Unusual X chromosome inactivation in a mentally retarded girl with an interstitial deletion Xq27: implications for the fragile X syndrome

1990 ◽  
Vol 84 (4) ◽  
pp. 347-352 ◽  
Author(s):  
Malgorzata Schmidt ◽  
Andrea Certoma ◽  
Desirée Du Sart ◽  
Paul Kalitsis ◽  
Margaret Leversha ◽  
...  
Keyword(s):  
Fragile X Syndrome ◽  
X Chromosome ◽  
Fragile X ◽  
Mentally Retarded ◽  
X Chromosome Inactivation ◽  
Interstitial Deletion ◽  
Chromosome Inactivation

scholarly journals Detection of skewed X-chromosome inactivation in Fragile X syndrome and X chromosome aneuploidy using quantitative melt analysis

2015 ◽  
Vol 17 ◽  
Author(s):  
David E. Godler ◽  
Yoshimi Inaba ◽  
Charles E. Schwartz ◽  
Quang M. Bui ◽  
Elva Z. Shi ◽  
...  
Keyword(s):  
Fragile X Syndrome ◽  
X Chromosome ◽  
Sex Chromosome ◽  
Fragile X ◽  
Venous Blood ◽  
Reference Method ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation ◽  
X Chromosomes ◽  
Skewed X Chromosome Inactivation

Methylation of the fragile X mental retardation 1 (FMR1) exon 1/intron 1 boundary positioned fragile X related epigenetic element 2 (FREE2), reveals skewed X-chromosome inactivation (XCI) in fragile X syndrome full mutation (FM: CGG > 200) females. XCI skewing has been also linked to abnormal X-linked gene expression with the broader clinical impact for sex chromosome aneuploidies (SCAs). In this study, 10 FREE2 CpG sites were targeted using methylation specific quantitative melt analysis (MS-QMA), including 3 sites that could not be analysed with previously used EpiTYPER system. The method was applied for detection of skewed XCI in FM females and in different types of SCA. We tested venous blood and saliva DNA collected from 107 controls (CGG < 40), and 148 FM and 90 SCA individuals. MS-QMA identified: (i) most SCAs if combined with a Y chromosome test; (ii) locus-specific XCI skewing towards the hypomethylated state in FM females; and (iii) skewed XCI towards the hypermethylated state in SCA with 3 or more X chromosomes, and in 5% of the 47,XXY individuals. MS-QMA output also showed significant correlation with the EpiTYPER reference method in FM males and females (P < 0.0001) and SCAs (P < 0.05). In conclusion, we demonstrate use of MS-QMA to quantify skewed XCI in two applications with diagnostic utility.

scholarly journals A brain network basis of Fragile X syndrome behavioral penetrance determined by X chromosome inactivation in female mice

2018 ◽  
Author(s):  
Eric Szelenyi ◽  
Danielle Fisenne ◽  
Joseph E Knox ◽  
Julie A Harris ◽  
James A Gornet ◽  
...  
Keyword(s):  
Fragile X Syndrome ◽  
Cell Density ◽  
X Chromosome ◽  
Fragile X ◽  
Mutant Cell ◽  
Autism Spectrum ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation ◽  
Entry Points ◽  
Parent Of Origin

ABSTRACTX-chromosome inactivation (XCI) in females is vital for normal brain function and cognition, as many X-linked genetic mutations lead to mental retardation and autism spectrum disorders, such as the fragile X syndrome (FXS). However, the degree by which XCI regulates disease presentation has been poorly investigated. To study this regulation in the mouse, here we quantified the brainwide composition of active-XC cells at single cell resolution using an X-linked MECP2-EGFP allele with known parent-of-origin. We present evidence that whole-brains, including all regions, on average favor maternal XC-active cells by 20%, or 8 million cells. This bias was conserved in heterozygous FXS mutant mice, which also corresponded to disease penetrance in maternal but not paternal FMR1 null mice. To localize the physical source of behavioral penetrance, brain-wide correlational screens successfully mapped mouse performance to cell densities in putative sensorimotor (e.g. sensory hindbrain, thalamus, globus pallidus) and sociability (e.g. visual/entorhinal cortices, bed nucleus stria terminalis, medial preoptic area) behavioral circuits of the open field sensorimotor and 3-chamber sociability assays, respectively. Overall, 50%/50% healthy/mutant cell density ratios in these sub-networks were required for disease presentation in each behavior. These results suggest female X-linked behavioral penetrance of disease is regulated at the distributed level of mutant cell density in behavioral circuits, which is set by XCI that is subject to parent-of-origin effects. This work provides a novel finding behind the broad and varied behavioral phenotypes commonly featured in female patients debilitated by X-linked mental disorders and may offer new entry points for behavioral therapeutics.

X chromosome inactivation does not define the development of premature ovarian failure in fragile X premutation carriers

2010 ◽  
Vol 152A (2) ◽  
pp. 387-393 ◽  
Author(s):  
Marian A. Spath ◽  
Willy N. Nillesen ◽  
Arie P.T. Smits ◽  
Ton B. Feuth ◽  
Didi D.M. Braat ◽  
...  
Keyword(s):  
X Chromosome ◽  
Premature Ovarian Failure ◽  
Fragile X ◽  
X Chromosome Inactivation ◽  
Ovarian Failure ◽  
Chromosome Inactivation ◽  
Fragile X Premutation

X-linked CNV and skewed X-chromosome inactivation

2020 ◽  
pp. 19-21
Author(s):  
Е.А. Фонова ◽  
Е.Н. Толмачева ◽  
А.А. Кашеварова ◽  
М.Е. Лопаткина ◽  
К.А. Павлова ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Intellectual Disability ◽  
X Chromosome ◽  
Copy Number ◽  
Copy Number Variations ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation ◽  
Chromosome X ◽  
Skewed X Chromosome Inactivation

Смещение инактивации Х-хромосомы может быть следствием и маркером нарушения клеточной пролиферации при вариациях числа копий ДНК на Х-хромосоме. Х-сцепленные CNV выявляются как у женщин с невынашиванием беременности и смещением инактивации Х-хромосомы (с частотой 33,3%), так и у пациентов с умственной отсталостью и смещением инактивацией у их матерей (с частотой 40%). A skewed X-chromosome inactivation can be a consequence and a marker of impaired cell proliferation in the presence of copy number variations (CNV) on the X chromosome. X-linked CNVs are detected in women with miscarriages and a skewed X-chromosome inactivation (with a frequency of 33.3%), as well as in patients with intellectual disability and skewed X-chromosome inactivation in their mothers (with a frequency of 40%).

scholarly journals X-Linked Emery–Dreifuss Muscular Dystrophy: Study Of X-Chromosome Inactivation and Its Relation with Clinical Phenotypes in Female Carriers

Genes ◽  
2019 ◽  
Vol 10 (11) ◽  
pp. 919 ◽  
Author(s):  
Viggiano ◽  
Madej-Pilarczyk ◽  
Carboni ◽  
Picillo ◽  
Ergoli ◽  
...  
Keyword(s):  
Muscular Dystrophy ◽  
X Chromosome ◽  
Clinical Symptoms ◽  
Fibrous Tissue ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation ◽  
Cardiac Conduction ◽  
Asymptomatic Carriers ◽  
Cardiac Symptoms ◽  
Female Carriers

X-linked Emery–Dreifuss muscular dystrophy (EDMD1) affects approximately 1:100,000 male births. Female carriers are usually asymptomatic but, in some cases, they may present clinical symptoms after age 50 at cardiac level, especially in the form of conduction tissue anomalies. The aim of this study was to evaluate the relation between heart involvement in symptomatic EDMD1 carriers and the X-chromosome inactivation (XCI) pattern. The XCI pattern was determined on the lymphocytes of 30 symptomatic and asymptomatic EDMD1 female carriers—25 familial and 5 sporadic cases—seeking genetic advice using the androgen receptor (AR) methylation-based assay. Carriers were subdivided according to whether they were above or below 50 years of age. A variance analysis was performed to compare the XCI pattern between symptomatic and asymptomatic carriers. The results show that 20% of EDMD1 carriers had cardiac symptoms, and that 50% of these were ≥50 years of age. The XCI pattern was similar in both symptomatic and asymptomatic carriers. Conclusions: Arrhythmias in EDMD1 carriers poorly correlate on lymphocytes to a skewed XCI, probably due to (a) the different embryological origin of cardiac conduction tissue compared to lymphocytes or (b) the preferential loss of atrial cells replaced by fibrous tissue.

scholarly journals Loss of p53 Causes Stochastic Aberrant X-Chromosome Inactivation and Female-Specific Neural Tube Defects

Cell Reports ◽  
2019 ◽  
Vol 27 (2) ◽  
pp. 442-454.e5 ◽  
Author(s):  
Alex R.D. Delbridge ◽  
Andrew J. Kueh ◽  
Francine Ke ◽  
Natasha M. Zamudio ◽  
Farrah El-Saafin ◽  
...  
Keyword(s):  
X Chromosome ◽  
Neural Tube ◽  
Neural Tube Defects ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation ◽  
Female Specific
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