SNP array detects chromosome aberrations that we thought do not exist: the first case of an isochromosome Xp (i(X)(p10))

2014 ◽  
Vol 34 (8) ◽  
pp. 806-808 ◽  
Author(s):  
M. I. Srebniak ◽  
M. J. Bos ◽  
F. A. T. de Vries ◽  
R. Heydanus ◽  
M. W. Wessels ◽  
...  
Keyword(s):  
Chromosome Aberrations ◽  
Snp Array ◽  
First Case

scholarly journals A case report and mechanism analysis of a normal phenotype mosaic 47, XXY complicated by paternal iUPD (9) who had a normal PGD result

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Dan Li ◽  
Yun Wang ◽  
Nan Zhao ◽  
Liang Chang ◽  
Ping Liu ◽  
...  
Keyword(s):  
Case Report ◽  
Karyotype Analysis ◽  
Snp Array ◽  
Uniparental Disomy ◽  
Comparative Genomic ◽  
Klinefelter’S Syndrome ◽  
Mechanism Analysis ◽  
Klinefelter's Syndrome ◽  
Preimplantation Genetic Testing ◽  
First Case

Abstract Background Uniparental disomy (UPD) refers to the situation in which two copies of homologous chromosomes or part of a chromosome originate from the one parent and no copy is supplied by the other parent. Case presentation Here, we reported a woman whose karyotype was 46, XX, t (1;17)(q42;q21), has obtained 5 embryos by intracytoplasmic sperm injection (ICSI) after one cycle of in vitro fertility (IVF). After microarray-based comparative genomic hybridization (array-CGH) for preimplantation genetic testing for chromosomal structural rearrangements (PGT-SR), two embryos were balanced, one balanced embryo was implanted and the patient successfully achieved pregnancy. Amniocentesis was performed at the 19th week of gestation for karyotype analysis and single nucleotide polymorphism (SNP)-array test. The result of karyotype analysis was: mos 47, XXY [19]/46, XY [81]; SNP-array results revealed 46, XY, iUPD (9) pat. After full genetic counseling for mosaic Klinefelter’s syndrome and paternal iUPD (9), the couple decided to continue pregnancy, and the patient gave birth to a healthy boy. The newborn is now 3.5 years old, and developed normally. This case will provide counseling evidences of paternal iUPD (9) for doctors. Conclusions This is the first case report of paternal iUPD9 with mosaic Klinefelter’s syndrome, and no abnormality has been observed during the 3.5-year follow-up. Further observation is required to determine whether the imprinted genes on the chromosomes are pathogenic and whether recessive pathogenetic genes are activated.

Genomewide single nucleotide polymorphism microarray mapping for prediction of outcome of neuroblastoma patients

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 9010-9010
Author(s):  
E. Hiyama ◽  
H. Yamaoka ◽  
A. Kamimatsuse ◽  
M. Onitake ◽  
T. Sueda ◽  
...  
Keyword(s):  
Chromosome Aberrations ◽  
Expression Profiles ◽  
Snp Array ◽  
Genetic Alterations ◽  
Mycn Amplification ◽  
Genome Wide ◽  
Whole Genome Microarray ◽  
History Of ◽  
Gain Loss ◽  
Almost All

9010 Background: Neuroblastoma is a biologically and genetically heterogeneous tumor and demonstrates favorable or unfavorable outcomes. However, the number of subgroups in neuroblastoma and natural history of each subgroup remain unclear. In Japan, nation-wide neuroblasotma mass-screening (MS) project had been performed on 6-month-old babies for 20 years that might have detected almost all neuroblastomas including regressing/ maturing tumors developed in this period. We surveyed more than 3,600 neuroblasotma cases including approximately 2,000 MS detecting cases. In this study, we examined genetic alterations in the representative cases using genome-wide SNP array and compared with the clinical courses. Methods: Genomic DNA was extracted from 198 neuroblastoma samples. SNP array (Affimetrix GeneChip Human mapping Array100K) was used to determine genome-wide aberrations. Chromosome aberrations were confirmed by BAC array and FISH examination. Expression profiles of these tumors were also examined using whole genome microarray (Codelink and Affimetrix Array U133 plus2). Results: SNP arrays could frequently identify chromosomal aberrations and allelic imbalances including 1p and 11q loss and MYCN amplification in unfavorable tumors. Then, we broadly classified the chromosome aberrations in neuroblastoma into four types: whole gain/loss type, partial gain/loss type, MYCN amplified type, and silent type with no large alterations. Almost all tumors with whole gain/loss type showed favorable prognosis, while MYCN amplified type and partial gain/loss type showed unfavorable outcome. In 32 tumors with silent type, 18 unfavorable tumors had small deletions and/or gains in 1p, 2p, 3p, 11q, and/or 17q but the remaining 16 favorable cases did not. The expression analysis of the unfavorable tumors showed high expression of several genes (DDX1, NAG, NME1, MAC30) in these loci. Conclusions: Genome-wide genetic analysis classified neuroblastoma into four types, which are useful to predict the outcome of patients. In the silent type, unfavorable tumors revealed several genes to predict the outcome of the patients. These data provided important candidates of indicators for risk assessment and of therapeutic targets for unfavorable neuroblastoma. No significant financial relationships to disclose.

A case of paternal uniparental isodisomy for chromosome 7 associated with overgrowth

2018 ◽  
Vol 55 (8) ◽  
pp. 567-570 ◽  
Author(s):  
Akie Nakamura ◽  
Koji Muroya ◽  
Hiroko Ogata-Kawata ◽  
Kazuhiko Nakabayashi ◽  
Keiko Matsubara ◽  
...  
Keyword(s):  
Snp Array ◽  
Uniparental Disomy ◽  
Chromosome 7 ◽  
Comparative Genomic Hybridisation ◽  
Comparative Genomic ◽  
Tall Stature ◽  
Methylation Analysis ◽  
Inherited Disorders ◽  
First Case ◽  
Uniparental Isodisomy

BackgroundPaternal uniparental disomy for chromosome 7 (upd(7)pat) is extremely rare, and only four cases have been previously reported. As these cases were accompanied by autosomal-recessive disorders which are likely to be involved in growth restriction, the relevance of upd(7)pat to the overgrowth phenotype remains unclear. Here we describe one case of upd(7)pat with no additional genetic diseases, which may answer the question.MethodsA 5-year-old Japanese boy presented with a tall stature of unknown causes. To detect the genetic cause of the tall stature, we performed Sanger sequencing, targeted resequencing, comparative genomic hybridisation and single-nucleotide polymorphism (SNP) array analyses, methylation analysis and microsatellite analysis.ResultsWe could not detect pathogenic variants in causative genes for overgrowth syndrome or apparent copy number alterations. DNA methylation analysis revealed hypomethylation at the GRB10, PEG1 and PEG10 differentially methylated regions. SNP array and microsatellite analyses suggested paternal uniparental isodisomy for chromosome 7. Furthermore, we could not identify homozygous mutations of known causative genes for inherited disorders on chromosome 7.ConclusionWe report the first case of upd(7)pat with an overgrowth phenotype.

scholarly journals Paternal Uniparental Disomy of the Entire Chromosome 20 in a Child with Beckwith-Wiedemann Syndrome

Genes ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 172
Author(s):  
Sanaa Choufani ◽  
Jung Min Ko ◽  
Youliang Lou ◽  
Cheryl Shuman ◽  
Leona Fishman ◽  
...  
Keyword(s):  
Snp Array ◽  
Uniparental Disomy ◽  
Chromosome 1 ◽  
Single Individual ◽  
Imprinting Disorders ◽  
Chromosome 20 ◽  
First Case ◽  
Entire Chromosome ◽  
Paternal Uniparental Disomy ◽  
Chromosome 11P15.5

Epigenetic alterations at imprinted genes on different chromosomes have been linked to several imprinting disorders (IDs) such as Beckwith-Wiedemann syndrome (BWS) and pseudohypoparathyroidism type 1b (PHP1b). Here, we present a male patient with these two distinct IDs caused by two independent mechanisms-loss of methylation (LOM) at chromosome 11p15.5 associated with multi-locus imprinting disturbances (MLID and paternal uniparental disomy of chromosome 20 (patUPD20). A clinical diagnosis of BWS was made based on the clinical features of macrosomia, macroglossia, and umbilical hernia. The diagnosis of PHP1b was supported by the presence of reduced growth velocity and mild learning disability as well as hypocalcemia and hyperphosphatemia at 14 years of age. Molecular analyses, including genome-wide DNA methylation (Illumina 450k array), bisulfite pyrosequencing, single nucleotide polymorphism (SNP) array and microsatellite analysis, demonstrated loss of methylation (LOM) at IC2 on chromosome 11p15.5, and paternal isodisomy of the entire chromosome 20. In addition, imprinting disturbances were noted at the differentially methylated regions (DMRs) associated with DIRAS3 on chromosome 1 and PLAGL1 on chromosome 6. This is the first case report of PHP1b due to patUPD20 diagnosed in a BWS patient with LOM at IC2 demonstrating etiologic heterogeneity for multiple imprinting disorders in a single individual.

scholarly journals The First Case of Congenital Myasthenic Syndrome Caused by a Large Homozygous Deletion in the C-Terminal Region of COLQ (Collagen Like Tail Subunit of Asymmetric Acetylcholinesterase) Protein

Genes ◽  
2020 ◽  
Vol 11 (12) ◽  
pp. 1519
Author(s):  
Nicola Laforgia ◽  
Lucrezia De Cosmo ◽  
Orazio Palumbo ◽  
Carlotta Ranieri ◽  
Michela Sesta ◽  
...  
Keyword(s):  
Chromosome Region ◽  
Snp Array ◽  
Homozygous Deletion ◽  
Congenital Myasthenic Syndrome ◽  
Therapeutic Implications ◽  
Molecular Approaches ◽  
First Case ◽  
Pakistani Origin ◽  
Myasthenic Syndrome ◽  
Exon 11

Congenital myasthenic syndromes (CMSs) are caused by mutations in genes that encode proteins involved in the organization, maintenance, function, or modification of the neuromuscular junction. Among these, the collagenic tail of endplate acetylcholinesterase protein (COLQ; MIM 603033) has a crucial role in anchoring the enzyme into the synaptic basal lamina. Here, we report on the first case of a patient with a homozygous deletion affecting the last exons of the COLQ gene in a CMS patient born to consanguineous parents of Pakistani origin. Electromyography (EMG), electroencephalography (EEG), clinical exome sequencing (CES), and single nucleotide polymorphism (SNP) array analyses were performed. The subject was born at term after an uneventful pregnancy and developed significant hypotonia and dystonia, clinical pseudoseizures, and recurring respiratory insufficiency with a need for mechanical ventilation. CES analysis of the patient revealed a homozygous deletion of the COLQ gene located on the 3p25.1 chromosome region. The SNP-array confirmed the presence of deletion that extended from exon 11 to the last exon 17 with a size of 19.5 Kb. Our results add new insights about the underlying pathogenetic mechanisms expanding the spectrum of causative COLQ mutations. It is relevant, considering the therapeutic implications, to apply suitable molecular approaches so that no type of mutation is missed: “each lost mutation means a baby treated improperly”.

scholarly journals Centromere Repositioning in Cattle (Bos taurus) Chromosome 17

2017 ◽  
Vol 151 (4) ◽  
pp. 191-197 ◽  
Author(s):  
Lisa De Lorenzi ◽  
Alessandra Iannuzzi ◽  
Elena Rossi ◽  
Stefania Bonacina ◽  
Pietro Parma
Keyword(s):  
Array Cgh ◽  
Bos Taurus ◽  
Snp Array ◽  
Pericentromeric Region ◽  
Chromosome 17 ◽  
Medium Size ◽  
Fish Analysis ◽  
Primary Constriction ◽  
First Case ◽  
Eukaryotic Organisms

Eukaryotic organisms have developed a structure, called centromere, able to preserve the integrity of the genome during cell division. A young bull from the Marchigiana breed, with a normal external phenotype, underwent routine cytogenetic analysis to enter the reproduction center. All metaphases analyzed showed an unusual biarmed chromosome of medium size despite a diploid set of chromosomes (2n = 60,XY). FISH analysis excluded a pericentric inversion or a reciprocal translocation, but highlighted a repositioning of the centromere in BTA17. The satellite DNA was still in an acrocentric position. The telomeres were normally present. The primary constriction on the abnormal chromosome was C-band negative. Finally, the absence of a large genomic deletion in the BTA17 pericentromeric region was demonstrated by both array-CGH analysis and SNP array. To our knowledge, this is the first case of centromere repositioning reported in cattle.

First Report of Low-Rate Mosaicism for 20q11.21q12 Deletion and Delineation of the Associated Disorder

2018 ◽  
Vol 156 (2) ◽  
pp. 87-94
Author(s):  
Sara Loddo ◽  
Viola Alesi ◽  
Silvia Genovese ◽  
Valeria Orlando ◽  
Chiara Calacci ◽  
...  
Keyword(s):  
Growth Retardation ◽  
Snp Array ◽  
Small Region ◽  
Growth Delay ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Psychomotor Delay ◽  
Feeding Difficulties ◽  
First Case ◽  
Snp Array Analysis

Interstitial deletions of the long arm of chromosome 20 are very rare, with only 12 reported patients harboring the 20q11.2 microdeletion and presenting a disorder characterized by psychomotor and growth delay, dysmorphisms, and brachy-/clinodactyly. We describe the first case of mosaic 20q11.2 deletion in a 5-year-old girl affected by mild psychomotor delay, feeding difficulties, growth retardation, craniofacial dysmorphisms, and finger anomalies. SNP array analysis disclosed 20% of cells with a 20q11.21q12 deletion, encompassing the 20q11.2 minimal critical region and the 3 OMIM disease-causing genes GDF5, EPB41L1, and SAMHD1. We propose a pathogenic role of other genes mapping outside the small region of overlap, in particular GHRH (growth hormone releasing hormone), whose haploinsufficiency could be responsible for the prenatal onset of growth retardation which is shared by half of these patients. Our patient highlights the utility of chromosomal microarray analysis to identify low-level mosaicism.

scholarly journals A Novel Genetic Variant in the WFS1 Gene in a Patient with Partial Uniparental Mero-Isodisomy of Chromosome 4

2021 ◽  
Vol 22 (15) ◽  
pp. 8082
Author(s):  
Maurizio Delvecchio ◽  
Federica Ortolani ◽  
Orazio Palumbo ◽  
Concetta Aloi ◽  
Alessandro Salina ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Genetic Variant ◽  
Novel Mutation ◽  
Blood Glucose Control ◽  
Snp Array ◽  
Uniparental Disomy ◽  
Wolfram Syndrome ◽  
Chromosome 4 ◽  
Rapid Reduction ◽  
First Case

Wolfram syndrome is a rare autosomal recessive disorder characterized by optic atrophy and diabetes mellitus. Wolfram syndrome type 1 (WFS1) is caused by bi-allelic pathogenic variations in the wolframin gene. We described the first case of WFS1 due to a maternal inherited mutation with uniparental mero-isodisomy of chromosome 4. Diabetes mellitus was diagnosed at 11 years of age, with negative anti-beta cells antibodies. Blood glucose control was optimal with low insulin requirement. No pathogenic variations in the most frequent gene causative of maturity-onset diabetes of the young subtypes were detected. At 17.8 years old, a rapid reduction in visual acuity occurred. Genetic testing revealed the novel homozygous variant c.1369A > G; p. Arg457Gly in the exon 8 of wolframin gene. It was detected in a heterozygous state only in the mother while the father showed a wild type sequence. In silico disease causing predictions performed by Polyphen2 classified it as “likely damaging”, while Mutation Tester and Sift suggested it was “polymorphism” and “tolerated”, respectively. High resolution SNP-array analysis was suggestive of segmental uniparental disomy on chromosome 4. In conclusion, to the best of our knowledge, we describe the first patient with partial uniparental mero-isodisomy of chromosome 4 carrying a novel mutation in the wolframin gene. The clinical phenotype observed in the patient and the analysis performed suggest that the genetic variant detected is pathogenetic.

scholarly journals The 46, XX Ovotesticular Disorder of Sex Development With Xq27.1q27.2 Duplication Involving the SOX3 Gene: A Rare Case Report and Literature Review

2021 ◽  
Vol 9 ◽  
Author(s):  
Jianlong Zhuang ◽  
Chunnuan Chen ◽  
Jia Li ◽  
Yuying Jiang ◽  
Junyu Wang ◽  
...  
Keyword(s):  
Gene Duplication ◽  
Rare Case ◽  
Snp Array ◽  
Case Presentation ◽  
Disorder Of Sex Development ◽  
Sex Development ◽  
First Case ◽  
Rare Case Report ◽  
Snp Array Analysis ◽  
Chinese Individual

Background: Very few reports are available on human XX ovotesticular disorder of sex development involving SOX3 gene duplication. Here we aim to present a rare case of SOX3 gene duplication in a person from the Chinese population who exhibits XX ovotesticular disorder of sex development.Case Presentation: A 7-year-old Chinese individual from Fujian province in Southeast China was recruited. The patient presented 46, XX karyotype, absence of sex-determining region Y, and was diagnosed with XX ovotesticular disorder of sex development. Furthermore, SNP array analysis demonstrated that the patient had a 2.2-Mb duplication in the Xq27.1q27.2 region (arr[hg19]Xq27.1q27.2:139,499,778-141,777,782) involving the SOX3 gene. Additionally, no SOX3 duplication was observed in the parents or the sibling, who displayed none of the clinical features.Conclusion: We identified the first case of SOX3 duplication in a Chinese individual who exhibits ovotesticular disorder of sex development. Our study strengthens the link between the SOX3 duplication and XX ovotesticular disorder of sex development and indicates that SOX3 is the evolutionary antecedent of sex-determining region Y.

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