Trisomy 9p Syndrome Research Articles

750 Constitutional reciprocal translocation t(9;22) and pregnancy

To determine the spectrum of cytogenetic abnormalities and outcomes in unbalanced offspring of asymptomatic carriers of a constitutional balanced t(9;22) translocation. A systematic literature review was performed using PubMed and Scopus from inception through March 18, 2020 identifying articles discussing constitutional translocation of chromosomes 9 and 22. We also added a previously unpublished case from our institution of a maternal constitutional balanced t(9;22) translocation. There were 16 patients with balanced t(9;22) translocation, which includes our case. Of these patients, 13 were maternal and 3 were paternal balanced translocations. There were 15 probands with unbalanced translocations from these 16 parental carriers, 1 maternal carrier did not have an unbalanced offspring. Of the probands, 13 were live births, one a missed abortion, and one an elective termination. The spectrum of derivative unbalanced cytogenetics of the livebirth probands were: trisomy 9p syndrome (6 cases), co-existing trisomy 9p syndrome and DiGeorge syndrome (3 cases), co-existing 9q subtelomere deletion syndrome & DiGeorge syndrome (1 case), 9q subtelomere deletion syndrome (1 case), and DiGeorge syndrome (1 case). The phenotypic outcome of unbalanced probands included cardiac defects (5 cases), neurological findings (7 cases), intellectual disabilities (6 cases), urogenital anomalies (3 cases), and respiratory or immune dysfunction (3 cases). If a parent/potential parent is a known constitutional balanced t(9;22) translocation carrier, they should be counseled about the increased risk of having a child with an unbalanced translocation with the aforementioned spectrum of cytogenetic and congenital abnormalities. Additionally, if a pregnancy has been diagnosed with an unbalanced translocation from a carrier parent, families should be counseled on the predicted clinical presentation for the given unbalanced derivative.

Trisomy 12p Syndrome Presenting with Fetal Growth Restriction and Polyhydramnios

A 39-year-old nulliparous woman was referred at 36+6 weeks gestational age, and a prenatal fetal ultrasonography examination found fetal growth restriction (2,190 g <5%), polyhydramnios (amniotic fluid index: 31.76 cm), and absent end-diastolic flow in the umbilical artery. A male baby was born, and fetal dysmorphism including round face, long philtrum, low-set ears, chest retraction, edematous hands and feet, and a simian line on both hands were identified. He was diagnosed with trisomy 12p [der(18)t(12;18)(p11.2;p11.31)] by chromosomal study. The father’s chromosomes appeared normal; however, the mother’s chromosomes had a balanced translocation identified as t(12;18)(p11.2;p11.31). Patent ductus arteriosus, germinal matrix hemorrhage, and hemivertebrae were diagnosed, and respiratory distress, hyperinsulinemic hypoglycemia, and hypothyroidism were also detected. The combination of fetal growth restriction and polyhydramnios may be a significant sign of chromosomal abnormalities, and targeted sonography and a chromosomal analysis should be offered prenatally in such cases.

Treatment of Labial Ulcer Induced by Twisted and Delayed Eruption of Upper Right First Incisor in Patient with 9p Trisomy Syndrome：A Case Report

Treatment of Labial Ulcer Induced by Twisted and Delayed Eruption of Upper Right First Incisor in Patient with 9p Trisomy Syndrome：A Case Report

Trisomy 12p Syndrome Secondary to a Balanced Maternal Translocation [46,XX, t(12;22)(p11.2;p13)

Trisomy 12p is a rare chromosomal anomaly. It causes dysmorphic features, multiple congenital anomalies, neonatal complications, and mental retardation. We present a case of complete and pure trisomy 12p syndrome resulting from malsegregation of a balanced translocation of maternal origin, with a comprehensive literature review.

SNP array analysis of three cases with partial 21q trisomy

To analyze three cases with partial 21q trisomy, and correlate their genotypes with phenotypes. G-banding chromosomal analysis and single nucleotide polymorphism (SNP array) were performed for the three cases and their parents. SNP array has detected partial 21q trisomy in three cases and one mother, with variable size and location of the duplications. Case 1 harbored a 12.35 Mb duplication at 21q22.11q22.3, which spanned the Down syndrome critical region. Case 2 harbored a 35.32 Mb duplication at 9p24.3p13.3 and a 14.42 Mb duplication at 21q11.2q21.3, with the former spanning the partial 9p trisomy syndrome critical region excluding the Down syndrome critical region, and was inherited from his mother. Case 3 harbored a 4.17 Mb tetraploidy at 21q11.2q21.1 in the form of mosaicism, which spared the Down syndrome critical region. His mother carried a 4.17 Mb triploidy at 21q11.2q21.1, which was also a mosaicism. Partial 21q trisomy may occur in various forms and its clinical phenotypes are heterogeneous. Combined use of genetic techniques, particularly SNP array, is crucial for diagnosing partial 21q trisomy and delineating its genotype-phenotype correlation.

Clinical and molecular genetic characterization of two siblings with trisomy 2p24.3-pter and monosomy 5p14.3-pter.

Partial trisomy 2p syndrome is occasionally associated with neural tube defects (NTDs), such as anencephaly, encephalocele, and spina bifida, in addition to common features of intellectual disability, developmental delay, and characteristic facial appearance. The 2p24 region has been reported to be associated with NTDs. Here, we report the cases of 2 siblings with trisomy 2p24.3-pter and monosomy 5p14.3-pter caused by the paternal translocation t(2;5)(p24.3;p14.3). Of the two siblings, the elder sister had spina bifida. We determined the nucleotide sequences of the chromosomal breakpoints and found that the sizes of trisomy 2p and monosomy 5p segments were 18.77 and 17.89 Mb, respectively. NTDs were present in four of seven previously reported patients with trisomy 2p and monosomy 5p as well as in one of the two patients examined in the present study. Although the monosomy 5p of the nine patients were similar in size, the two patients reported here had the smallest size of trisomy 2p. When the clinical features of the nine patients were compared to the present two patients, the elder sister had postaxial polydactyly of the left foot in addition to the characteristic facial appearance and spina bifida, indicating that these features were associated with trisomy 2p24.3-pter. To our knowledge, this is the first study on spina bifida to determine the nucleotide sequences of breakpoints for trisomy 2p24.3-pter and monosomy 5p14.3-pter. Increased gene dosages of dosage-sensitive genes or genes at the trisomy segment (2p24.3) of the presented patients could be associated with NTDs of patients with trisomy 2p.

Nonmosaic partial duplication 12p

We report on a male patient with de-novo pure partial trisomy 12p syndrome besides Robertsonian translocation. The patient had characteristic dysmorphic features such as low-set ear, a high forehead, flat occiput, long philtrum, and nystagmus. He also suffers from intellectual disabilities, seizures, hypotonia, and developmental delay. He has normal anthropometric measurements, and normal height, weight, and skull circumference. A cytogenetic study using the G-banding technique showed 45,XY, add (12)(p12.3), t(13;14)(q10q10). Karyotyping of the parents was performed, which indicated a normal result for the father and 45, XX, t(13;14)(q10;q10) for the mother. The fluorescence in-situ hybridization technique was performed for the patient using whole-chromosome paint 12 and subs telomere 12p. It showed that the add segment on chromosome 12p was derived from chromosome 12 and that 12p subtelomere was inverted and duplicated. Thus, the karyotype is 45, XY, dup (12)(p ter-p12.3), t(13;14)(q10q10). Comparison of the clinical and the cytogenetic findings of our patient with previously reported dup (12p) in the literature was carried out for better characterization and understanding of the phenotypic and cytogenetic relationship.

Report on 3 patients with 12p duplication including GRIN2B

The duplication of the short arm (p) of chromosome 12 is a rare chromosomal abnormality, and most reported cases result from malsegregation of a balanced parental translocation associated with other chromosomal imbalances. Of the reported cases, only 15 involve a pure and complete 12p duplication and only 10 involve a pure and partial duplication overlapping the 12p12.3p13.1 region, including a single instance of an inherited duplication in two related individuals. Here, we report three new patients with a pure 12p duplication, detected by conventional cytogenetic studies and characterized by array-comparative genomic hybridization (array-CGH) and fluorescence in situ hybridization (FISH). The first patient was a child carrying a de novo inverted duplication of the short arm of chromosome 12. His phenotype was similar to that of the “trisomy 12p syndrome”, characterized by developmental delays and craniofacial abnormalities including a high forehead, a short nose with anteverted nostrils and an everted lower lip. The second and third patients were a mother and son with a direct 12p12.3p13.1 duplication, exhibiting a milder phenotype characterized by moderate developmental delays, dysmorphic facial features, behavioral problems and obesity. The present data, including the rarity of the familial cases, should contribute to our knowledge of the genotype/phenotype correlation in trisomy 12p patients.

Absent right superior vena cava with persistent left superior vena cava and normal atrial arrangement

Background: This study aims to investigate the role of echocardiography in the detection of venous anomalies of large thoracic veins in patients with large coronary sinus. Methods: Between January 2010 and March 2012, six patients (3 boys, 3 girls; mean age 4.1; range 3 days - 9 years) were diagnosed with an absent right superior vena cava (RSVC) accompanied by persistent left superior vena cava (PLSVC) in our clinic. The diagnosis of the absent RSVC was established by echocardiography and angiography. Results: Diagnosis of the absent RSVC was confirmed by echocardiography in four patients. The diagnosis was based on cardiac catheterization and angiography in two patients. Additional cardiac anomalies included peripheral pulmonary stenosis, patent ductus arteriosus, tetralogy of Fallot, atrial septal defect, ventricular septal defect and interrupted aortic arch type B. One patient had Trisomy 9p syndrome, while another one was the baby of a diabetic mother. Three patients were followed clinically, while other three patients were operated. Conclusion: Absent RSVC should be thoroughly investigated in cases with a large coronary sinus along with increased coronary sinus flow and PLSVC, as evidenced by echocardiography.

Long-term auxological and endocrinological evaluation of patients with 9p trisomy: a focus on the growth hormone-insulin-like growth factor-I axis

BackgroundTrisomy 9p is an uncommon anomaly characterised by mental retardation, head and facial abnormalities, congenital heart defects, kidney abnormalities, and skeletal malformations. Affected children may also show growth and puberty retardation with delayed bone age. Auxological and endocrinological data are lacking for this syndrome.MethodsWe describe three girls and one boy with 9p trisomy showing substantial growth failure, and we evaluate the main causes of their short stature.ResultsThe target height was normal in all families, ranging from 0.1 and -1.2 standard deviation scores (SDS). The patients had a low birth-weight (from -1.2 to -2.4 SDS), birth length (from -1.1 to -3.2 SDS), and head circumference (from -0.5 to -1.6 SDS). All patients presented with substantial growth (height) retardation at the time of 9p trisomy diagnosis (from -3.0 to -3.8 SDS).The growth hormone stimulation test revealed a classic growth hormone (GH) deficiency (GHD) in patients 1, 3, and 4. In contrast, patient 2 was determined to have a GH neurosecretory dysfunction (GHNSD). The plasma concentrations of IGF-I and IGFBP-3 were low in all patients for their ages and sexes (from -2.0 to -3.4 SDS, and from -1.9 to -2.8 SDS, respectively).The auxological follow-up showed that those patients who underwent rhGH treatment exhibited a very good response to the GH therapy, whereas patients 3 and 4, whose families chose not to use rhGH treatment, did not experience any significant catch-up growth.ConclusionsGH deficiency appears to be a possible feature of patients with 9p trisomy syndrome. These patients, particularly those with growth delays, should be evaluated for GH secretion.

Discordant phenotype in monozygotic twins with mosaic trisomy 12p in lymphocytes

We report on monochorionic diamniotic male twins discordant for the trisomy 12p syndrome. Trisomy 12p mosaicism with a supernumerary der(12)(pter > q12) was detected in approximately 50% of lymphocytes in both children. Fluorescence in situ hybridisation (FISH) revealed a high grade mosaicism of approximately 77% trisomy 12p cells in buccal smear and 85% in hair follicles in the affected twin, while in the normal developing brother an additional 12p chromosome fragment could not be detected in those tissues. Instead, in 3% of buccal smear and hair follicle cells a minute supernumerary marker chromosome comprising central portions of chromosome 12 was observed. Trisomy 12p mosaicism, confined to the lymphocytes of the unaffected twin, may be due to prenatal twin-to-twin transfusion, explaining the conspicuously discordant clinical phenotype. We discuss the possible sequence of events leading to the cytogenetic findings and compare the clinical phenotype presented in the affected twin with other cases of trisomy 12p and tetrasomy 12p (Pallister-Killian syndrome).

Prenatal diagnosis of a fetus with a de novo trisomy 12p by array-comparative genomic hybridization (array-CGH)

Trisomy 12p syndrome is a rare chromosomal abnormality, which presents with facial dysmorphism, moderate to severe psychomotor retardation and generalized hypotonia. Here we present the prenatal sonographic findings investigated of a fetus in prenatal diagnosis with a de novo trisomy of 12p identified by array-comparative genomic hybridization (aCGH).

Array‐CGH study of partial trisomy 9p without mental retardation

Partial trisomy 9p is one of the most common detected autosomal structural anomalies, so the phenotype-genotype correlation of this rearrangement has been well described. Despite variation in size of the 9p duplications, trisomy 9p syndrome is characterized by typical dysmorphic features and a variable but constant psychomotor and mental retardation. Previously reported phenotype genotype correlation studies proposed that the critical region for phenotype is located in 9p22. We report here on a new patient with partial trisomy 9p13.3→9pter in an 8-year-old boy with typical trisomy 9p dysmorphic features but a normal mental development. Cytogenetics investigations showed that our patient karyotype was 47,XY,+ der(22)t(9;22)(p13.q11) inherited by a 3:1 disjunction of a maternal reciprocal translocation t(9;22)(p13.q11). FISH and array CGH analysis were used to better characterize duplicated chromosomal regions and showed a large duplication of chromosome 9p13.3→9pter associated to microduplication in 22q11.1. The size of the duplications in chromosomes 9p and 22q were estimated about 33.9 and 2.67 Mb, respectively. The comparison between this case and those reported in the literature allows us to support that all syndromes show variability and that not all partial trisomies 9p are associated with intellectual disability.

Pure and complete 12p trisomy due to a maternal centric fission of chromosome 12

Pure and complete 12p trisomy are rare. Here, we report on a unique patient with trisomy 12p syndrome due to centric fission of maternal chromosome 12. Conventional cytogenetic and fluorescence in situ hybridization (FISH) techniques revealed the proposita's karyotype to be 47,XX,+fis(12)(p10)mat whereas the maternal one was 47,XX,-12,+fis(12)(p10),+fis(12) (q10). This is the first report on centric fission of chromosome 12 leading to stable telocentrics, each with a fully functional centromere. Our observation shows that the centric fission of chromosome 12 can be a new mechanism for generation of a partial centromere and trisomy 12p syndrome.

Synergistic efficacy of LBH and αB-crystallin through inhibiting transcriptional activities of p53 and p21

LBH is a transcription factor as a candidate gene for CHD associated with partial trisomy 2p syndrome. To identify potential LBH-interacting partners, a yeast two-hybrid screen using LBH as a bait was performed with a human heart cDNA library. One of the clones identified encodes alphaB-crystallin. Co-immunoprecipitation and GST pull-down assays showed that LBH interacts with alphaB-crystallin, which is further confirmed by mammalian two-hybrid assays. Co-localization analysis showed that in COS-7 cells, alphaB-crystallin that is cytoplasmic alone, accumulates partialy in the nucleus when co-transfected with LBH. Transient transfection assays indicated that overexpression of LBH or alphaB-crystallin reduced the transcriptional activities of p53 and p21, respectively, Overexpression of both alphaB-crystallin and LBH together resulted in a stronger repression of the transcriptional activities of p21 and p53. These results showed that the interaction of LBH and alphaB-crystallin may inhibit synergistically the transcriptional regulation of p53 and p21.

Trisomy 12p syndrome secondary to a balanced familial translocation

Trisomy 12p syndrome secondary to a balanced familial translocation

Cytogenetic and molecular characterization of a partial trisomy 2p arising from inverted duplication of 2p with terminal deletion of 2pter

Partial trisomy 2p is typically associated with partial monosomy of another chromosomal segment and results from a balanced translocation in one of the parents. Inverted duplications with terminal deletions have been reported in an increasing number of chromosomes. Several cases initially interpreted as terminal duplications have instead been documented to represent inverted duplications with terminal deletions. Inv dup del(2p) has been reported in patients who manifest the clinical findings of trisomy 2p syndrome. Here we report on a 2-month-old girl with inv dup del(2p) and clinical manifestations that overlap those found commonly in partial 2p trisomy, as previously reported in the literature. Her clinical picture helps delineate the phenotype of 2p duplication disorders.

Trisomy 9p and Prader–Willi syndromes in an infant resulting from a de-novo unbalanced t(9;15) translocation

Trisomy 9p is a well-described dysmorphic syndrome. The physical features include hypertelorism, down-slanting palpebral fissures, deep-set eyes, down-turned corners of the mouth, and mild skeletal anomalies including hypoplastic terminal phalanges. We report an infant born with some of the typical features of trisomy 9p syndrome, as well as additional features that include extreme joint hyperlaxity with subluxation of the knees and elbows, arachnodactyly, and total anomalous pulmonary venous return. The karyotype revealed an unbalanced chromosome complement. Specifically, a derivative chromosome from a de-novo unbalanced translocation of chromosomes 9 and 15 resulted in partial trisomy of 9pter to 9q13 and deletion of the long arm of chromosome 15 proximal to band q13. Fluorescence in-situ hybridization studies and methylation analysis by Southern blotting revealed deletion of the SNRPN locus on the paternally derived chromosome 15, consistent with Prader-Willi syndrome. This infant represents the first reported case of trisomy 9p syndrome with total anomalous pulmonary venous return and hypoplasia of the amygdala and hippocampus, with the additional finding of Prader-Willi syndrome resulting from a derivative chromosome arising from an unbalanced de-novo t(9;15) translocation.

De novo complex intra chromosomal rearrangement after ICSI: characterisation by BACs micro array-CGH

BackgroundIn routine Assisted Reproductive Technology (ART) men with severe oligozoospermia or azoospermia should be informed about the risk of de novo congenital or chromosomal abnormalities in ICSI program. Also the benefits of preimplantation or prenatal genetic diagnosis practice need to be explained to the couple.MethodsFrom a routine ICSI attempt, using ejaculated sperm from male with severe oligozoospermia and having normal karyotype, a 30 years old pregnant woman was referred to prenatal diagnosis in the 17th week for bichorionic biamniotic twin gestation. Amniocentesis was performed because of the detection of an increased foetal nuchal translucency for one of the fetus by the sonographic examination during the 12th week of gestation (WG). Chromosome and DNA studies of the fetus were realized on cultured amniocytesResultsConventional, molecular cytogenetic and microarray CGH experiments allowed us to conclude that the fetus had a de novo pericentromeric inversion associated with a duplication of the 9p22.1-p24 chromosomal region, 46,XY,invdup(9)(p22.1p24) [arrCGH 9p22.1p24 (RP11-130C19 → RP11-87O1)x3]. As containing the critical 9p22 region, our case is in coincidence with the general phenotype features of the partial trisomy 9p syndrome with major growth retardation, microcephaly and microretrognathia.ConclusionThis de novo complex chromosome rearrangement illustrates the possible risk of chromosome or gene defects in ICSI program and the contribution of array-CGH for mapping rapidly de novo chromosomal imbalance.

Familial whole-arm translocations (1;19), (9;13), and (12;21): a review of 101 constitutional exchanges

We report here on 3 familial whole-arm translocations (WATs), namely the 8th instance of t(1;19)(p10;q10) and 2 novel exchanges: t(9;13)(p10;q10) and t(12;21)(p10;q10). The exchanges (1;19) and (12;21) were ascertained through a balanced carrier, whereas the t(9;13) was first diagnosed in a boy with a trisomy 9p syndrome and der(9p13p). Results of FISH analyses with the appropriate ?-satellite probes were as follows. Family 1, t(1;19): the D1Z5 probe gave a strong signal on both the normal chromosome 1 and the der(1q19p) as well as a weak signal on the der(1p19q). Family 2, t(9;13): the centromere-9 alphoid and D13Z1/D21Z1 probes under standard stringency gave no signal on the der(9p13p) in both the proband and a carrier brother, whereas the der(9q13q) was labelled only with the centromere-9 alphoid repeat in the latter; yet, this probe under low stringency revealed a residual amount of alphoid DNA on the der(9p13p) in the carrier. Family 3, t(12;21): the D12Z3 probe gave a signal on the normal chromosome 12 and the der(12p21q), whereas the D13Z1/D21Z1 repeat labelled the der(12q21p), the normal chromosome 21, and both chromosomes 13. Out of 101 WATs compiled here, 73 are distinct exchanges, including 32 instances between chromosomes with common alphoid repeats. Moreover, 7/9 of recurrent WATs involved chromosomes from the same alphoid family. Thus constitutional WATs appear to recur more frequently than other reciprocal exchanges, often involve chromosomes with common alphoid repeats, and can mostly be accounted for the great homology in alphoid DNA that favours mispairing and illegitimate nonhomologous recombination.