Search

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.

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.

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.

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.

BackgroundTrisomy 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 presentationThree pregnant women presenting diverse indications for prenatal diagnosis accepted amniocentesis: increased nuchal translucency (case 2) and high risk of trisomy 21 (case 1 and case 3). Case 1 and case 2 shared similar duplicated locus in the region of 19q13.42, encompassing part NLRP12 gene. Case 2 inherited the chromosomal duplication from the mother with normal phenotypes. Case 3 carried a 1.445Mb 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.ConclusionsThe 19q13.42 microduplications in our study are the smallest fragments compared to previous literature. We delineated 19q duplication cases without structural ultrasound anomalies for the first time, which enriched the prenatal phenotypes of this chromosomal aberration. 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.

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.

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.

Isodicentric Y chromosomes are considered one of the most common structural abnormalities of the Y chromosome. Neocentric marker chromosomes, with neocentromeres, have drawn increasing attention in recent years. The present study reported an azoospermic male with a neocentric isochromosome Yp, neo(Yp), and an isodicentric Yq, idic(Yq). The karyotype was analyzed using G‑banding, chromosome microarray analysis (CMA), and fluorescence in situ hybridization (FISH) with various detection probes, including sex‑determining region on the Y chromosome (SRY) and Y centromeric, applied at the same time. G‑banding initially revealed the karyotype 47,X,i(Y)(q10),+mar. CMA indicated the presence of an extra Y chromosome, seemingly equivalent to 47,XYY males. FISH delineated the existence of two centromeres on the idic(Yq). For the marker chromosome, two SRY signals were detected instead of the Y‑specific centromere signal, and a visual centromere was observed. This indicated the possible existence of a neocentromere in the marker chromosome, located in the connected region in Yp11.2 band. Finally, the patient's karyotype was established as 47,X,idic(Y)(p11.2), neo(Y)(pter→Yp11.2::Yp11.2→pter). The findings suggested that both idic(Yq) and neo(Yp) could be the main causes of the patient's azoospermia, despite the fact that the partial disomy of Ypter to Yp11.2 did not lead to any major malformations. The present study not only improves the understanding of karyotype/phenotype relationships between neocentric marker Y chromosomes and male infertility, but also supports the hypothesis that the combined application of molecular cytogenetic analysis could aid in reliably confirming breakpoints, origins, and the constitution of the marker chromosomes.

Rationale: Chromosomal duplications are associated with a series of genetic disorders. However, chromosome 5q duplications, especially pure 5q35.3 microduplications, have rarely been reported in the literature. Clinical phenotypes usually depend on the region of chromosome duplicated, its size, and loci. Patient concerns: From 2011 to 2017, prenatal amniotic fluid samples were obtained from 6 pregnant women diagnosed with pure 5q35.3 microduplications following different prenatal indications at our center. We followed up the children of these pregnancies and determined their postnatal health conditions. Diagnoses: Cytogenetic studies delineated that all patients had normal karyotypes, except for patient 6 who had 46,XX,inv(9)(p11q13). Single-nucleotide polymorphism array results showed 177–269 kb duplications of 5q35.3 (chr5:178728830–178997692) in these cases. All shared similar localization of ADAMTS2. Interventions: All pregnant women chose to continue the pregnancies. Follow-up analysis showed that the children presented normal physical and growth developments. Outcomes: We described six prenatal cases with similar 5q35.3 duplications involving part of the ADAMTS2 locus with no apparent postnatal phenotypic abnormalities. Lessons: Our research revealed that partial microduplication of ADAMTS2 (chr5:178728830–178997692) might be benign and not correlate with disorders. And there might exist phenotypic diversities of 5q35.3 duplications.

Rationale: Small supernumerary marker chromosomes (sSMCs) can be usually discovered in the patients with mental retardation, infertile couples, and prenatal fetus. We aim to characterize the sSMC and explore the correlation between with sSMC and male infertility. Patient concerns: A 26-year-old Chinese male was referred for infertility consultation in our center after 1 year of regular unprotected coitus and no pregnancy. Diagnosis: Cytogenetic G-banding analysis initially described a mosaic karyotype 47,X,Yqh-,+mar[28]/46,X,Yqh-[22] for the proband, while his father showed a normal karyotype. The chromosome microarray (CMA) analysis showed there existed a duplication of Yp11.32q11.221, a deletion of Yq11.222q12, a duplication of 20p11.1 for the patient. Azoospermia factor (AZF) microdeletion analysis for the patient showed that he presented a de novo AZFb+c deletion. Fluorescence in situ hybridization further confirmed the sSMC was an sSMC(Y) with SRY signal, Y centromere, and Yq deletion. Interventions: The patient would choose artificial reproductive technology to get his offspring according to the genetic counseling. Outcomes: The sSMC in our patient was proved to be an sSMC(Y), derived from Yq deletion. The spermatogenesis failure of the proband might be due to the synthetic action of sSMC(Y) mosaicism and AZFb+c microdeletion. Lessons: It is nearly impossible to detect the chromosomal origin of sSMC through traditional banding techniques. The molecular cytogenetic characterization could be performed for identification of sSMC so that comprehensive genetic counseling would be offered.

Small supernumerary marker chromosomes (sSMCs), equal in size or smaller than chromosome 20 of the same metaphase, can hardly be identified through traditional banding technique. They are usually associated with intelligent disability, growth retardation, and infertility, but the genotype-phenotype correlations are still complicated for their complex origins and constitutions. Herein, we identified a 26-year-old Chinese infertile male who carried a mosaic sSMC and was diagnosed as severe oligospermia. The G-banding analysis initially described his karyotype as mos 47, XY, +mar[32]/46, XY[18]. The chromosomal microarray analysis results showed a 25.5 Mb gain in Yp11.31q11.23 and a 0.15 Mb loss in Yq12. Two SRY signals were discovered in the “seemingly” normal chromosome Y in both cell lines using SRY probe: one normal SRY was located on the distal tip of the short arm of chromosome Y while the other SRY was located on the terminal of long arm in the same chromosome Y. The sSMC(Y) was finally identified as der(Y) (pter ⟶ q11.23) (SRY-). To our knowledge, the chromosomal Y anomalies, SRY gene translocated from der(Y) (pter ⟶ q11.23) to qter of normal chromosome Y, were not reported before. Our findings indicated that the mosaic presence of sSMC(Y) may be the main cause of severe oligospermia although no other apparent abnormalities were observed in the proband. Further research on association between sSMC(Y) and spermatogenesis impairment should be investigated. It is recommended measures of traditional and molecular cytogenetic analysis should be taken to determine the origins and constitutions of sSMC so as to offer more appropriate genetic counseling for the infertile sSMC carriers.

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.

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 27 weeks 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) × 1. 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.

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.

Introduction: The infertile male individuals carrying the Y-autosome translocations are seldom reported in clinic. Herein, we described a severe oligozoospermic male with rare unbalanced Y;3 translocation transmitted through 3 generations. Patient concerns: A 33-year-old Chinese male was referred for infertility consultation in our center after 10 years’ primary infertility. He was diagnosed as severe oligozoospermia according to the semen analysis. Diagnosis: G-banding analysis initially described the karyotype as 46, XY, add (3) (p26) for the patient, and his wife's karyotype was 46, XX. The chromosomal microarray analysis identified 3.81Mb and 0.29Mb duplications in Yq11.223q11.23 and Yq12, separately. No deletions were detected in azoospermia factors (AZF)a, AZFb and AZFc. Fluorescence in situ hybridization analysis further confirmed the existence of sex-determining region Y gene and verified that Yq12 was translocated to the terminal short arm of chromosome 3(3p26). Interventions: The couple chose intracytoplasmic sperm injection to get their offspring. The wife underwent amniocentesis for cytogenetic analysis but suffered termination of pregnancy due to premature rupture of membranes. Outcomes: The karyotype of the patient was finally described as 46, X, der(3)t(Y;3)(q11.22;p26). His father and the aborted fetus showed the same karyotypes as the patient. Conclusion: Our study not only enriched the karyotype-phenotype correlation of Y-autosome translocation, but also strengthened the critical roles of molecular genetic techniques in identifying the chromosomal breakpoints and regions involved.

Trisomy 16q is a rare disorder with severe abnormalities, which always leads to early postnatal mortality. It usually results from a parental translocation, exhibiting 16q duplication associated with another chromosomal deletion. The present study reports on the clinical presentation and molecular cytogenetic results of a small-for-gestational-age infant, consisting of partial trisomy 16q21→qter and monosomy 2p25.3→pter. The proband presented with moderately low birthweight, small anterior fontanelles, prominent forehead, low hairline, telecanthus, flat nasal bridge, choanal atresia, clinodactyly of the fifth fingers, urogenital anomalies, congenital muscular torticollis and congenital laryngomalacia. The last two traits have not previously been reported in any trisomy 16q and monosomy 2p cases. The proband was trisomic for the 16q21→qter chromosomal region with the karyotype 46,XY,der(2)t(2;16)(p25;q21)pat. The chromosomal anomaly was the result of unbalanced segregation of a paternal balanced translocation, 46,XY,t(2;16)(p25;q21). In this case, molecular cytogenetic analysis had a critical role in delineating the proband's clinical phenotype. Although this patient had a 16q21→qter duplication and a 2p25.3→pter deletion, the latter may have had mild phenotypic effects when associated with trisomy 16q. The literature was also reviewed, focusing on cases with the same breakpoints, localizations and clinical features reported in recent years.

Reciprocal translocation is closely associated with male infertility and recurrent miscarriages. Balanced reciprocal translocations associated with reproductive failures are predominantly observed on chromosome 1. Additionally, infertile male patients present a number of breakpoints throughout chromosome 1. A translocation breakpoint might interrupt the structure of an important gene, leading to male infertility. Here, we report the breakpoints on chromosome 1 translocation and the clinical features presented in carriers, to enable informed genetic counseling of these patients. Balanced reciprocal translocations were found in 1.57% of the tested patients. Among 82 patients, 23 patients (28.05%) were carriers of the chromosome 1 translocation: 12 presented pre-gestational infertility with clinical manifestations of azoospermia or oligozoospermia, while 11 patients presented gestational infertility (able to conceive but with a tendency to miscarry or give birth to a stillborn). The breakpoint at 1p22 was predominantly observed in these patients; additionally, breakpoints at 1p31.2, 1p10, and 1q25 were associated with gestational infertility. Breakpoints at 1p13, 1q12, and 1q21 were associated with pre-gestational infertility. These results suggested that breakpoints at 1p32, 1p13, and 1q21 were predominantly associated with pre-gestational infertility, while that at 1q25 was associated with gestational infertility. Chromosome 1 translocation carriers with infertility presenting as azoospermia or oligospermia should be counseled on chromosomal breakpoints and the different molecular technologies available to facilitate reproduction.

Balanced reciprocal translocations are associated with reproductive failure. Some reciprocal translocation carriers exhibit azoospermia or oligozoospermia, and an association exists between these chromosomal abnormalities and recurrent abortion. Previous reports have indicated the involvement of chromosome 7 translocations in male infertility and recurrent miscarriage. A translocation breakpoint can occur within an important gene, interrupting its structure and leading to male infertility. However, clinical characteristics resulting from chromosome 7 translocation breakpoints have not been studied. Here, we report such breakpoints and their associated clinical features, to enable informed genetic counseling of carriers. Balanced reciprocal translocations were found in 1.57% of the tested patients. Among these 82 individuals, 14 (17.07%) carried a chromosome 7 translocation, of which, five presented with pregestational infertility and clinical manifestations of oligozoospermia or necrospermia, while nine presented with gestational infertility (i.e., were able to conceive, but often resulting in miscarriage). Breakpoints at 7q31 and 7q36 were associated with pregestational infertility, whereas those at 7p10, 7q21.2, 7q22, and 7q32 were connected to gestational infertility. However, the breakpoint at 7p15 was associated with both. Chromosome 7 translocation carriers with pregestational or gestational infertility should be counseled on chromosomal breakpoints and the various molecular technologies available for assisted reproduction.

Rationale: Chromosome deletion/duplication has been reported to be associated with mental disability and dysmorphism according to the accumulated research evidence. Patient concerns: A 25-year-old woman underwent amniocentesis for cytogenetic and single-nucleotide polymorphism (SNP) array analysis at 18 weeks of gestation due to the increased Down syndrome risk of 1/13. Diagnoses: The fetal chromosomal analysis revealed a seemingly “normal” chromosomal karyotype, but the SNP array results showed a partial duplication of chromosome 4q34.1q35.2 and a deletion of chromosome 7q34q36.3fluorescence in situ hybridization (FISH) analysis showed that the couple had normal chromosome 4 and 7, whereas there was a partial signal fragment of chromosome 4 attached on the long arm of chromosome 7 for the fetus. Interventions: The couple finally chose to terminate the pregnancy based on the ultrasonic multiple malformations and the abnormal SNP array results. Outcomes: The duplicated/deleted segments of the fetus were de novo. Meanwhile, we consider SHH and XRCC2 as good candidate genes, which may, in part, explain the observed abnormalities for the fetus. Lessons: The combination of SNP array and FISH analysis can give a molecular chromosomal diagnosis, which will offer more clear cytogenetic diagnosis and genetic counseling.