Trisomy 9p Research Articles

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.

Limited survivability of unbalanced progeny of carriers of a unique t(4;19)(p15.32;p13.3): a study in multiple generations

BackgroundCarriership of a reciprocal chromosomal translocation (RCT) involving the short arm of chromosome 4 (4p) may result in birth of a child with Wolf-Hirschhorn syndrome (WHS) due to monosomy 4p, a priori modified by the impact of the partner chromosome imbalance. Familial transmission studies of RCT enable obtaining empirical risk figures that are essential for genetic counseling. In this study, pedigree data from carriers of a unique t(4;19)(p15.32;p13.3), ascertained by two children with WHS phenotype, were collected through five generations and empirical risk for different pregnancy outcomes was assessed. In addition, the phenotype-karyotype correlation was studied in two unbalanced children against the phenotypes of children (literature data) with pure monosomy 4p15.32 → pter and pure trisomy 19p13.3 → pter, accordingly. The phenotype analysis was conducted using the catalogue of traits according to the Munich Dysmorphology Database. Pedigree segregation analysis was conducted by the direct method according to Stengel- Rutkowski et al.ResultsA double segment imbalance, trisomy 19p13.3 → pter with monosomy 4p15.32 → pter, was diagnosed in WHS progeny at birth. No essential modification of WHS phenotype by the additional trisomy 19p was observed, except for a limited survivability (death in infancy). Pedigree segregation analysis covered 39 relatives showed the probability rate for liveborn with unbalanced karyotype of 3.7 ± 3.6% (1/27), for stillbirth/neonatal death at 7.4 ± 5.0% (2/27), for miscarriage at 22.2 ± 8.0% (6/27), for the chance of having a baby without unbalanced karyotype was estimated at 66.7 ± 9.1% (18/27). In addition, the value of 7.4% for genetic counseling for any carrier of RCT at risk for single segment 19p13.3 → pter imbalance at birth was evaluated as such value have not been estimated so far.ConclusionCarriership of a t(4;19)(p15.32;p13.3) is at low risk for an unbalanced child at birth and for stillbirth/neonatal death but high for miscarriages. The chance of having a baby without unbalanced karyotype was estimated to be high. Monosomy 4p15.32 → pter together with trisomy 19p13.3 → pter as a double segment imbalance in children with WHS may be connected with a limited survivability in infancy.

Prenatal diagnosis of a foetus with partial monosomy 4p and partial trisomy 13q

Alopecia areata (AA) is an autoimmune, nonscarring hair loss disorder with slightly greater prevalence in children than adults. Various treatment modalities exist; however, their evidence in pediatric AA patients is lacking.To evaluate the evidence of current treatment modalities for pediatric AA.We conducted a systematic review on the PubMed database in October 2019 for all published articles involving patients <18 years old. Articles discussing AA treatment in pediatric patients were included, as were articles discussing both pediatric and adult patients, if data on individual pediatric patients were available.Inclusion criteria were met by 122 total reports discussing 1032 patients. Reports consisted of 2 randomized controlled trials, 4 prospective comparative cohorts, 83 case series, 2 case-control studies, and 31 case reports. Included articles assessed the use of aloe, apremilast, anthralin, anti-interferon gamma antibodies, botulinum toxin, corticosteroids, contact immunotherapies, cryotherapy, hydroxychloroquine, hypnotherapy, imiquimod, Janus kinase inhibitors, laser and light therapy, methotrexate, minoxidil, phototherapy, psychotherapy, prostaglandin analogs, sulfasalazine, topical calcineurin inhibitors, topical nitrogen mustard, and ustekinumab.English-only articles with full texts were used. Manuscripts with adult and pediatric data were only incorporated if individual-level data for pediatric patients were provided. No meta-analysis was performed.Topical corticosteroids are the preferred first-line treatment for pediatric AA, as they hold the highest level of evidence, followed by contact immunotherapy. More clinical trials and comparative studies are needed to further guide management of pediatric AA and to promote the potential use of pre-existing, low-cost, and novel therapies, including Janus kinase inhibitors.

Familial Translocation t(5;15)(p14.2;q26.2) Causing a Mirror Combination of Several Known Genetic Conditions

AbstractTwo siblings with an unbalanced cytogenetic composition are described: a brother with partial trisomy 5p and distal 15q microdeletion, and a sister with partial monosomy 5p and distal 15q microduplication, resulting from a familial balanced translocation 46,XY; t(5;15)(p14.2;q26.2). To our best knowledge, there are no previous clinical and cytogenetic reports in the literature describing a family with concomitant presence of such a unique mirror combination. Clinical features of pure imbalances and the effects of their combination are discussed.

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.

Prenatal diagnosis of a de novo trisomy 9p fetus with a positive non-invasive prenatal testing result

Prenatal diagnosis of a de novo trisomy 9p fetus with a positive non-invasive prenatal testing result

Constitutional 560.49 kb chromosome 2p24.3 duplication including the MYCN gene identified by SNP chromosome microarray analysis in a child with multiple congenital anomalies and bilateral Wilms tumor

Fewer than 100 patients with partial chromosome 2p trisomy have been reported. Clinical features are variable and depend on the size of the duplicated segment, but generally include psychomotor delay, facial anomalies, congenital heart defect, and other abnormalities. We report a 560.49 kb duplication of chromosome 2p in a 13 month-old male with hydrocephaly, ventricular septal defect, partial agenesis of the corpus callosum, and bilateral Wilms tumor. After discovery of bilateral renal masses at four months of age, the child underwent neoadjuvant chemotherapy followed by right radical nephrectomy that revealed triphasic Wilms' tumor. A needle core biopsy on one of two lesions on the left kidney also revealed Wilms tumor. A partial left nephrectomy revealed focally positive margins that necessitated left flank radiotherapy. The tumor karyotype was 46,XY,t(7;8)(q36;p11)[8]/46,XY [12] while his constitutional karyotype was 46,XY, suggesting that the t(7;8)(q36;p11) was associated with the malignancy. Single nucleotide polymorphism (SNP) chromosome microarray analysis of peripheral blood identified a maternally-inherited 560.49 kb chromosome 2p24.3 duplication that involved four OMIM genes: NBAS, DDX1, MYCNOS, and MYCN. SNP array analysis of the tumor revealed the same 2p24.3 duplication. At present, the now 5-year-old boy continues to do well without clinical or radiographic evidence of recurrent disease. This case is instructive because the child's health insurer initially denied authorization for chromosome microarray analysis (CMA), and it took more than one year before such authorization was finally granted. That initial decision to deny coverage could have had untoward health implications for this child, as the identification of constitutional MYCN duplication necessitated surveillance imaging for a number of pediatric malignancies associated with MYCN overexpression/dysregulation.

Prenatal diagnosis of partial monosomy 5p (5p15.1→pter) and partial trisomy 7p (7p15.2→pter) associated with cystic hygroma, abnormal skull development, and ventriculomegaly

ObjectivePrenatal diagnosis of concomitant chromosome 5p deletion syndrome and chromosome 7p duplication syndrome in a fetus with abnormal prenatal ultrasound is presented. Case ReportA 34-year-old woman was referred for amniocentesis at 22 weeks of gestation because of an irregular-shaped skull, bilateral ventriculomegaly, and nuchal cystic hygroma. Amniocentesis revealed a derivative chromosome 5 with a distal 5p deletion and an addendum of an extra unknown chromosomal segment at the breakpoint of 5p. Cytogenetic analysis of parental bloods revealed a karyotype of 46, XX, t(5;7)(p15.1;p15.2) in the mother and a karyotype of 46,XY in the father. The karyotype of the fetus was 46, XX, der(5) t(5;7)(p15.1;p15.2)mat consistent with partial monosomy 5p (5p15.1→pter) and partial trisomy 7p (7p15.2→pter). A malformed fetus was subsequently delivered with an irregular-shaped skull, a large anterior fontanelle, brachycephaly, hypertelorism, a high and prominent forehead, a large nuchal cystic hygroma, large low-set ears, a short and flattened nose, and micrognathia. Array comparative genomic hybridization analysis of the placenta revealed the result of arr 5p15.33p15.1 (22,179-18,133,327)×1.0, 7p22.3p15.2 (54,215-25,551,540)×3.0, indicating an 18.11-Mb deletion of 5p (5p15.33-p15.1) and a 22.5-Mb duplication of 7p (7p22.3-p15.2). Cord blood sampling revealed a karyotype of 46, XX, der(5)t(5;7) (p15.1;p15.2)mat. ConclusionFetuses with 5p deletion syndrome and 7p duplication syndrome may present ventriculomegaly, abnormal skull development, and cystic hygroma on prenatal ultrasound.

Distal Trisomy 10p and 4q Monosomy: Associated with Marfanoid Features, Syndromic Aortic Root Dilatation and Intellectual Disability

Distal Trisomy 10p and 4q Monosomy: Associated with Marfanoid Features, Syndromic Aortic Root Dilatation and Intellectual Disability

Trisomía parcial 9p derivada de una translocación recíproca 9;15, materna. Reporte de casos

Objectives: to highlight the importance of performing karyotype in children with congenital malformations in order to have a confirmatory diagnosis, in parents to exclude the possibility of being carriers of chromosomal abnormalities and perform the genetic counseling. Clinical cases description: Female patient with 3 years and 2 months old to whom karyotype was performed by global neurodevelopmental delay and microcephaly, and her mother with 34 years old without any clinical manifestations, to both patients, lymphocyte culture and chromosomal analysis with a High Resolution Banding techniques GTG and C were performed. The mother’s karyotype was 46,XX,t(9;15)(q10;q10)(p10;p10),add14p. The father’s karyotype was normal, 46,XY, and the girl’s karyotype resulted in a pure Trisomy 9p: 47,XX,+del(9)(q11). Discussion: This chromosomal rearrangement in mother included a nonhomologous reciprocal translocation between the long arms of pair chromosomes 9 and 15 and between the short arms of the same chromosomes, additional to it, an unknown origin material was also observed in short arm from one chromosome of the 14 pair. In meiosis of this type of rearrangement, the father’s normal homologous chromosomes are paired with the mother’s translocated chromosomes and as a result of 3:1 segregation a gamete with one chromosome else was originated that after fertilization resulted in an unbalanced translocation confirming the pure trisomy in the patient.

CASE REPORT-chromosome 9p trisomy with insulin dependent diabetes

CASE REPORT-chromosome 9p trisomy with insulin dependent diabetes

MG-121 Complexity of phenotypes of females with unbalanced x-autosomal translocations exemplified by a case with 46, x,der (x)t (x;16)(p11.2;p13.2) karyotype

Background Females with unbalanced X-autosomal translocations frequently exhibit skewed X-chromosome inactivation, as cells with the least functional imbalance have selective advantage. However, predicting the inactivation status of the translocated autosomal segment and its impact on phenotype is challenging. Active vs inactive state can depend on translocation breakpoint and sequence features of the translocated segment. Objective Report a case with 46,X,der (X)t (X;16)(p11.2;p13.2) karyotype and discuss karyotype/phenotype correlations. Results We report a 18 month old girl with intrauterine growth restriction, failure to thrive, cardiac anomalies and dysmorphic features. Oligonucleotide microarray has revealed a terminal ~9 Mb gain of chromosome 16p and terminal loss of most of Xp. A de novo unbalanced translocation t (X;16)(p11.2;p13.2) was confirmed by karyotype analysis and family studies. Androgen receptor assay further showed complete skewing of X-inactivation, suggesting that derivative X-chromosome was inactive. Phenotype of our patient was not fully consistent with either Xp deletion or 16p13.3 duplication, leaving a question about inactivation status of the translocated 16p material. A case with 46, X,der (X) t (X;16)(q28;p12) karyotype and phenotype consistent with 16p13.3 duplication syndrome was previously reported. Replication studies have shown skewed inactivation of the der (X), not spreading into 16p translocated segment. 1 Conclusions Our patient phenotype suggests that while Androgen Receptor assay provides valuable information in regard of X-inactivation skewing, it has limitations for karyotype/phenotype correlations for patients with unbalanced X-autosomal translocation. Additional analysis of inactivation status of the genes of the translocated segment is underway to understand the phenotype of our patient. Reference Preis W, Barbi G, Liptay S, Kennerknecht I, Schwemmle S, Pohlandt F. X/autosome translocation in three generations ascertained through an infant with trisomy 16p due to failure of spreading of X-inactivation. Am J Med Genet . 1996; 61 (2):117–21

Tri-allelic TPOX genotype observed in engraftment monitoring baseline

Aim TPOX is a short tandem repeat (STR) DNA locus having a four nucleotide repeat pattern (AATG). It is seen to have a greater frequency of tri-allelic genotypes than other STRs, although such genotypes are relatively rare overall. Here we describe a tri-allelic genotype found in the TPOX DNA locus of an engraftment monitoring baseline sample. Methods DNA was extracted from a patient’s pre-transplant peripheral blood lymphocytes using the Qiagen Mini Blood Kit. This DNA was amplified on an Applied Biosystems 9700 thermocycler using Promega’s PowerPlex16 System human identity kit. The amplicon was run on an Applied Biosystems 3130xl Genetic Analyzer, and the data evaluated with GeneMapper ID-X software. Results The DNA profile appeared normal, except in the TPOX locus (2p23-2pter). TPOX presented an 8-9-10 genotype with the three alleles having similar intensity. This is one of two types of tri-allelic pattern that might be discerned, the other having two alleles with different intensity than the third. The observed pattern suggests a chromosomal rearrangement. Karyotype analysis showed no occurrence of 2p trisomy. Conclusion We report a TPOX tri-allelic subject where the tri-allelic pattern is not the result of a visible 2p trisomy. This is concordant with other findings of allele 10 being the predominant extra TPOX allele and suggesting that it is transmitted on the X chromosome.

Prenatal diagnosis of a case with combined Wolf-Hirschhorn syndrome and Jacobsen syndrome

To detect chromosomal imbalance in a fetus with complex congenital heart disease, and to correlate the genotype with the phenotype. Routine G-banding was carried out to analyze the karyotypes of the fetus and its parents, and single nucleotide polymorphisms array (SNP-array) was used for delineating fine genomic aberrations. The detected aberrations were confirmed with multiplex ligation-dependent probe amplification (MLPA). The fetus and its parents all showed a normal karyotype, while array-SNP has detected a 13.87 Mb duplication at 4p16.3-p15.33 and a 15.65 Mb deletion at 11q23.3-q25 in the fetus. The results were confirmed by the MLPA assay. The partial trisomy 4p (Wolf-Hirschhorn syndrome) and partial monosomy 11q (Jacobsen syndrome) probably underlie the complex heart defects detected in the fetus. Analysis of the karyotypes of its parents offered no help for the determination of the aberrant type and recurrent risk. Compared with routine karyotype analysis, aberrant regions can be identified with array-SNP with greater resolution and accuracy. This has provided useful information for prenatal diagnosis and genetic counseling.

Clinical features of a case with trisomy 10q and monosomy 3p resulting from a maternal balanced translocation

Here we describe clinical and cytogenetic data on 2-year-old female child with partial trisomy for the distal part of the long arm of chromosome 10 (10q22–>qter) and a concomitant monosomy 3(p25–>pter) as a result of a maternal balanced reciprocal translocation. Her karyotype was ascertained as 46,XX,der(3)t(3;10)(p25;q22). The father had normal karyotype. The mother had an apparently balanced translocation involving chromosome 3 and 10 [46,XX,t(3;10)(p25;q22)]. This is the second reported case of partial trisomy 10q and partial trisomy 3p. Clinical features of this case and a few published cases will be reviewed briefly.

Large Cryptic Derivative Chromosome 8 Detected by SNP Chromosomal Microarray

Large Cryptic Derivative Chromosome 8 Detected by SNP Chromosomal Microarray

Streamlining NGS Workflows Using Cancer Samples by the Application of Tthe DNA Integrity Number (DIN) from the Genomic DNA Screentape Assay

Streamlining NGS Workflows Using Cancer Samples by the Application of Tthe DNA Integrity Number (DIN) from the Genomic DNA Screentape Assay

Partial trisomy 4q and partial monosomy 9p in a girl with choanal atresia and various dysmorphic findings

We report a new-born girl with partial trisomy of 4q28-qter and partial monosomy of 9p24-9ter. Our patient has choanal atresia, hypertelorism, wide nasal bridge, high arched palate, discrete nipples, heart defects, myoclonic seizures and various dysmorphic findings. Standard chromosomal analysis with G-banding with Trypsin-Giemsa revealed 46,XX,der(9)t(4;9)(q28;p24) resulting from the mother's t(4,9) (q28;p24) karyotype. Deletions of the terminal part of 9p and partial trisomy of chromosome 4q are rare chromosomal alterations. To our knowledge, this is the first report of choanal atresia in a patient with a partial trisomy of 4q28-qter and partial monosomy 9p24-9ter combination, which were detected by integrated cytogenetic and genomic analysis.

4p16.1-p15.31 duplication and 4p terminal deletion in a 3-years old Chinese girl: Array-CGH, genotype-phenotype and neurological characterization

Microscopically chromosome rearrangements of the short arm of chromosome 4 include the two known clinical entities: partial trisomy 4p and deletions of the Wolf-Hirschhorn critical regions 1 and 2 (WHSCR-1 and WHSCR-2, respectively), which cause cranio-facial anomalies, congenital malformations and developmental delay/intellectual disability. We report on clinical findings detected in a Chinese patient with a de novo 4p16.1-p15.32 duplication in association with a subtle 4p terminal deletion of 6Mb in size. This unusual chromosome imbalance resulted in WHS classical phenotype, while clinical manifestations of 4p trisomy were practically absent. This observation suggests the hypothesis that haploinsufficiency of sensitive dosage genes with regulatory function placed in WHS critical region, is more pathogenic than concomitant 4p duplicated segment. Additionally clinical findings in our patient confirm a variable penetrance of major malformations and neurological features in Chinese children despite of WHS critical region's deletion.

Trisomía parcial 4p por cromosoma 4 recombinante originado por inversión pericéntrica de origen paterno

La trisomía parcial 4p, suele originarse de translocaciones entre el cromosoma 4 y otros cromosomas no homólogos o por inversión pericéntrica del cromosoma 4, originando gametos anómalos entre el cromosoma normal y el invertido, obteniéndose un cromosoma recombinante que puede portar duplicidad de segmentos del brazo pequeño (4p) o del brazo largo (4q) siendo este último inviable. Las características fenotípicas de esta condición cursan con retardo mental severo, retraso en el desarrollo psicomotor, anomalías craneofaciales, estrabismo, defectos osteomusculares, defectos cardiacos, criptorquidia y micropene. Describimos el caso de un niño de 1 año 6 meses con retardo en el desarrollo psicomotor y rasgos dismórficos, presentando una duplicación 4p recombinante de origen paterno.Es el primer caso de duplicación 4p hallado en nuestra institución y debido al carácter hereditario, es preciso realizar la consejería a los progenitores y seguimiento del propósitos para su manejo terapéutico y psicológico.