We present prenatal diagnosis of maternal uniparental disomy (UPD) 21 in association with low-level mosaic trisomy 21 at amniocentesis in a pregnancy associated with intrauterine growth restriction (IUGR) and a favorable outcome.A 42-year-old, gravida 2, para 0, woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis initially revealed a karyotype of 46,XX in 20/20 colonies of cultured amniocytes. Simultaneous array comparative genomic hybridization (aCGH) analysis on uncultured amniocytes revealed a result of arr [GRCh37] (21) × 3 [0.16], (X) × 2, compatible with mosaic trisomy 21. After extensive investigation, the final result of conventional cytogenetic analysis of cultured amniocytes was 47,XX,+21[1]/46,XX[40]. The parental karyotypes were normal. Repeat amniocentesis was performed at 21 weeks of gestation. The cultured amniocytes had a karyotype of 47,XX,+21[3]/46,XX[27] and the uncultured amniocytes had a mosaic trisomy 21 level of 8.8% (10/114 cells) by interphase fluorescence in situ hybridization (FISH), a mosaic trisomy 21 level of 10% (log2 ratio = 0.08) by aCGH, and maternal UPD 21 by polymorphic DNA marker analysis. Prenatal ultrasound revealed IUGR. At 38 weeks of gestation, a phenotypically normal 2695-g baby was delivered. The cord blood and umbilical cord had the karyotype of 46,XX and maternal UPD 21. The placenta had a karyotype of 47,XX,+21[8]/46,XX[32] and a maternal origin of trisomy 21. Postnatal FISH analysis on 101 buccal mucosal cells showed 6.9% (7/101 cells) mosaicism compared with 2% (2/100 cells) in the normal control. The baby was doing well at age four months.Pregnancy with low-level mosaic trisomy 21 and maternal UPD 21 at amniocentesis can be associated with IUGR and a favorable outcome. Fetuses with maternal UPD 21 can be associated with mosaic trisomy 21 at amniocentesis. 

Prenatal diagnosis of maternal uniparental disomy 21 in association with low-level mosaic trisomy 21 at amniocentesis in a pregnancy associated with intrauterine growth restriction and a favorable outcome.

Objective We present perinatal molecular cytogenetic analysis of low-level mosaicism for trisomy 21 in a pregnancy with maternal uniparental disomy (UPD) of chromosome 21 in the fetus. Case report A 39-year-old woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 47,XX,+21[6]/46,XX[25]. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed arr (21) × 2–3, (X) × 2 with about 18% gene dosage increase in chromosome 21 consistent with mosaic trisomy 21. Cordocentesis was performed at 20 weeks of gestation, and the cord blood lymphocytes had a karyotype of 47,XX,+21[3]/46,XX[72]. Prenatal ultrasound findings were unremarkable. After genetic counseling, the parents decided to continue the pregnancy. At 39 weeks of gestation, a 3,494-g phenotypically normal female baby was delivered without phenotypic features of Down syndrome. There was no dysplasia of middle phalanx of the fifth fingers of both hands. The cord blood had a karyotype of 47,XX,+21[2]/46,XX[48]. The placenta had a karyotype of 47,XX,+21[37]/46,XX[3]. The umbilical cord had a karyotype of 47,XX,+21[1]/46,XX[39]. aCGH analysis on the DNA extracted from cord blood revealed no genomic imbalance. Polymorphic DNA marker analysis on the DNAs extracted from cord blood and parental bloods revealed maternal uniparental heterodisomy 21 in the baby. Interphase fluorescence in situ hybridization analysis on buccal mucosal cells revealed trisomy 21 signals in 15/101 (14.9%) buccal cells at birth and in 1/122 (0.82%) buccal cells at age 45 days. Conclusion Low-level mosaicism for trisomy 21 at amniocentesis associated with maternal UPD 21 in the fetus can have a favorable outcome.

Prenatal diagnosis of low-level mosaicism for trisomy 21 by amniocentesis in a pregnancy associated with maternal uniparental disomy of chromosome 21 in the fetus and a favorable outcome.

Objective We present perinatal cytogenetic discrepancy in a fetus with low-level mosaicism for trisomy 21 and a favorable outcome. Case report A 40-year-old woman underwent amniocentesis at 19 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 47,XY,+21[7]/46,XY[14]. She underwent cordocentesis 21 weeks of gestation, and the karyotype of cord blood was 47,XY,+21[13]/46,XY[38]. The prenatal ultrasound findings were unremarkable. After genetic counseling of a favorable outcome of low-level mosaic trisomy 21 at amniocentesis, the parents decided to continue the pregnancy, and a 3128-g phenotypically normal male baby was delivered at 38 weeks of gestation without phenotypic features of Down syndrome. Postnatal cytogenetic analysis of cord blood revealed a karyotype of 47,XY,+21[3]/46,XY[47]. The placenta had a karyotype of 47,XY,+21[8]/46,XY[32], and the umbilical cord had a karyotype of 47,XY,+21[5]/46,XY[35]. Array comparative genomic hybridization analysis on the DNA extracted from cord blood revealed no genomic imbalance. Polymorphic DNA marker analysis excluded uniparental disomy 21. Interphase fluorescence in situ hybridization analysis on urinary cells revealed trisomy 21 signals in 2/102 (1.96%) cells compared with 2/103 (1.94%) cells in normal control. Conclusion The cells of abnormal cell line in prenatally detected mosaic trisomy 21 may decrease in number or disappear in various tissues as the fetus grows, and there exists perinatal cytogenetic discrepancy in mosaic trisomy 21 detected at prenatal diagnosis.

Perinatal cytogenetic discrepancy in a fetus with low-level mosaicism for trisomy 21 and a favorable outcome.

Background Ring chromosome 15 [r (15)] is an uncommon finding with various clinical manifestations. A common phenotype for these patients has not been established and data on the efficacy of recombinant human growth hormone (rhGH) treatment in patients with r (15) syndrome are limited. Methods One short stature patient in our hospital with r (15) syndrome by whole exome sequencing (WES) and karyotype examination was included. All published r (15) syndrome cases as of March 15, 2021, were searched, and their clinical information was recorded and summarized. Results One 11.5-year-old female with prenatal and postnatal growth retardation, ventricular septal defect, intellectual disability, downward corners, short fifth metacarpal bone, scattered milk coffee spots, and a right ovarian cyst was included. Her height was 126.9 cm (-3.45 SDS). Karyotype analysis showed 46, XX, r (15). WES revealed a 4.5 Mb heterozygous deletion in the chromosome 15q26.2-q26.3 region, encompassing genes from ARRDC4 to OR4F15. Gonadotrophin-releasing hormone analogue (triptorelin) and rhGH were administered for 6 months. The height has increased 3.8 cm (+0.2SDS) and the calculated growth rate has improved from 4.7 to 7.6 cm/y. The literature review indicated the main clinical manifestations of r (15) syndrome with prenatal and postnatal growth retardation, characteristic craniofacial features, and multisystem abnormalities, and rhGH treatment is beneficial for r (15) syndrome patients with short stature. Conclusion We delineate the clinical spectrum of r (15) syndrome with the identification of an additional individual and rhGH treatment is beneficial for r (15) syndrome patients with short stature.

The phenotype and rhGH treatment response of ring Chromosome 15 Syndrome: Case report and literature review.

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Paternal UPD14 with sSMC derived from chromosome 14 in Kagami–Ogata syndrome

Objective To present molecular cytogenetic characterization of mosaic supernumerary ring chromosome 8 which has trisomy of a region of chromosome 8p12-q21.13 associated with congenital hypoplasia of the tongue and review of the literature. Case report A 27 year-old woman presented with congenital hypoplasia of the tongue. The chromosome karyotype of peripheral blood lymphocytes was detected by conventional cytogenetic analysis. The genome copy number variations were detected by SNP array. Conventional cytogenetic analysis of the peripheral blood revealed a karyotype of 47,XX,+mar[60]/46,XX[40]. SNP array revealed that there was a duplication of 45.2 Mb at arr[hg19] 8p12q21.13(36,013,636–81,263,140) × 2–3. Conclusion With this study a patient involving mosaic trisomy 8p12-q21.13 along with clinical properties, is described and compared to previously reported cases involving a small supernumerary marker chromosome (sSMC) derived from chromosome 8.

Molecular cytogenetic characterization of mosaicism for a small supernumerary marker chromosome derived from chromosome 8 associated with congenital hypoplasia of the tongue and review of the literature

Trisomy 21 (Tri21), which causes the Down syndrome (DS), is the most common chromosome abnormality [1]. Patients with DS are always accompanied by intellectual disability, congenital heart disease and so on. Therefore, only 20% of Tri21 may progress to term delivery, but it is necessary to prevent the birth of neonatus with Tri21 [1,2]. Noninvasive prenatal testing (NIPT), which is the newest detection method, provides a more precise and fast screening method for the early detection of Tri21, and the detection rate is more than 99% [3]. Nevertheless, the effect of the application of NIPT in the detection of aneuploidy chromosome mosaicism is still uncertain, and it poses a challenge for clinicians to deal with the genetic consultancy of low-level mosaicism after being detected by hypersensitized NIPT. In this article, we present a prenatal diagnosis of low-level mosaicism for trisomy 21 with rare karyotype detected by NIPT. This case involves a 32-year-old woman, presented with a positive result of NIPT for Tri21 and the Z-scores were 4.267. At 20 weeks of gestation, the woman underwent amniocentesis, which followed by fluorescence in situ hybridization (FISH) and chromosome karyotype analysis of amniotic fluid cells. Amniocentesis revealed a karyotype of 47,XX,þ21[20]/47,XX,þder(21) (q21;q21) [30]/46,XX[120] (Fig. 1) and FISH revealed a mosaic level of 5.00%

Prenatal diagnosis of low-level mosaicism for trisomy 21 with rare karyotype detected by noninvasive prenatal testing.

Objective Ring chromosome 15 [r (15)], accompanied by a series of clinical symptoms, is a rare genetic disease. The genotype and phenotypic diversity of patients with r (15) still needed further enrichment. In this study we present a rare case of mosaic ring chromosome 15 with facial anomalies and extremities slenderness. Case report This case involves a 30-year-old woman, unpregnancy within 6 years. Clinical examination of the patient only revealed facial anomalies and extremities slenderness. The result of routine G-band karyotyping was 46,XX,r(15)(p12q26.3)[53]/46,XX,r(15;15)(p11.2q26.3;p11.2q11.2)[28]/45,XX, -15[10]/46,XX,r(15;15)(p11q26.3;p11q26.3)[4]. SNP array was employed to investigate the genome copy number variations (CNVs). The result revealed that there was a micro-duplication of 2.0 Mb at 15q26.3(arr[ph19]15q26.3 (100,400,214- 102,429,112)×3). The duplicated chromosomal section encompassed genes including CHSY1, ALDHIA3, LRRK1, and INS1. We further compared to the cytogenetic characteristics and clinical symptoms of the patient with those already reported by reviewing the literature. Conclusion This report is especially helpful to supplement the phenotypic diversity of patients with r (15).

Zong-Yu Miao

Papers

Molecular cytogenetic characterization of mosaicism for a small supernumerary marker chromosome derived from chromosome 8 associated with congenital hypoplasia of the tongue and review of the literature

Prenatal diagnosis of low-level mosaicism for trisomy 21 with rare karyotype detected by noninvasive prenatal testing.

Clinical, cytogenetic and molecular analyses of a rare case with ring chromosome 15 and review of the literature.