Effects of X Chromosome Monosomy and Genomic Imprinting on Observational Markers of Social Anxiety in Prepubertal Girls with Turner Syndrome

Abstract Introduction Turner syndrome (TS) is caused by the absence or structural abnormality of X chromosome. Compared with the general population, the prevalence of congenital heart defects is significantly higher in women with TS, especially with 45,X karyotype. Moreover, congenital heart defects represent the major risk for aortic dissection in TS individuals. Purpose There is a lack of reliable evidence whether the extremely variable cardiovascular phenotype including presence of aortic coarctation (CoA) and bicuspid aortic valve (BAV) in TS women may be influenced by the parental origin of the retained X chromosome. Methods DNA samples were collected from peripheral lymphocytes of 48 women with non-mosaic 45,X karyotype and from buccal swab of their biological parents' cheek. Subsequently, the single normal X-chromosome origin was identified. Based on genetic evaluation, patients were divided into two subgroups according to the parenteral original of X chromosome - maternal (XM), and paternal (XP). Complete cardiovascular examination (echocardiography, MRI of the heart and great vessels) was performed in each of our study patient. Differences between the prevalence of BAV and CoA in two above mentioned subgroups were tested by Student's t-test using R Statistical Software version 2.15.3. Results The origin of the single X chromosome was as follows: in 14 (29.2%) individuals was proved paternal and in 34 (70.8%) maternal origin of X chromosome. The prevalence of BAV in the whole group was 47.9%, in XP 58%, in XM 44.1%; the prevalence of CoA in the whole group was 8.3%, in XP 7.1%, in XM 8.8%. There was no statistically significant difference identified between the prevalence of BAV and CoA in XP and XM subgroups. Conclusions Our study confirmed an extremely high prevalence of BAV and CoA in non-mosaic women with X chromosome monosomy but no clear evidence for X-linked genomic imprinting effect on the CoA and BAV development in TS individuals was found. However, further studies of larger numbers of TS patients are crucial to finally clarify the real relationship of genomic imprinting and cardiovascular disease in TS. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Supported by the grant from Ministry of Health of the Czech Republic VES 2017

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Severe haemophilia a in a preterm girl with turner syndrome - a case report from the prenatal period to early infancy (part I)

Italian Journal of Pediatrics ◽

10.1186/s13052-020-00892-7 ◽

2020 ◽

Vol 46 (1) ◽

Author(s):

Agnieszka Berendt ◽

Monika Wójtowicz-Marzec ◽

Barbara Wysokińska ◽

Anna Kwaśniewska

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Turner Syndrome ◽

X Chromosome ◽

Diagnostic Procedures ◽

Haemophilia A ◽

Severe Haemophilia ◽

Preterm Children ◽

Initial Symptoms ◽

The Central Nervous System

Abstract Background Bleedings are more frequent in the population of preterm children than among those born at term, much less in older children. The reasons for such bleedings in preterms include plasma factor deficiencies, immaturity of small vessels in the germinal matrix region, prenatal hypoxia or sepsis. They affect the brain tissue, the gastrointestinal tract and the respiratory system, or are manifested by prolonged bleedings from injection sites. Haemophilia is a rare cause of haemorrhages in the neonatal period, and in the female population it is even seen as an extremely rare disorder. Its aetiology in girls is diverse: inheriting defective genes from their parents, skewed X inactivation or a single X chromosome. Case presentation The article presents a case of a preterm girl born in the 28th week of pregnancy, who was diagnosed with severe haemophilia A stemming from the absence of the X chromosome. The girl’s father is healthy, but her mother’s brother suffers from haemophilia. On the second day of the child’s life, a prolonged bleeding from the injection site was observed. A coagulation profile revealed prolonged APTT which pointed to haemophilia A diagnosis. Moreover, a marked clinical dysmorphy, female sex and a negative family history on the father’s side led the treating team to extend the diagnostic procedures to encompass karyotype evaluation. The girl was diagnosed with Turner syndrome. No bleeding to the central nervous system was observed during her hospital stay. Conclusions Preterm children belong to the risk group of bleeding into the central nervous system or haemorrhages in the course of sepsis. Rare causes of such bleedings should also be borne in mind, including haemophilia. The initial symptoms of haemophilia in preterm children occur in the first days of their lives, which is connected with a number of invasive procedures required in that period. Genetic conditions may coexist with one another. Arriving at one diagnosis does not mean one should abandon further diagnostic procedures in cases where additional atypical symptoms are present which do not match the clinical image of a primary disease.

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The value of a simple method to decrease diagnostic errors in Turner syndrome: a case report

Journal of Medical Case Reports ◽

10.1186/s13256-021-02673-0 ◽

2021 ◽

Vol 15 (1) ◽

Author(s):

Seyedetahere Mousavi ◽

Batool Amiri ◽

Saidee Beigi ◽

Mohammadreza Farzaneh

Keyword(s):

Case Report ◽

Standard Deviation ◽

Physical Examination ◽

Turner Syndrome ◽

X Chromosome ◽

Genetic Disorder ◽

Diagnostic Errors ◽

Height Velocity ◽

Target Height ◽

Simple Method

Abstract Introduction Turner syndrome is a genetic disorder in females and is the result of complete or partial loss of an X chromosome during fertilization. The missing X chromosome is originally either from the mother's ovum or the father's sperm cell. Approximately 45% of patients have the 45,X karyotype and the rest have other variants of Turner syndrome, which are either mosaicism patterns or structural abnormalities of the X chromosome. Here, we report a case of Turner syndrome that is the fifth case of Turner syndrome with balanced Robertsonian translocation of (13;14)(q10;q10), and the sixth case with 44,X chromosomes, reported in the literature thus far. Case presentation A 10.3-year-old Persian girl was brought to our clinic by her parents, with the complaint of failure to thrive and short height. She had been examined and investigated by endocrinologists since the age of 4 years, but no definite diagnosis was made. At the time of presentation, she had been through three provocative growth hormone tests and had been on no medications for about a year. Her physical examination revealed mild retrognathia and micrognathia. Initially, she was started on somatropin treatment which, after 12 months, did not appropriately improve her height velocity. Therefore, a more thorough physical examination was performed, in which high arched palate and low posterior hairline were observed. There was also a difference between target height and patient height standard deviation scores. Karyotype study was requested, and Turner syndrome was confirmed. Conclusion The diagnosis of this case was not straightforward, both because the somatic presentations were not obvious, and because the physicians had not looked for them when performing the physical examinations. This case report introduces a rare 44,X chromosome karyotype of Turner syndrome and highlights the value in using the difference between target height and patient height standard deviation scores as a simple and inexpensive tool for diagnosis of this syndrome.

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Clinical Significance of the Parental Origin of the X Chromosome in Turner Syndrome

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2006-0158 ◽

2007 ◽

Vol 92 (3) ◽

pp. 846-852 ◽

Cited By ~ 55

Author(s):

Liora Sagi ◽

Nehama Zuckerman-Levin ◽

Aneta Gawlik ◽

Lucia Ghizzoni ◽

Atilla Buyukgebiz ◽

...

Keyword(s):

Turner Syndrome ◽

Clinical Significance ◽

X Chromosome ◽

Parental Origin

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An N-Ethyl-N-Nitrosourea Mutagenesis Screen for Epigenetic Mutations in the Mouse

Genetics ◽

10.1093/genetics/164.4.1481 ◽

2003 ◽

Vol 164 (4) ◽

pp. 1481-1494

Author(s):

Ivona Percec ◽

Joanne L Thorvaldsen ◽

Robert M Plenge ◽

Christopher J Krapp ◽

Joseph H Nadeau ◽

...

Keyword(s):

Genomic Imprinting ◽

X Chromosome ◽

X Inactivation ◽

Monoallelic Expression ◽

Chromosome 15 ◽

Chromosome 5 ◽

Chromosome 10 ◽

Mutagenesis Screen ◽

Distal Chromosome ◽

Males And Females

Abstract The mammalian epigenetic phenomena of X inactivation and genomic imprinting are incompletely understood. X inactivation equalizes X-linked expression between males and females by silencing genes on one X chromosome during female embryogenesis. Genomic imprinting functionally distinguishes the parental genomes, resulting in parent-specific monoallelic expression of particular genes. N-ethyl-N-nitrosourea (ENU) mutagenesis was used in the mouse to screen for mutations in novel factors involved in X inactivation. Previously, we reported mutant pedigrees identified through this screen that segregate aberrant X-inactivation phenotypes and we mapped the mutation in one pedigree to chromosome 15. We now have mapped two additional mutations to the distal chromosome 5 and the proximal chromosome 10 in a second pedigree and show that each of the mutations is sufficient to induce the mutant phenotype. We further show that the roles of these factors are specific to embryonic X inactivation as neither genomic imprinting of multiple genes nor imprinted X inactivation is perturbed. Finally, we used mice bearing selected X-linked alleles that regulate X chromosome choice to demonstrate that the phenotypes of all three mutations are consistent with models in which the mutations have affected molecules involved specifically in the choice or the initiation of X inactivation.

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