continued the pregnancies to delivery. The last follow-up showed that all of the nine live births grew well, whose ages ranged from seven months to half past five years old. Conclusions:CMA is of great value in prenatal diagnosis of 1q21.1 distal microdeletion/ microduplication. Ones carrying pathogenic CNV may not develop the disease. Combined with ultrasound findings and parental genetic tracing results, individualized genetic counseling and long-term follow-up are of great importance for reasonable guidance in pregnancy outcome and reproduction.

Prenatal diagnosis of Cri-du-chat syndrome: analysis of 11 cases / 中华围产医学杂志

Objective:To investigate the ultrasonographic and genetic features of Cri-du-chat syndrome (CDCS).Methods:In this retrospective study, cases with CDCS diagnosed in Wuxi Maternal and Child Health Care Hospital from 2004 to 2021 and with complete data were reviewed to describe and analyze the maternal serum prenatal screening, non-invasive prenatal testing (NIPT), ultrasound, genetic examination data, and pregnancy outcomes.Results:All cases were diagnosed by karyotype analysis, seven of them were diagnosed prenatally through amniotic fluid, and four were diagnosed after birth through peripheral blood. Five of the seven cases diagnosed prenatally had an abnormal serological screening, including two cases with 5p- indicated by NIPT. Of the 11 cases, prenatal ultrasonography showed cerebellar transverse diameter less than －2 SD in eight cases, including four with cerebellar hypoplasia (CH), two with fetal growth restriction, and two with cranial diameters less than －2 SD. One case was shown with an increased nuchal translucency, accompanying bilateral choroid plexus cysts of the lateral ventricles, and suspected persistent left superior vena cava. No obvious ultrasound abnormality was observed in the remaining two cases. Among the seven cases diagnosed prenatally, excluding one case that refused parental verification, further single nucleotide polymorphism array (SNP array) showed that all six cases inherited the de novo mutations from the parents. The cytogenetic analysis found the breakpoints at 5p13, 5p14, and 5p15 in five, three, and three cases. All seven pregnancies were terminated in the second trimester. Four children diagnosed postnatally presented with CDCS phenotype during the follow-up at three years old. Conclusions:Fetal CDCS should be considered with CH detected by prenatal ultrasonography, though the correlation between CH and CDCS still needs further investigation. Gene mapping with an SNP array is helpful for phenotypic profiling and genetic counseling.

Prenatal diagnosis and postnatal follow-up of 27 cases with 15q11.2 BP1-BP2 microdeletion syndrome / 中华围产医学杂志

Objective:To summarize the prenatal diagnosis and postnatal follow-up of 15q11.2 BP1-BP2 microdeletion syndrome (Burnside-Butler syndrome, BBS), and provide a reference for the management of BBS.Methods:A retrospective analysis was performed on 27 singleton pregnancies with fetal BBS that were prenatally diagnosed by single nucleotide polymorphism(SNP) array of amniotic fluid in Wuxi Maternity and Child Health Care Hospital from January 2017 to September 2021. Prenatal diagnosis indications, serological screening, prenatal ultrasound features, SNP array results, and postnatal growth and development were described and summarized.Results:(1) Of the 27 cases, the indications of prenatal diagnosis in 14 cases were abnormal sonographic findings, including eight cases with increased nuchal translucency, two with cleft lip and palate/alveolar process cleft, one with fetal multiple joint contracture syndrome, one with fetal right diaphragmatic hernia and single umbilical artery, one with suspected fetal duodenal atresia and one with nasal bone absence. Other indications included high risk of Down syndrome by serological screening in six cases, history of adverse pregnancy in six cases, and advanced age in one case. (2) Karyotyping of amniotic fluid in these 27 BBS fetuses showed normal results and SNP array indicated the deletion range of 311.8-855.3 kb. Parental verification of 23 cases confirmed one was a new mutation, seven were inherited from the father and 15 from the mother. (3) Five pregnancies were terminated in the second trimester and the remaining 22 cases were live births. (4) The median follow-up of the 22 children was 1 year 8 months (range 0.5 months to 4 years 3 months), which found low body weight and/or growth retardation in six cases, low body weight with language retardation in one case, low body weight with growth retardation and hyperactive behavior in one case, language retardation with left ear appendage in one case, cleft palate accompanied by duodenum/cleft lip and alveolar cleft in two cases without abnormal development after surgical treatment, and no abnormal growth in the remaining 11 cases.Conclusion:For BBS fetuses, the proportion of ultrasound abnormalities is high but with a low specificity in prenatal diagnosis, and the risk of abnormal postnatal growth and development/behavior is high, which requires continuous monitoring.

Analysis of FGD1 gene variant in a child with Aarskog-Scott syndrome / 中华医学遗传学杂志

OBJECTIVE@#To detect pathogenic variant of the FGD1 gene in a boy with Aarskog-Scott syndrome.@*METHODS@#Genetic variant was detected by high-throughput sequencing. Suspected variant was verified by Sanger sequencing. The nature and impact of the candidate variant were predicted by bioinformatic analysis.@*RESULTS@#The child was found to harbor a novel c.1906C>T hemizygous variant of the FGD1 gene, which has led to conversion of Arginine to Tryptophane at codon 636(p.Arg636Trp). The same variant was found in his mother but not father. Based on the American College of Medical Genetics and Genomics guidelines, the c.1906C>T variant of FGD1 gene was predicted to be likely pathogenic(PM1+PM2+PM5+PP2+PP3+PP4).@*CONCLUSION@#The novel c.1906C>T variant of the FGD1 gene may underlay the Aarskog-Scott syndrome in this child. Above finding has enabled diagnosis for the boy.

Prenatal diagnosis of Jacobsen syndrome in a fetus carried by a pregnant woman with intellectual disability / 中华医学遗传学杂志

OBJECTIVE@#To assess the value of combined cytogenetic and molecular techniques for the prenatal diagnosis of a pregnant woman with intellectual disability (ID).@*METHODS@#The fetus and its parents were subjected to G-banding karyotyping analysis, single nucleotide polymorphism array (SNP-array) and fluorescence in situ hybridization (FISH) analysis.@*RESULTS@#G-banding karyotype analysis revealed that the woman has carried a chromosomal microdeletion 46,XX,del(11)(q24), and the fetus was a carrier of 46,XN,del(11)(q24)mat. Subsequent SNP-array and FISH analysis of the pregnant woman indicated that the microdeletion has mapped to 11q24.1-q25. Both the pregnant woman and her fetus were diagnosed with Jacobsen syndrome.@*CONCLUSION@#Combined use of cytogenetic and molecular genetic techniques can facilitate diagnosis of patients with intellectual disability.

Prenatal diagnosis of a fetus with partial trisomy 8p resulting from a balanced maternal translocation by array-based comparative genomic hybridization / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To determine the karyotype of a fetus with transverse aortic arch hypoplasia, and to investigate the feasibility of array-based comparative genomic hybridization (array-CGH) for molecular genetic diagnosis.</p><p><b>METHODS</b>G-banding was performed to analyze the karyotypes of the fetus and its parents, and array-CGH was applied to identify the chromosomal abnormality of the fetus.</p><p><b>RESULTS</b>G-banding analysis revealed that the pregnant woman has carried a balanced translocation 46,XX, t(8;16)(p21;q24), while the fetus has carried an unbalanced translocation 46,XX,der(16)t(8;16)(p21;q24)mat. Array-CGH analysis suggested that the derivative chromosomal fragment has originated from 8p with breakpoints in 8p23.3-p21.3.</p><p><b>CONCLUSION</b>Trisomy 8p23.3-p21.3 may have predisposed to transverse aortic arch hypoplasia in the fetus. Parental karyotype analysis could help to characterize the translocation and evaluate the recurrent risk. Compared with routine karyotype analysis, aCGH has a higher resolution and greater accuracy for mapping chromosomal aberrations.</p>

Prenatal diagnosis for a women with a suspected birth history of Angelman syndrome / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To verify the diagnosis of Angelman syndrome(AS) in a proband in order to provide prenatal diagnosis for his family.</p><p><b>METHODS</b>Array comparative genome hybridization(array-CGH) and fluorescence in situ hybridization(FISH) on metaphase chromosomes were performed.</p><p><b>RESULTS</b>The karyotype of the proband was normal, and a regional deletion of 15q11.1-11.2 was detected by array-CGH. FISH analysis has confirmed loss of heterozygosity in 15q11.2. No positive results were obtained by array-CGH or karyotype analysis. Amniotic fluid sample was taken from the proband's mother upon her subsequent pregnancy. The karyotype of the fetus was normal, but SNP microarray chip analysis has identified loss of heterozygosity in 8p23.1-p22. As no abnormality was observed by ultrasound and other prenatal examinations, the pregnancy was recommended to continue to full-term, and a healthy infant was born.</p><p><b>CONCLUSION</b>Clinically suspected AS can be diagnosed by array-CGH and FISH. The result may facilitate accurate genetic counseling and prenatal diagnosis for the affected family.</p>

The Inhibitory Effects of 188Re-Labeled Folate Coupling with Magnetic Albumin Nanoparticles on SKOV3 Ovarian Cancer in Vivo / 天津医药

Objective To investigate the effects of isotope labeled folate targeting albumin nanoparticles (188Re-fo-late-CDDP/HAS MNP) on human SKOV3 ovarian cancer cells in vivo. Methods The human SKOV3 ovarian cancer model was established in mice. Sixty-four tumor-bearing mice were randomly divided into eight groups:(A) negative control group, (B) chemotherapy group, (C) radiotherapy alone group, (D) hyperthermia alone group, (E) chemotherapy combined with radio-therapy group, (F) chemotherapy combined with hyperthermia therapy group, (G) radiotherapy combined with hyperthermia therapy group and (H) hyperthermia, chemotherapy and radiotherapy combined treatment group. After treatment, the cell pro-liferation and tumor growth were observed. The inhibitory rate of tumor mass was measured. The histopathological changes of tumor were observed in all groups. Results The quality of tumor was significantly lower in treatment groups than that of control group (P＜0.05). There was the lowest quality of tumor in hyperthermia, chemotherapy and radiotherapy combined treatment group than that of other treatment groups (P＜0.05). Conclusion The combination of magnetic induction hyper-thermia, chemotherapy, targeted radionuclide of radiation exposure can effectively inhibit the growth of ovarian cancer, which has the potential application for ovarian cancer treatment.