OBJECTIVE: To carry out genetic testing for 3 fetuses with abnormal prenatal screening. METHODS: Fetal ultrasound, karyotype analysis, single nucleotide polymorphism (SNP) array and fluorescence in situ hybridization were performed. RESULTS: Abnormalities of chromosome 22 were found with all 3 fetuses. Fetus 1 harbored a 7.1 Mb deletion in 22q13.2q13.33 region, which involved 54 OMIM genes including SHANK3 and FBLN1. Fetus 2 had a mosaicism karyotype, with 12% of cells harboring a 6.6 Mb deletion in 22q13.31q13.33, covering 48 OMIM genes such as SHANK3 and PPARA, and 5% of cells harboring a 26.1 Mb duplication in 22q11.1q13.2 involving 285 OMIM genes. Fetus 3 carried a tandem duplication of 1.7 Mb in 22q11.1q11.21, which involved 10 OMIM genes including CECR1, CECR2 and ATP6V1E1. No abnormality was found in the three couples by chromosomal karyotyping and SNP array analysis. CONCLUSION The severity of diseases caused by chromosome 22 abnormalities not only depends on the range of the deletion or duplication, but is also closely related to chromosome structure, gene dose and genetic environment. Combined ultrasonography and various genetic testing techniques in prenatal diagnosis can greatly increase the detection rate of genetic diseases with substantial phenotypic variation.
Chromosome Aberrations ; Chromosome Deletion ; Chromosome Disorders ; diagnosis ; genetics ; Chromosomes, Human, Pair 22 ; genetics ; Female ; Fetus ; Genetic Testing ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Pregnancy ; Prenatal Diagnosis ; Transcription Factors ; Ultrasonography, Prenatal

OBJECTIVE: To carry out prenatal diagnosis for a fetus with increased nuchal translucency (NT) and another fetus with non-invasive prenatal testing (NIPT) suggested reduced sex chromosomes by cytogenetic and molecular techniques. METHODS: Chromosomal karyotyping, single nucleotide polymorphism array (SNP-array) and fluorescence in situ hybridization (FISH) were applied for the diagnoses. Peripheral blood samples were also taken from their parents for chromosomal karyotyping and SNP-array analysis. RESULTS: Both fetuses showed a 46,X,+mar/45,X karyotype. SNP-array has detected a 22.0 Mb duplication at Yp11.31q11.223 and a 3.9 Mb microdeletion at Yq11.223q11.23 in fetus 1, and a 16.9 Mb duplication at Yp11.31q11.221 and a 8.1 Mb deletion at Yq11.222q11.23 in fetus 2. The results were confirmed by FISH. The parents of both fetuses were normal by chromosomal karyotyping and SNP-array. CONCLUSION Combined use of various techniques can enable accurate prenatal diagnosis and genetic counseling.

OBJECTIVE: To carry out prenatal diagnosis for a fetus with absent nasal bone by using cytogenetic and molecular techniques. METHODS: Chromosomal karyotyping, single nucleotide polymorphism array (SNP-array) and fluorescence in situ hybridization (FISH) assays were applied for the diagnoses. Peripheral blood samples were also taken from the parents for chromosomal karyotyping and FISH analysis. RESULTS: The fetus was found to have a 46,XX,add(21)(p11.2) karyotype, and SNP-array has revealed a 11.3 Mb duplication at 21q22.12q22.3 (hg19: 36 762 648-48 093 361), which was confirmed by FISH. Both parents were found to be normal by chromosomal karyotyping and FISH analysis. The fetus was ultimately found to have a karyotype of 46,XX,der(21)t(21;21)(p11.2;q22.1), resulting a de novo partial trisomy of 21q22.1. CONCLUSION Combined use of various techniques has enabled accurate prenatal diagnosis and genetic counseling for the fetus.
Female ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Nasal Bone ; Pregnancy ; Prenatal Diagnosis ; Trisomy/genetics*

Objective To investigate the roles of ultrasound,laboratory methods,and genetic diagnostic techniques in screening and diagnosing fetuses with an unbalanced recombination of chromosome 18[rec(18)] due to parental pericentric inversion,and the relationship between rec(18) fetal phenotypes and their recombinant chromosomes.Methods We analyzed two pedigrees with pericentric inversion of chromosome 18 (including the fetuses and their parents) which received prenatal diagnosis and genetic counseling on March 2017 and March 2018 respectively at Xiamen Maternity and Children Health Care Hospital through karyotype analysis,chromosome microarray analysis(CMA) and fluorescence in situ hybridization (FISH).Literatures were retrieved from Scientific Citation Index,PubMed,China National Knowledge Infrastructure(CNKI) and Wanfang Data from 1970 to June 2018.The genetic counseling records,ultrasound and laboratory findings,pregnancy outcomes of families with pericentric inversion of chromosome 18 in this study and the included literatures were reported and analyzed.Results Non-invasive prenatal testing (NIPT) of one case indicated high risk of fetal trisomy 18 at 22 weeks of gestation.And the imaging examination indicated that fetus had interventricular septal defect and micrognathia at 24+2 weeks.Prenatal diagnosis confirmed that the fetal karyotype was 46,XY,rec(1 8)dup(18q) inv(18)(p1 1.32q12.1) pat,which was originated from his father whose karyotype was 46,XY,inv(1 8)(p1 1.32q12.1).In the other case,serum screening testing indicated high risk of fetal trisomy 18 at 12+3 weeks.Imaging examination indicated that fetus had thickened nuchal translucency at 13+3 weeks and bilateral choroid plexus cysts at 15+6 weeks.Prenatal diagnosis confirmed that the fetal karyotype was 46,XY,rec(18)dup(18q)inv(18) (p11.32q12.1) mat,which was originated from his mother whose karyotype was 46,XX,inv(18)(p11.32q12.1).Among the nine fetuses,including seven from five pedigrees reported in the literature retrieved and two from the two pedigrees we reported,seven showed abnormal soft markers or structures in ultrasound and three of the seven pedigrees had high risk of fetal trisomy 18.Conclusions Ultrasound screening is highly sensitive in detecting rec(18) fetuses,yet the association between ultrasound features and fetal karyotypes is not clear.The combination of multiple genetic analysis methods,including karyotype analysis,CMA and FISH,may be conducive to clarifying the types and sources of complex derived chromosomes.

Objective: To explore the clinical significance of a prenatal case with two small supernumerary marker chromosomes (sSMC) through identification of their origins. Methods: G-banding chromosomal karyotyping analysis were carried out on fetal amniotic fluid sample and peripheral blood samples from both patients. Fluorescence in situ hybridization (FISH) and single nucleotide polymorphism-array (SNP-array) were used to analyze the component and size of the sSMCs. Results: The karyotype of the fetus was determined as 47, XX, + mar[53]/48, XX, + 2 mar[31]/46, XX[14]. SNP-array has revealed four copies of chromosome 2q11.1q11.2 with a size of 2.6 Mb and three copies of 10p11.23q11.23 with a size of 20.6 Mb. The results was confirmed by FISH. Conclusion A rare chromosomal abnormality with two sSMCs was identified by combined karyotype analysis, SNP-array and FISH, which provided valuable information for prenatal diagnosis.

OBJECTIVE: To explore the nature of chromosomal abnormality in a fetus with nasal bone dysplasia and clarify its clinical effect. METHODS: Fetal chromosome karyotype was analyzed by G-banding. Single nucleotide polymorphism array (SNP-array) was used to detect the chromosomal copy number variations, and fluorescence in situ hybridization (FISH) was used to verify the result. RESULTS: Fetal karyotype analysis showed an unknown chromosomal fragment in 21q21 region. SNP-array discovered a 7.5 Mb duplication in the 21q22.12q22.3 region. FISH confirmed that the unknown fragment was derived from a 21q22.12q22.3 duplication. CONCLUSION Combined use of karyotype analysis, SNP-array and FISH has clarified the nature of chromosomal abnormality in a fetus with nasal bone dysplasia, which has enabled more accurate prenatal diagnosis and genetic counseling.

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

OBJECTIVETo explore the applications of fluorescence in situ hybridization (FISH) in the diagnosis for the patients with gonadal dysgenesis.

METHODSAfter routine gynecologic examination, ultrasonography and endocrine examination, 5 cases of gonadal dysgenesis and hypogonadism were analyzed by using chromosomal diagnoses including G-banding, Q-banding, multiplex FISH and BAC-FISH analyses.

RESULTSAmong the 5 cases of gonad agenesis patients, 2 were pure gonadal dysgenesis with 46, XY karyotype, 3 were mixed gonadal dysgenesis with mos 45, X/47, XXX; 45, X/46, XY or 46, X, der(Y) karyotype.

CONCLUSIONSex chromosomal abnormalities resulted in gonadal dysgenesis symptoms. Applications of FISH and BAC-FISH analyses can correctly diagnose the sex chromosomal abnormalities for patients with gonad agenesis and provide accurate medical genetic data for clinical diagnosis and therapy.

Adolescent ; Chromosomes, Artificial, Bacterial ; genetics ; Gonadal Dysgenesis ; diagnosis ; genetics ; pathology ; therapy ; Humans ; In Situ Hybridization, Fluorescence ; methods ; Karyotyping ; Male ; Sex Chromosome Aberrations