ABSTRACT
BACKGROUND: Chromosomal 16p11.2 deletions and duplications are genomic disorders which are characterized by neurobehavioral abnormalities, obesity, congenital abnormalities. However, the prenatal phenotypes associated with 16p11.2 copy number variations (CNVs) have not been well characterized. This study aimed to provide an elaborate summary of intrauterine phenotypic features for these genomic disorders. METHODS: Twenty prenatal amniotic fluid samples diagnosed with 16p11.2 microdeletions/microduplications were obtained from pregnant women who opted for invasive prenatal testing. Karyotypic analysis and chromosomal microarray analysis (CMA) were performed in parallel. The pregnancy outcomes and health conditions of all cases after birth were followed up. Meanwhile, we made a pooled analysis of the prenatal phenotypes in the published cases carrying 16p11.2 CNVs. RESULTS: 20 fetuses (20/20,884, 0.10%) with 16p11.2 CNVs were identified: five had 16p11.2 BP2-BP3 deletions, 10 had 16p11.2 BP4-BP5 deletions and five had 16p11.2 BP4-BP5 duplications. Abnormal ultrasound findings were recorded in ten fetuses with 16p11.2 deletions, with various degrees of intrauterine phenotypic features observed. No ultrasound abnormalities were observed in any of the 16p11.2 duplications cases during the pregnancy period. Eleven cases with 16p11.2 deletions terminated their pregnancies. For 16p11.2 duplications, four cases gave birth to healthy neonates except for one case that was lost to follow-up. CONCLUSIONS: Diverse prenatal phenotypes, ranging from normal to abnormal, were observed in cases with 16p11.2 CNVs. For 16p11.2 BP4-BP5 deletions, abnormalities of the vertebral column or ribs and thickened nuchal translucency were the most common structural and non-structural abnormalities, respectively. 16p11.2 BP2-BP3 deletions might be closely associated with fetal growth restriction and single umbilical artery. No characteristic ultrasound findings for 16p11.2 duplications have been observed to date. Given the variable expressivity and incomplete penetrance of 16p11.2 CNVs, long-term follow-up after birth should be conducted for these cases.
Subject(s)
Chromosome Disorders , Chromosome Duplication , Chromosomes, Human, Pair 16 , Fetus , Phenotype , Chromosomes, Human, Pair 16/genetics , Chromosome Disorders/genetics , Chromosome Disorders/pathology , Pregnancy Outcome/genetics , Prenatal Diagnosis , Fetus/abnormalities , Fetus/diagnostic imaging , Ultrasonography , Humans , Pregnancy , Infant, Newborn , Karyotyping , Retrospective StudiesABSTRACT
OBJECTIVE: To carry out preimplantation genetic testing (PGT) for a Chinese pedigree affected with Rett syndrome (RTT). METHODS: A pedigree affected with RTT who had presented at the First Hospital of Jilin University on June 4, 2021 was selected as the study subject. Variant of the MECP2 gene was analyzed by next generation sequencing (NGS) and Sanger sequencing. Direct sequencing was also used to determine the carrier status for the c.925C>T variant of the MECP2 gene in the blastocysts, and Sanger sequencing was used to validate the results. The MECP2 gene and 168 effective single nucleotide polymorphism (SNP) loci within 2 Mb ranges up- and downstream of the gene were used to construct a haplotype for analyzing the variant site in the embryos, and embryos without the variant were subjected to the analysis for chromosomal aneuploidies. RESULTS: PGT analysis revealed that five out of seven blastocysts did not harbor the pathogenic variant. The results of aneuploidy analysis indicated that two out of five blastocysts without the variant were euploid. Following genetic counselling, the couple had opted to transplant the optimal blastocyst. Following clinical pregnancy, prenatal diagnosis showed that the fetus has a normal chromosomal karyotype, and the c.925C>T variant was not detected in the amniotic fluid sample. A healthy girl was born by Cesarean section at full term. CONCLUSION: NGS can attain efficient PGT detection and reduce the risk of disease recurrence in families affected with RTT.
Subject(s)
Genetic Testing , Pedigree , Preimplantation Diagnosis , Rett Syndrome , Adult , Female , Humans , Pregnancy , East Asian People/genetics , Genetic Testing/methods , High-Throughput Nucleotide Sequencing , Methyl-CpG-Binding Protein 2/genetics , Polymorphism, Single Nucleotide , Rett Syndrome/geneticsABSTRACT
INTRODUCTION: Pure duplication of chromosome 18p is rare, with clinical phenotypes ranging from normal or slight abnormalities to various degrees of mental retardation. It remains difficult to establish a clear genotype-phenotype correlation. METHODS: Chromosomal karyotyping analysis was performed on cultured amniotic fluid cells from three cases. Single nucleotide polymorphism (SNP) array analysis was carried out using the Illumina Human CytoSNP-12 BeadChip. We also carried out a review of the literature regarding 18p11 microduplication. RESULTS: G-banding analysis showed that the three cases had normal karyotypes. SNP array results showed 0.48- to 1.6-Mb microduplications of 18p11.31-p11.22 (chr18: 6995739-8713088) in these cases, encompassing different degrees of LAMA1 duplication. Follow-up analysis showed that the parents of both cases 1 and 2 chose termination of pregnancy. Case 3 presented with normal growth and physical development. Currently, there is not enough evidence supporting the pathogenicity of LAMA1 triplosensitivity. CONCLUSION: We described three prenatal cases with 18p11.31-p11.22 microduplications involving part of the LAMA1 locus. There might be phenotypic diversity associated with 18p11.31-p11.22 microduplications. To avoid unnecessary abortions for pregnancies such as these, comprehensive genetic counseling should be offered.
Subject(s)
Amniocentesis , Chromosome Duplication , Chromosomes, Human, Pair 18 , Female , Humans , Male , Oligonucleotide Array Sequence Analysis , Phenotype , Polymorphism, Single Nucleotide , PregnancyABSTRACT
BACKGROUND: Chromosome 18p deletion syndrome is caused by total or partial deletion of the short arm of chromosome 18 and associated with cognitive impairment, growth retardation and mild facial dysmorphism. However, most studies on the genotype-phenotype correlations in the 18p region are diagnosed postnatally. Prenatal reports involving 18p deletions are limited. METHODS: Three pregnant women opted for invasive prenatal testing due to noninvasive prenatal testing indicating high risk for chromosome 18 abnormalities. Karyotypic analysis and chromosomal microarray analysis (CMA) were performed simultaneously. The pregnancy outcomes for all cases were followed up. Meanwhile, we also made a literature review on prenatal phenotypes of 18p deletions. RESULTS: G-banding analysis showed that 2 fetuses presented abnormal karyotypes: 45,XN,der(18)t(18;21)(p11; q11),-21 (case 2) and 46,XN,18p- (case 3). The karyotype of case 1 was normal. Meanwhile, CMA detected 4.37 Mb (case 1), 7.26 Mb (case 2) and 14.97 Mb (case 3) deletions in chromosome 18p region. All 3 pregnancies were terminated finally according to genetic counseling based upon abnormal CMA results. CONCLUSION: Prenatal diagnosis of 18p deletion syndrome is full of challenges due to the phenotypic diversity, incomplete penetrance and lack of prenatal phenotypes. Increased nuchal translucency and holoprosencephaly are common prenatal phenotypes of distal 18p deletion. For fetuses carrying 18p deletions with atypical sonographic phenotypes, noninvasive prenatal testing could be adopted as an effective approach.
Subject(s)
Chromosome Deletion , Chromosome Disorders , Chromosomes, Human, Pair 18 , Microarray Analysis , Prenatal Diagnosis , Humans , Female , Chromosomes, Human, Pair 18/genetics , Pregnancy , Microarray Analysis/methods , Prenatal Diagnosis/methods , Adult , Chromosome Disorders/diagnosis , Chromosome Disorders/genetics , Karyotyping/methodsABSTRACT
Objective: Genetic etiology plays a critical role in fetal ventriculomegaly (VM). However, the studies on chromosomal copy number variants (CNVs) in fetal VM are limited. This study aimed to investigate the chromosomal CNVs in fetuses with mild to moderate VM, and explore its genotype-phenotype correlation. Methods: A total of 242 fetuses with mild to moderate VM detected by prenatal ultrasound were enrolled in our study from October 2018 to October 2022. All cases underwent chromosomal microarray analysis (CMA) and G-banding simultaneously. All VM cases were classified different subgroups according to the maternal age, severity, VM distribution and presence/absence of other ultrasound abnormalities. The pregnancy outcomes and health conditions after birth were followed up. We also performed a pooled analysis regarding likely pathogenic and pathogenic CNVs (LP/P CNVs) for VM. Results: The detection rate of chromosomal abnormalities by karyotyping was 9.1% (22/242), whereas it was 16.5% (40/242) when CMA was conducted (P < 0.05). The total detection rate of chromosomal abnormalities by karyotyping and CMA was 21.1% (51/242). A 12.0% incremental yield of CMA over karyotyping was observed. The detection rate of total genetic variants in fetuses with bilateral VM was significantly higher than in fetuses with unilateral VM (30.0% vs. 16.7%, P = 0.017). No significant differences were discovered between isolated VM and non-isolated VM, or between mild and moderate VM, or between advanced maternal age (AMA) and non-AMA (all P > 0.05). 28 fetuses with VM were terminated and 214 fetuses were delivered: one presented developmental delay and one presented congenital heart disease. The VM cases with both positive CMA and karyotypic results had a higher rate of termination of pregnancy than those with either a positive CMA or karyotypic result, or both negative testing results (P < 0.001). Conclusion: The combination of CMA and karyotyping should be adopted to improve the positive detection rate of chromosomal abnormalities for VM. The total genetic abnormalities detected using both techniques would affect the final pregnancy outcomes. LP/P CNVs at 16p11.2, 17p13, and 22q11.21 were identified as the top three chromosomal hotspots associated with VM, which would enable genetic counselors to provide more precise genetic counseling for VM pregnancies.
ABSTRACT
RATIONALE: Chromosome microdeletions within 7q11.23 can result in Williams-Beuren syndrome which is a rare autosomal dominant disorder. Williams-Beuren syndrome is usually associated with developmental delay, cardiovascular anomalies, mental retardation, and characteristic facial appearance. PATIENT CONCERNS: Two pregnant women underwent amniocentesis for cytogenetic analysis and chromosomal microarray analysis (CMA) because of abnormal ultrasound findings. Case 1 presented subependymal cyst and case 2 presented intrauterine growth restriction, persistent left superior vena cava and pericardial effusion in clinical ultrasound examination. DIAGNOSES: Cytogenetic examination showed that the 2 fetuses presented normal karyotypic results. CMA detected 1.536 Mb (case 1) and 1.409 Mb (case 2) microdeletions in the region of 7q11.23 separately. INTERVENTIONS: Both couples opted for the termination of pregnancies based upon genetic counseling. OUTCOMES: The deleted region in both fetuses overlapped with Williams-Beuren syndrome. To our knowledge, case 1 was the first reported fetus of Williams-Beuren syndrome with subependymal cyst. LESSONS: The genotype-phenotype of Williams-Beuren syndrome is complicated due to the phenotypic diversity. For prenatal cases, clinicians should consider the combination of ultrasonography, traditional cytogenetic, and molecular diagnosis technology when genetic counseling.
Subject(s)
Cysts , Williams Syndrome , Humans , Female , Pregnancy , Williams Syndrome/diagnosis , Williams Syndrome/genetics , Vena Cava, Superior , Prenatal Diagnosis , Genetic TestingABSTRACT
Objective: Chromosomal 1q21.1 deletions and duplications are genomic disorders that are usually diagnosed postnatally. However, the genotype-phenotype correlations of 1q21.1 copy number variants (CNVs) during the prenatal period are still not clear. This study aimed to provide a systematic summary of prenatal phenotypes for such genomic disorders. Methods: In total, 26 prenatal amniotic fluid samples diagnosed with 1q21.1 microdeletions/microduplications were obtained from pregnant women who opted for invasive prenatal testing. Karyotypic analysis and chromosomal microarray analysis (CMA) were performed for all cases simultaneously. The pregnancy outcomes and health conditions after birth in all cases were followed up. Meanwhile, prenatal cases with 1q21.1 microdeletions or microduplications in the literature were retrospectively collected. Results: In total, 11 pregnancies (11/8,252, 0.13%) with 1q21.1 microdeletions and 15 (15/8,252, 0.18%) with 1q21.1 microduplications were identified. Among these 1q21.1 CNVs, 4 cases covered the thrombocytopenia-absent radius (TAR) region, 16 cases covered the 1q21.1 recurrent microdeletion/microduplication region, and 6 cases covered all regions mentioned above. The prenatal abnormal ultrasound findings were recorded in four participants with 1q21.1 deletions and seven participants with 1q21.1 duplications. Finally, three cases with 1q21.1 deletions and five with 1q21.1 duplications terminated their pregnancies. Conclusion: In the prenatal setting, 1q21.1 microdeletions were associated with increased nuchal translucency (NT), anomalies of the urinary system, and cardiovascular abnormalities, while 1q21.1 microduplications were correlated with cardiovascular malformations, nasal bone dysplasia, and increased NT. In addition, cerebral ventriculomegaly might be correlated with 1q21.1 microduplications. Considering the variable expressivity and incomplete penetrance of 1q21.1 CNVs, long-term follow-up after birth should be carried out in these cases.
ABSTRACT
Rotundic acid (RA, 1), a natural compound, exhibits potent tumor cell growth inhibiting properties. To date there are no reports on derivatives of RA. Furthermore, the 28-COOH position of RA might make it unstable and induced serious gastrointestinal side effects when it was applied in vivo. Therefore, in order to explore and make use of this compound, eight new amino acid derivatives of RA at the 28-COOH position were synthesized and evaluated for their cytotoxicities in vitro on three tumor cell lines including A375, HepG2 and NCI-H446. As a result, a few of these new amino acid derivatives showed stronger cytotoxicity. Compound 5a was found to have the best inhibition activity on the three tested human tumor cell lines with IC(50) values of less than 10 µM compared with RA treatment. Meanwhile, the cytotoxicity of compound 6b was significantly higher than that of RA on the A375 cell line and almost the same as RA on the HepG2 and NCI-H446 cell lines. Hence, compounds 5a and 6b may serve as potential lead compounds for the development of new anti-tumor drugs.
Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Triterpenes/chemical synthesis , Triterpenes/pharmacology , Antineoplastic Agents/chemistry , Cell Line, Tumor , Drug Screening Assays, Antitumor , Humans , Inhibitory Concentration 50 , Triterpenes/chemistryABSTRACT
ABSTRACT: Trisomy 6q is a recognizable syndrome which exhibits psychomotor/growth retardation, developmental/intellectual disabilities, feeding difficulties, facial dysmorphism, hearing loss, brain and heart malformations. The purpose of this study was to delineate the prenatal features of proximal 6q14.1 duplication in fetal period, which was rarely reported in clinic. Eight pregnant women who opted for amniocentesis due to the fetal ultrasound abnormalities, maternal serum screening or other indications for prenatal diagnosis between 2019 and 2020. Chromosomal microarray analysis and G-banding analysis were offered after informed consents were obtained. Cytogenetic prenatal investigation showed all fetuses presented normal karyotypes except case 4 exhibiting a balanced chromosomal translocation 46,XX,t (4;8)(p16;q24). The chromosomal microarray analysis detected 0.211-0.242 Mb duplications of 6q14.1 (chr6: 80109532-80351666, hg19) in all 8 cases, encompassing the morbid gene LCA5 in common. Seven pregnant women (P1-P7) continued their pregnancies and delivered healthy infants at term while the parents of case 8 opted for termination of pregnancy for severe abnormal ultrasound findings. Overall, all neonates were in a good healthy condition with no evident anomalies, ranging from 2 m to 16 m. It is proposed that 6q14.1 duplication involving LCA5 gene detected in our study might be variants of likely benign. However, further large-scale studies should be gathered to assess its pathogenicity. To our knowledge, our study is the first report focusing on prenatally detected proximal 6q14.1 duplication, accompanied by detailed clinic phenotypes. Diverse ultrasound findings were observed in these cases, ranging from normal to abnormal. More evidence should be gathered to interpret the prenatal genotype-phenotype correlation of 6q14.1 duplication. For these cases with 6q14.1 microduplication, long term follow up should be carried out in case abnormal clinical symptoms or developmental-behavioral disorders emerge.
Subject(s)
Prenatal Diagnosis , Trisomy , Amniocentesis , Female , Humans , Microarray Analysis , Phenotype , Pregnancy , Trisomy/diagnosis , Trisomy/genetics , Ultrasonography, PrenatalABSTRACT
OBJECTIVE: Chromosome 16p11.2 deletions have been recognized as a genetic disorder with well-described postnatal phenotypes. However, the prenatal manifestations are atypical for lacking of enough evidence. CASE REPORT: Four pregnant women underwent amniocentesis for cytogenetic analysis and chromosomal microarray analysis (CMA) because of various indications for prenatal diagnosis: prenatal ultrasound abnormalities (cases 1, 2 and 4) and the childbearing history of cerebral palsy child (case 3). No overlapping phenotypes were observed in cases 1, 2 and 4, which might indicate phenotypic diversities in prenatal phenotypes for 16p11.2 microdeletion. All four fetuses showed normal karyotypic results while CMA identified 0.303-0.916 Mb microdeletions of 16p11.2, encompassing BP2-BP3 and BP4-BP5 regions separately. According to the parental CMA verification, case 1 carried a maternal inherited duplication in the region of Xp22.33 and a de novo deletion in the region of Xp21.1. All parents opted for the termination of pregnancies based upon genetic counselling. CONCLUSION: Our findings enriched the intrauterine phenotypic features of 16p11.2 microdeletions, which would be beneficial for genetic counselling in clinic. In addition, preimplantation genetic testing was recognized as a first-tier approach for such carriers if they intended to conceive again.
Subject(s)
Amniocentesis , Chromosome Deletion , Cytogenetic Analysis , Female , Genetic Testing , Humans , Phenotype , Pregnancy , Prenatal DiagnosisABSTRACT
OBJECTIVE: We report a prenatal case of male fetus with a 2q13 deletion and an Xq27.3q28 duplication, presenting nasal bone dysplasia by ultrasound examination. And we compare the similarities of clinical features of cases consisting of similar 2q deletion and Xq duplication. CASE REPORT: A 30-year-old woman was referred for prenatal diagnosis and genetic counseling at 24 weeks of gestation. Prenatal ultrasound showed nasal bone dysplasia of the fetus. Amniocentesis revealed the karyotype of the fetus as 46, XY and the results of chromosomal microarray analysis was arr[GRCh37] 2q13(110467258-111370025)x1, arr[GRCh37]Xq27.3q28(144050780-149748782)x2. The parents both have normal karyotypes. The couple chose to continue the pregnancy and finally delivered a male infant at 39 weeks of gestation. His weight was 2850 g and length was 50 cm. Physical examination of the newborn revealed no apparent anomalies. Until the boy was one year old, there was no abnormalities in his growth and development. The long-term follow-up till adulthood for the healthy infant is necessary. CONCLUSION: The development of CMA plays a critical role in prenatal diagnosis and genetic counseling for unidentified chromosomal anomalies. More clinical information and further studies of patients with these anomalies will identify the pathogenicity of the involving genes and improve the understanding of the phenotype-genotype correlation.
Subject(s)
Amniocentesis , Bone Diseases, Developmental/diagnostic imaging , Chromosome Deletion , Chromosome Duplication , Prenatal Diagnosis/methods , Adult , Comparative Genomic Hybridization , Cytogenetic Analysis , Female , Humans , Infant , Karyotype , Karyotyping , Male , Pregnancy , Ultrasonography, PrenatalABSTRACT
OBJECTIVE: We present prenatal diagnosis and molecular cytogenetic characterization of a chromosome 1q42.3q44 deletion and 8q24.3 duplication in a fetus with single umbilical artery and ventricular septal defects, and we discuss the genotype-phenotype correlation. CASE REPORT: Here, we describe a fetus with abnormal sonography findings showing a single umbilical artery and ventricular septal defects. Conventional karyotyping initially described the fetus as 46,XX,1q? and molecular cytogenetic analysis (CMA) revealed a 13-Mb deletion and 4.6-Mb duplication of regions 1q42.3q44 and 8q24.3, respectively. The father's karyotype was 46,XY. The mother's karyotype was 46,XX,t(1;8)(q42;q24). Therefore, the karyotype of the fetus was identified as 46,XX,der(1)t(1;8)(q42;q24) mat. After genetic counseling, the couple chose to terminate the pregnancy. We suggest that the ACTN2, RYR2 and PUF60 genes may be responsible for the ultrasound abnormalities observed in the fetus. CONCLUSION: To the best of our knowledge, this is the first report of a 1q deletion and 8q duplication identified by prenatal detection. The application of karyotype analysis and CMA provides more accurate characterization for unidentified chromosomal anomalies, and benefits appropriate genetic counseling in the clinic.
Subject(s)
Cytogenetic Analysis/methods , Heart Septal Defects, Ventricular/genetics , Prenatal Diagnosis/methods , Single Umbilical Artery/genetics , Adult , Chromosome Aberrations , Chromosome Deletion , Female , Fetus , Heart Septal Defects, Ventricular/diagnostic imaging , Humans , Karyotyping , PregnancyABSTRACT
BACKGROUND: Trisomy 19q is a recognizable syndrome and associated with a wide spectrum of clinical phenotypes in clinic. The purpose of this study was to explore the prenatal phenotypes of 19q13.42 duplication, which was rarely reported in clinic. CASE PRESENTATION: Three pregnant women presenting diverse indications for prenatal diagnosis accepted amniocentesis: increased nuchal translucency and fetal pyelic separation (case 2) and high risk of maternal serum screening for Down syndrome (case 1 and case 3). Case 1 and case 2 shared similar duplicated locus in the region of 19q13.42, encompassing part NLRP12 gene. The latter inherited the chromosomal duplication from the mother with normal phenotypes. Case 3 carried a 1.445 Mb duplication in the 19q13.42q13.43 region. It was proposed that evolutionary duplication of NLRP12 gene could have a causative role in autoinflammatory diseases development. The genotype-phenotype correlation depends mainly on the duplicated size and functional genes involved, which is still yet to be determined. All pregnant women chose to continue the pregnancy and delivered healthy children with no apparent abnormalities. CONCLUSIONS: The 19q13.42 microduplications in our study were the smallest fragments compared to previous literature. Our findings enriched the prenatal phenotypes for this chromosomal microscopic imbalance. It was proposed that long term follow up analysis should be guaranteed till adulthood to determine whether there will be other emerging clinical symptoms and developmental-behavioral disorders for such carriers.
ABSTRACT
ABSTRACT: Trisomy 9p is one of the most common chromosomal partial trisomies in newborns. However, reports on prenatal 9p microduplications are rare in the clinic. This study aimed to examine the genotype-phenotype correlation and assess the clinical significance of 9p24.3 microduplication encompassing the DOCK8 gene. Eight pregnant women underwent amniocentesis for cytogenetic and genetic testing for various indications for prenatal diagnosis from January 2019 to January 2020. Chromosomal karyotypic analysis was performed on G-band metaphases that were prepared from cultured amniotic fluid cells. Chromosomal microarray analysis was carried out to detect chromosomal copy number variations. We also performed a literature review on clinical data on similar 9p24.3 microduplications to determine the genotype-phenotype correlation. We detected 123-248-kb microduplications in the region of 9p24.3 (chr9: 208454-469022), involving part of or the entire DOCK8 gene. The indications for prenatal diagnosis mainly focused on the risk of maternal serum screening for trisomy 21/18, advanced maternal age, and increased nuchal translucency. No evident structural abnormalities were observed for all fetuses, except for case 5 who presented with increased nuchal translucency in prenatal ultrasound findings. Follow-up of postnatal health was performed and showed no apparent abnormalities for cases 1 to 6 after birth. The parents of case 7 chose to terminate the pregnancy while the parents of case 8 chose to continue the pregnancy. We propose that 9p24.3 microduplications that encompass part of or the entire DOCK8 gene are variants that might be benign. However, further large-scale studies are necessary to evaluate the clinical pathogenicity. For prenatal cases with 9p24.3 microduplication, postnatal health and growth should be followed up and assessed regularly from childhood to adulthood.
Subject(s)
Guanine Nucleotide Exchange Factors/genetics , Prenatal Diagnosis/methods , Adult , Amniotic Fluid , Chromosomes, Human, Pair 9/physiology , DNA Copy Number Variations , Female , Guanine Nucleotide Exchange Factors/analysis , Humans , Pregnancy , Trisomy/physiopathologyABSTRACT
RATIONALE: Chromosomal 3q deletion is a recurrent genomic alternation, which is rarely reported in clinic. PATIENT CONCERNS: A 27-year-old woman underwent amniocentesis for cytogenetic analysis and single nucleotide polymorphism (SNP) array analysis at 27âweeks of gestation, due to ventricular septum defect in prenatal ultrasound findings. DIAGNOSES: G-banding analysis showed the karyotype of the fetus was normal and the couple also had normal karyotypes. However, SNP array detected a 1.71 Mb microdelection in 3q29, which was described as arr[hg19]3q29(194184392-195887205)â×â1. There are 12 genes located in this locus. INTERVENTIONS: The couple refused SNP array to testify the 3q29 microdeletion was inherited or de novo and they chose termination of pregnancy. OUTCOMES: The deleted region in the fetus overlapped with part 3q29 microdeletion syndrome, which was characterized by learning disability, speech delay, mental deficiency, ocular abnormalities and craniofacial features. In addition, no similar/overlapping 3q29 microdeletion cases were reported according to the published literature and database. LESSONS: For the chromosomal microscopic imbalances partially overlapping with the defined pathogenic syndrome, deleted/duplicated size, genetic materials and phenotypic diversity should be taken into consideration when genetic counseling is offered by the clinicians.
Subject(s)
Heart Septal Defects, Ventricular/diagnostic imaging , Intellectual Disability/diagnosis , Ultrasonography, Prenatal , Adult , Amniocentesis , Chromosome Deletion , Chromosomes, Human, Pair 3/genetics , Developmental Disabilities/diagnosis , Developmental Disabilities/genetics , Diagnosis, Differential , Female , Genetic Counseling , Heart Defects, Congenital , Heart Septal Defects, Ventricular/genetics , Humans , Intellectual Disability/genetics , Pregnancy , Pregnancy Trimester, SecondABSTRACT
RATIONALE: 1q21.1 duplication is an uncommon chromosomal submicroscopic imbalance which is associated with growth/mental retardation, dysmorphic features, autism, multiple congenital and neuropsychiatric disorders. PATIENT CONCERNS: Two pregnant women underwent amniocentesis for cytogenetic analysis and chromosomal microarray analysis (CMA) following abnormal ultrasound findings. Case 1 presented short nasal bone and case 2 showed absent nasal bone, ventricular septal defect and umbilical cord circling in ultrasonic examination. DIAGNOSES: G-banding analysis showed that the two fetuses presented normal karyotypic results while CMA detected 1.796 Mb (case 1) and 1.242 Mb (case 2) microduplications in the region of 1q21.1q21.2 separately. Furthermore, the CMA also revealed a 1.2 Mb microdeletion of 8p23.3 in case 1. INTERVENTIONS: The couple in case 1 chose to terminate the pregnancy, while the couple in case 2 continued the pregnancy and finally delivered a male infant who presented low nasal bridge and ventricular septal defect. OUTCOMES: The 1q21.1q21.2 duplications in our report were located in the distal 1q21.1 region, overlapping with 1q21.1 duplication syndrome. Case 2 was the first reported live birth with 1q21.1 duplication according to prenatal CMA detection in China. LESSONS: The genotype-phenotype of 1q21.1 duplication is complicated due to the phenotypic diversity, incomplete penetrance, and lack of obvious characteristics. So it is difficult to predict the postnatal development and health conditions clinically. Hence, long term follow up is necessary for newborn infants with 1q21.1 duplication, irrespective of whether the duplication is de novo or inherited.
Subject(s)
Chromosome Deletion , Heart Septal Defects, Ventricular/diagnostic imaging , Ultrasonography, Prenatal , Abnormalities, Multiple , Adult , Female , Genetic Counseling , Heart Septal Defects, Ventricular/genetics , Humans , Infant, Newborn , Male , Pregnancy , Pregnancy Trimester, Second , Young AdultABSTRACT
RATIONALE: 15q11.2 microdeletion syndrome is a relatively rare chromosomal abnormality with incomplete penetrance and phenotypic variability. The reports on prenatal ultrasound abnormalities of fetus with 15q11.2 microdeletion are rare. PATIENT CONCERNS: A 30-year-old woman was referred for genetic counseling and prenatal diagnosis at 19 weeks of gestation because of increased nuchal translucency in prenatal ultrasound findings and a history of spontaneous abortion. DIAGNOSES: The cytogenetic analysis showed the karyotype of the fetus was 46,XY, inv(4)(p15q31) and chromosomal microarray analysis detected a 0.512 Mb deletion in 15q11.2 region. We recalled the parents to determine the origination of these chromosomal abnormalities. INTERVENTIONS: The pregnant woman chose to continue the pregnancies and finally delivered a healthy male infant at 39 weeks. OUTCOMES: The fetus inherited the inv(4)(p15q31) from his mother while the deletion in 15q11.2 was identified as de novo. Given the normal phenotype of the mother, it was reasonable to assume that the maternal inherited inv(4) in the fetus would not increase the risk of his abnormal phenotype. However, the pathogenicity of the microdeletion in 15q11.2 for the infant is unknown and long-term follow-up of progeny should be paid more attention. LESSONS: The combined application of traditional banding technique and molecular cytogenetic techniques can not only detect chromosomal structural abnormalities, but also identify the subchromosomal imbalances, which is beneficial to genetic counselling and would offer more guidance to prenatal diagnosis.
Subject(s)
Intellectual Disability/diagnosis , Prenatal Diagnosis/methods , Adult , Chromosome Aberrations , Chromosomes, Human, Pair 15 , Female , Genetic Counseling , Humans , Karyotyping , Nuchal Translucency Measurement , PregnancyABSTRACT
Chromosomal rearrangements, such as duplications/deletions, can lead to a variety of genetic disorders. Herein, we reported a prenatal case with right aortic arch and aberrant left subclavian artery, consisting of a complex chromosomal copy number variations. Routine cytogenetic analysis described the chromosomal karyotype as 46,XY, add (2)(q37) for the fetus. However, the chromosomal microarray analysis (CMA) identified a 22.4 Mb duplication in chromosome 4p16.3p15.2, a 3.96 Mb microduplication in 12p11.1q11, and a 1.68 Mb microdeletion in Xp22.31. Fluorescence in situ hybridization (FISH) using a chromosome 4 painting probe was found to hybridize to the terminal of chromosome 2q on the fetus, thus confirming that the extra genetic materials of chromosome 2 was actually trisomy 4p detected through CMA. Meanwhile, the parental karyotypes were normal, which proved that the add (2) was de novo for fetus. The duplication of Wolf-Hirschhorn syndrome critical region (WHSCR) and X-linked recessive ichthyosis associated with Xp22.31 deletion separately were considered potentially pathogenic causes although other abnormalities involving these syndromes were not observed. For prenatal cases, the combined utilization of ultrasonography, traditional cytogenetic, and molecular diagnosis technology will enhance better diagnostic benefits, offer more detailed genetic counselling, and assess the prognosis of the fetuses.
Subject(s)
Chromosome Aberrations , DNA Copy Number Variations/genetics , Prenatal Diagnosis , Adult , Cytogenetic Analysis , Female , Fetus/diagnostic imaging , Fetus/pathology , Humans , Pregnancy , Trisomy/genetics , Ultrasonography, Prenatal , Vascular Ring/diagnostic imaging , Vascular Ring/pathology , Young AdultABSTRACT
RATIONALE: Intracranial aneurysm with the first manifestation of acute subdural hematoma (aSDH) is rare in the field of neurosurgery. Usually subarachnoid hemorrhage or intracranial hematoma happens after the rupture of an intracranial aneurysm, whereas trauma is the primary cause of aSDH. PATIENT CONCERNS: Here, we present the case of a 71-year-old woman who presented with spontaneous aSDH with progressive headache and vomiting. DIAGNOSIS: Urgent head computed tomography (CT) identified an aSHD, but the patient had no history of trauma. CT angiography (CTA) identified the cause of the aSDH as rupture of an intracranial aneurysm in the left middle cerebral artery. INTERVENTIONS: Emergent craniotomy with hematoma evacuation was performed. OUTCOMES: Due to prompt diagnosis and appropriate intervention, the patient recovered fully with no disability. LESSONS: This unique case demonstrates that aSDH caused by intracranial aneurysm rupture requires timely identification and appropriate action to prevent adverse outcomes. We performed a comprehensive systematic literature review to examine the etiology and pathogenesis of non-traumatic aSDH. Furthermore, digital subtraction angiography should be considered in patients diagnosed with an aSDH with no known cause.