A case of 46,XX dysgenesis and marked tall stature; the need for caution in interpreting array comparative genomic hybridization (CGH)

2016 ◽  
Vol 29 (12) ◽  
Author(s):  
Vidya Kanamkote Narayanan ◽  
Mira Kharbanda ◽  
Malcolm Donaldson
Keyword(s):  
Gonadal Dysgenesis ◽  
Array Cgh ◽  
Ethinyl Estradiol ◽  
Standard Deviation Score ◽  
Breast Development ◽  
Comparative Genomic ◽  
Cylindrical Shape ◽  
Tall Stature ◽  
Height Measurement ◽  
Critical Height

Abstract Background: Gonadal dysgenesis with an apparently normal 46,XX karyotype is a rare cause of hypergonadotrophic hypogonadism. Tall stature is not a widely recognized association. Case report: A 15-year-old girl presented with primary amenorrhoea. Examination showed a non-dysmorphic girl of normal intellect with no breast development (Tanner stage B1P4A1) who was tall compared with her parents: height standard deviation score (SDS) +1.56 vs. midparental height of +0.23 SDS, and slim build (weight −0.13 SDS). Investigations showed a 46,XX karyotype, elevated gonadotropins (FSH 119 and LH 33.7 IU/L), serum estradiol <5 pmol/L, uterine length 3.75 cm with cylindrical shape, and absent ovaries on ultrasound. Initially, a 364055-bp deletion on Xp21.2 was reported on array CGH. However, repeat analysis using BlueGnome CytoChip ISCA 4x180k v2.0 array was normal. With oral ethinyl estradiol induction puberty progressed to B4P4A2 but aged 18.4 years, the patient was remarkably tall with height SDS +2.88, weight SDS +0.97. Conclusions: Caution is needed in interpreting small changes with array CGH, particularly with the older assays. We postulate that the genetic change causing 46,XX gonadal dysgenesis in our patient may have also resulted in unsuppressed somatic growth. More critical height assessment, including parental height measurement, of future patients with 46,XX gonadal dysgenesis is recommended in order to determine whether or not a true association with tall stature may be present in certain cases.

scholarly journals 46,XY Disorder of Sex Development Caused by 17α-Hydroxylase/17,20-Lyase Deficiency due to Homozygous Mutation ofCYP17A1Gene: Consequences of Late Diagnosis

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Giampaolo Papi ◽  
Rosa Maria Paragliola ◽  
Paola Concolino ◽  
Carlo Di Donato ◽  
Alfredo Pontecorvi ◽  
...  
Keyword(s):  
Ethinyl Estradiol ◽  
Tanner Stage ◽  
Pubic Hair ◽  
Breast Development ◽  
Normal Male ◽  
Primary Amenorrhea ◽  
Homozygous Mutation ◽  
Tall Stature ◽  
Disorder Of Sex Development ◽  
Sex Development

Context.Congenital adrenal hyperplasia (CAH) is an autosomal recessive disease due to specific enzyme deficiencies in the adrenal steroidogenesis pathway.Case Description.A 40-year-old Chinese woman was referred to the Endocrine Unit for the work-up of a syndrome characterized by long-lasting and multidrug resistant high blood pressure, severe hypokalemia with metabolic alkalosis, and primary amenorrhea. The patient presented with sexual infantilism, lack of breast development, absence of axillary and pubic hair, tall stature, and slenderness. CT scan revealed enlarged adrenal glands bilaterally and the absence of the uterus, the ovaries, and the Fallopian tubes. Furthermore, diffuse osteopenia and osteoporosis and incomplete ossification of the growth plate cartilages were demonstrated. Chromosomal analysis showed a normal male 46,XY, karyotype, and on molecular analysis of theCYP17A1gene she resulted homozygous for the g.4869T>A; g.4871delC (p.Y329Kfs?) mutation in exon 6. Hydrocortisone and ethinyl-estradiol supplementation therapy led to incomplete withdrawal of antihypertensive drug and breast development progression to Tanner stage B2 and slight height increase, respectively.Conclusions.We describe a late-discovered case of CAH with 46,XY disorder of sex development. Deficiency of 17α-hydroxylase/17,20-lyase due to a homozygous CYP17A1 gene mutation was the underlying cause. Laboratory, imaging, and genetic features are herein reported and discussed.

scholarly journals Bilateral Phyllodes Giant Tumor. A Case Report Analyzed by Array-CGH

Diagnostics ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 825
Author(s):  
Francesco Fortarezza ◽  
Federica Pezzuto ◽  
Gerardo Cazzato ◽  
Clelia Punzo ◽  
Antonio d’Amati ◽  
...  
Keyword(s):  
Array Cgh ◽  
Phyllodes Tumor ◽  
Molecular Classification ◽  
Left Breast ◽  
Comparative Genomic ◽  
Fish Analysis ◽  
Molecular Tests ◽  
Giant Tumor ◽  
Metastatic Risk ◽  
The Right

The breast phyllodes tumor is a biphasic tumor that accounts for less than of 1% of all breast neoplasms. It is classified as benign, borderline, or malignant, and can mimic benign masses. Some recurrent alterations have been identified. However, a precise molecular classification of these tumors has not yet been established. Herein, we describe a case of a 43-year-old woman that was admitted to the emergency room for a significant bleeding from the breast skin. A voluminous ulcerative mass of the left breast and multiple nodules with micro-calcifications on the right side were detected at a physical examination. A left total mastectomy and a nodulectomy of the right breast was performed. The histological diagnosis of the surgical specimens reported a bilateral giant phyllodes tumor, showing malignant features on the left and borderline characteristics associated with a fibroadenoma on the right. A further molecular analysis was carried out by an array-Comparative Genomic Hybridization (CGH) to characterize copy-number alterations. Many losses were detected in the malignant mass, involving several tumor suppressor genes. These findings could explain the malignant growth and the metastatic risk. In our study, genomic profiling by an array-CGH revealed a greater chromosomal instability in the borderline mass (40 total defects) than in the malignant (19 total defects) giant phyllodes tumor, reflecting the tumor heterogeneity. Should our results be confirmed with more sensitive and specific molecular tests (DNA sequencing and FISH analysis), they could allow a better selection of patients with adverse pathological features, thus optimizing and improving patient’s management.

Tall Stature and Gonadal Dysgenesis in a Non-Mosaic Girl 45,X

2010 ◽  
Vol 73 (3) ◽  
pp. 210-214 ◽  
Author(s):  
Rosa Fernandez ◽  
Eduardo Pasaro
Keyword(s):  
Gonadal Dysgenesis ◽  
Tall Stature

scholarly journals An Unusual Presentation of 46,XY Pure Gonadal Dysgenesis: Spontaneous Breast Development and Menstruation

2015 ◽  
Vol 7 (2) ◽  
pp. 159-162 ◽  
Author(s):  
Gönül Çatlı ◽  
Caner Alparslan ◽  
P. Şule Can ◽  
Sinem Akbay ◽  
Sefa Kelekçi ◽  
...  
Keyword(s):  
Gonadal Dysgenesis ◽  
Unusual Presentation ◽  
Breast Development

A Chinese case of X-linked acrogigantism and systemic review

2020 ◽  
Author(s):  
Hanting Liang ◽  
Fengying Gong ◽  
Zhihui Liu ◽  
Yingying Yang ◽  
Yong Yao ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Web Of Science ◽  
Standard Deviation Score ◽  
Systemic Review ◽  
Maximum Diameter ◽  
Comparative Genomic ◽  
Facial Features ◽  
Chinese Case ◽  
Pituitary Enlargement ◽  
Magnetic Resonance Imaging Mri

Introduction: To describe a Chinese case of X-linked acrogigantism (X-LAG) and summarize the characteristics and treatment of all reported cases. Methods: Clinical materials and biological samples from a 5-year and 2-month-old female due to “growth acceleration for 4 years” were collected. Array comparative genomic hybrid (aCGH) and further verification were performed. All X-LAG cases from the PubMed and Web of Science databases were collected and summarized using available data. Results: The patient presented accelerating growth since 1 year of age, and her height reached 134.6 cm (+5.24 standard deviation score, SDS) when she was 5 years and 2 months old. She also had coarsening facial features, snoring, and acral enlargement. Growth hormone (GH) was not suppressed by the glucose-GH inhibition test, and insulin-like growth factor 1 (IGF-1) and prolactin levels were elevated. Pituitary magnetic resonance imaging (MRI) revealed a pituitary enlargement with a maximum diameter of 22.3 mm. Octreotide imaging indicated the presence of a pituitary adenoma. The tumor shrank slightly after three courses of somatostatin analog but without clinical or biochemical remissions, of which the GH nadir value was 9.4 ng/ml, and IGF-1 was elevated to 749 ng/ml. Therefore, she underwent transsphenoidal surgery. Immunohistochemistry showed GH-positive and PRL-positive cells in the pituitary adenoma. Xq26.3 microduplication of the patient’s germline DNA was identified by aCGH. Of all 35 reported cases, females accounted for 71.43%. There were 93.10% and 53.83% patients with hyperprolactinemia and hyperinsulinemia, respectively. Pathology showed that 75.00% of cases were adenomas. Ninety percent of cases had germline variants. The clinical and biochemical remission rates were 78.26% and 82.61%, respectively. However, the rate of complication occurrence during therapy reached 80%. Conclusion: It is important to recognize the possibility of X-LAG when a child under 2 years old presents overgrowth. Early diagnosis and treatment are of great importance for better treatment efficacy and clinical outcome.

Development and Implementation of an Analysis Tool for Array-based Comparative Genomic Hybridization

2007 ◽  
Vol 46 (05) ◽  
pp. 608-613 ◽  
Author(s):  
M. Rosolowski ◽  
H. Berger ◽  
C. Schwaenen ◽  
S. Wessendorf ◽  
M. Loeffler ◽  
...  
Keyword(s):  
Gene Expression ◽  
Comparative Genomic Hybridization ◽  
Gene Expression Data ◽  
Array Cgh ◽  
Comparative Genomic ◽  
Analysis Tool ◽  
Expression Data ◽  
Mrna Gene ◽  
Mrna Gene Expression ◽  
Chip Analysis

Summary Objectives: Array-comparative genomic hybridization (aCGH) is a high-throughput method to detect and map copy number aberrations in the genome. Multi-step analysis of high-dimensional data requires an integrated suite of bioinformatic tools. In this paperwe detail an analysis pipeline for array CGH data. Methods: We developed an analysis tool for array CGH data which supports single and multi-chip analyses as well as combined analyses with paired mRNA gene expression data. The functions supporting relevant steps of analysis were implemented using the open source software R and combined as package aCGHPipeline. Analysis methods were illustrated using 189 CGH arrays of aggressive B-cell lymphomas. Results: The package covers data input, quality control, normalization, segmentation and classification. For multi-chip analysis aCGHPipeline offers an algorithm for automatic delineation of recurrent regions. This task was performed manuallyup to now. The package also supports combined analysis with mRNA gene expression data. Outputs consist of HTML documents to facilitate communication with clinical partners. Conclusions: The R package aCGHPipeline supports basic tasks of single and multi-chip analysis of array CGH data.

P718Genome-wide copy number profiling of atherosclerotic plaques

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A Sleptcov ◽  
M S Nazarenko ◽  
A N Kazantsev ◽  
N N Burkov ◽  
N A Skryabin ◽  
...  
Keyword(s):  
Coronary Arteries ◽  
Array Cgh ◽  
Comparative Genomic ◽  
Control Group ◽  
Atherosclerotic Plaques ◽  
Cellular Interactions ◽  
Genomic Alterations ◽  
Structural Genomic ◽  
Atherosclerotic Process ◽  
In Cells

Abstract Background Atherosclerotic plaque formation results from complex cellular interactions in the intima of arteries, which take place between resident cells of the vessel wall (smooth muscle cells (SMC) and endothelial cells) and cells of the immune system (macrophages (MF)). Less well known is the genomic alterations in cells involving in the atherosclerotic process as can be important in plaque progression and instability. Aim The main purpose of the study is to assess the spectrum of structural genomic alterations in the tissue of atherosclerotic artery wall and to evaluate of difference between structural variants (SV) in SMC and MF. Materials and methods Samples of atherosclerotic plaques of the internal carotid artery (ICA) was collected from patients during endarterectomy (n=100) and the atherosclerotic coronary arteries (ACA) was obtained by coronary artery bypass surgery (n=10, group: bpACA) and by autopsy (n=8, apACA). Specimens were stored in liquid nitrogen. White blood cells (WBC) derived from the same patients. Control group was the health persons with same age (WBC, n=100). The genomic imbalances in bpACA were assessed by array comparative genomic hybridization (array-CGH, CGH Microarray 2x400K). Identified SVs was verified by droplet-digital PCR using TaqMan-assays (reference assay is RNAse P) in bpACA and ICA groups.SMC and MF were immunostained (Anti-Human CD68 Antibody and Alpha-SMA Antibody) and collected by laser capture microdissection of fresh frozen apACA samples (30–40 cells of each per sample). Collected cells were lysed and DNA amplified by whole genome amplification technique along with WBC of the same person, then analyzed by array-CGH. Results We found 90 SV in atherosclerotic coronary arteries, 13% of them were no mentioned before in Database of Genomic Variants. We selected interested SVs that contains only one gene (ACACB, ABCC9, ERLIN1, SFMBT1, PRKRA, and SIRPB1). The loss in the 3p21.1 region (SFMBT1) was in 11.48% patients and 8.5% in control group. Among patients who had diabetes mellitus (DM2) had more frequently loss of SFMBT1 (16%) than patients without DM2 (8%). The frequency of gain 2q31.2 (PRKRA) was 6% in patients whereas in control group we identified it in only one person. The frequency of loss 20p13 (SIRPB1) was approx. 67% in both groups. Several aneuploidies were found in MF (9 trisomies and 3 monosomies) and SMCs (1 trisomy and 8 monosomies). In two patients, SMCs had a normal karyotype. The ratio of duplications and deletions in MF and SMCs was 1:0.8 and 1:7, respectively. In MF of 6 patients identified same duplication in chromosome region 9q34.13-q34.2, (arr[hg19] 9q34.13(9:134337452-135931774)x3) about 2Mb in size. Conclusion Our study indicates that genomic alterations are diverse in their structure and are widely represented in cells involved in the atherosclerotic process.

scholarly journals Analysis of Array-CGH Data Using the R and Bioconductor Software Suite

2009 ◽  
Vol 2009 ◽  
pp. 1-8 ◽  
Author(s):  
Winfried A. Hofmann ◽  
Anja Weigmann ◽  
Marcel Tauscher ◽  
Britta Skawran ◽  
Tim Focken ◽  
...  
Keyword(s):  
Array Cgh ◽  
Molecular Genetic ◽  
Comparative Genomic ◽  
Accurate Identification ◽  
Genome Wide ◽  
Versatile Tool ◽  
Breakpoint Detection ◽  
Dna Copy Number Alterations ◽  
User Friendly

Background. Array-based comparative genomic hybridization (array-CGH) is an emerging high-resolution and high-throughput molecular genetic technique that allows genome-wide screening for chromosome alterations. DNA copy number alterations (CNAs) are a hallmark of somatic mutations in tumor genomes and congenital abnormalities that lead to diseases such as mental retardation. However, accurate identification of amplified or deleted regions requires a sequence of different computational analysis steps of the microarray data.Results. We have developed a user-friendly and versatile tool for the normalization, visualization, breakpoint detection, and comparative analysis of array-CGH data which allows the accurate and sensitive detection of CNAs.Conclusion. The implemented option for the determination of minimal altered regions (MARs) from a series of tumor samples is a step forward in the identification of new tumor suppressor genes or oncogenes.

High Resolution Screening of Genomic Aberrations in Follicular Lymphoma Using Microarray Based Comparative Genomic Hybridization (MATRIX-CGH).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2271-2271
Author(s):  
Carsten Schwaenen ◽  
Swen Wessendorf ◽  
Andreas Viardot ◽  
Sandra Ruf ◽  
Martina Enz ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Clinical Data ◽  
Array Cgh ◽  
Screening Method ◽  
Comparative Genomic ◽  
Rapid Progression ◽  
Human Beings ◽  
Data Set ◽  
Term Survival ◽  
Genomic Aberrations

Abstract Follicular Lymphoma (FL), one of the most frequent lymphoma entities in the western world, is characterized by a highly variable clinical course reaching from rapid progression with fatal outcome to cases with long term survival. In a recent study applying chromosomal comparative hybridization (CGH) to FL, in 70% of the cases genomic aberrations were detectable and a loss of genomic material on chromosomal bands 6q25-q27 was the strongest predictor for short overall survival. However, limitations of CGH as a screening method are a restricted genomic resolution to 3–10 Mbp and demanding non-automated evaluation procedures. Thus, high throughput analysis of genomic alterations for risk adapted patient stratification and monitoring within treatment trials should rely on efficient and automated diagnostic techniques. In this study, we used array CGH to a novel generation of DNA Chips containing 2800 genomic DNA probes. Target clones comprised i) contigs mapping to genomic regions of possible pathogenetic relevance in lymphoma (n=610 target clones mapping to e.g. 1p, 2p, 3q, 7q, 9p, 11q, 12q, 13q, 17p, 18q, X); ii) selected oncogenes and tumor suppressor genes (n=686) potentially relevant in hematologic neoplasms; and iii) a large genome-wide cluster of 1502 target DNA clones covering the genome at a distance of app. 2 Mbp (part of the golden path clone set). This chip represents a median genomic resolution of app. 1.5 Mbp. In total, DNAs from 70 FL samples were analyzed and results were compared to data from chromosomal CGH experiments and clinical data sets. The sensitivity of array CGH was considerably higher compared to chromosomal CGH (aberrations in 95% of cases vs 70% of cases). Most frequent aberrations were gain mapping to chromosome arms 2p (21%), 7p (24%), 7q (30%), 12p (17%), 12q (21%), 18p (21%) and 18q (34%) as well as losses mapping to chromosome arms 1p (19%), 6q (23%), 7p (20%), 11q (26%) and 17p (20%). In addition, several genomic aberrations were identified which have not been described before in FL. Currently, these aberrations are characterized in more detail and results will be correlated with the clinical data set. Moreover, three recurrent sites of genomic polymorphisms in human beings affecting chromosomes 5q, 14q and 15q were identified. In conclusion, these data underline the potential of array CGH for the sensitive detection of genomic imbalances in FL.

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