X-chromosome inactivation in female patients with Fabry disease

2015 ◽  
Vol 89 (1) ◽  
pp. 44-54 ◽  
Author(s):  
L. Echevarria ◽  
K. Benistan ◽  
A. Toussaint ◽  
O. Dubourg ◽  
A.A. Hagege ◽  
...  
Keyword(s):  
Fabry Disease ◽  
X Chromosome ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation ◽  
Female Patients

scholarly journals X-chromosome inactivation patterns in females with Fabry disease examined by both ultra-deep RNA sequencing and methylation-dependent assay

2020 ◽  
Author(s):  
Rini Rossanti ◽  
Kandai Nozu ◽  
Atsushi Fukunaga ◽  
China Nagano ◽  
Tomoko Horinouchi ◽  
...  
Keyword(s):  
Fabry Disease ◽  
Rna Sequencing ◽  
X Chromosome ◽  
Clinical Symptoms ◽  
Wide Spectrum ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation ◽  
Severe Phenotype ◽  
Female Patients ◽  
Pathogenic Variants

Abstract Background: Fabry disease is an X-linked inherited lysosomal storage disorder related to GLA mutations, gene encoding α-galactosidase A. In general, males has severe phenotype, while females has a wide spectrum of sign and symptoms, from asymptomatic to a more classical profile including cardiac, renal, and cerebrovascular manifestations. This variability has been assumed to be derived from organ-dependent skewed X-chromosome inactivation (XCI) patterns in each female patient. Some previous studies examined this correlation using the classical methylation-dependent method; however, conflicting results were obtained. This study was established to determine the existence of skewed XCI in nine females with heterozygous pathogenic variants in the GLA gene and its relationship to the phenotypes. Methods: We present five female patients from one family and four individual female patients with Fabry disease. In all cases, heterozygous pathogenic variants in the GLA gene were detected. The X-chromosome inactivation patterns in peripheral blood leukocytes and cells of urine sediment were determined by both classical methylation-dependent HUMARA assay and ultra-deep RNA sequencing, the latter being a method that we recently developed. Results: Among all cases, skewed XCI resulting in predominant inactivation of the normal allele was observed only in one individual case with a severe phenotype. In the other eight cases, no skewing was observed, even among cases with severe phenotypes. Conclusions: We conclude that skewed XCI could explain the severity of Fabry disease in only a limited number of female cases and is not the main factor in the onset of various clinical symptoms in females with Fabry disease.

scholarly journals X Chromosome Inactivation in Carriers of Fabry Disease: Review and Meta-Analysis

2021 ◽  
Vol 22 (14) ◽  
pp. 7663
Author(s):  
Emanuela Viggiano ◽  
Luisa Politano
Keyword(s):  
Fabry Disease ◽  
X Chromosome ◽  
Cardiac Involvement ◽  
Clinical Symptoms ◽  
Meta Analysis ◽  
Corneal Dystrophy ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation ◽  
The North ◽  
Kidney Involvement

Anderson-Fabry disease is an X-linked inborn error of glycosphingolipid catabolism caused by a deficiency of α-galactosidase A. The incidence ranges between 1: 40,000 and 1:117,000 of live male births. In Italy, an estimate of incidence is available only for the north-western Italy, where it is of approximately 1:4000. Clinical symptoms include angiokeratomas, corneal dystrophy, and neurological, cardiac and kidney involvement. The prevalence of symptomatic female carriers is about 70%, and in some cases, they can exhibit a severe phenotype. Previous studies suggest a correlation between skewed X chromosome inactivation and symptoms in carriers of X-linked disease, including Fabry disease. In this review, we briefly summarize the disease, focusing on the clinical symptoms of carriers and analysis of the studies so far published in regards to X chromosome inactivation pattern, and manifesting Fabry carriers. Out of 151 records identified, only five reported the correlation between the analysis of XCI in leukocytes and the related phenotype in Fabry carriers, in particular evaluating the Mainz Severity Score Index or cardiac involvement. The meta-analysis did not show any correlation between MSSI or cardiac involvement and skewed XCI, likely because the analysis of XCI in leukocytes is not useful for predicting the phenotype in Fabry carriers.

scholarly journals High frequency of the X-chromosome inactivation in young female patients with high-grade glioma

2013 ◽  
Vol 8 (1) ◽  
Author(s):  
Gang Li ◽  
Zhiguo Zhang ◽  
Tianbo Jin ◽  
Hongjuan Liang ◽  
Yanyang Tu ◽  
...  
Keyword(s):  
X Chromosome ◽  
High Frequency ◽  
High Grade Glioma ◽  
Young Female ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation ◽  
High Grade ◽  
Female Patients

scholarly journals X chromosome inactivation pattern in female patients with breast cancer

2000 ◽  
Vol 2 (S1) ◽  
Author(s):  
M Kristiansen ◽  
A Langer ◽  
GP Knudsen ◽  
BL Weber ◽  
A-L Børresen-Dale ◽  
...  
Keyword(s):  
Breast Cancer ◽  
X Chromosome ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation ◽  
Female Patients ◽  
Inactivation Pattern

scholarly journals Female Fabry disease patients and X-chromosome inactivation

Gene ◽  
2018 ◽  
Vol 641 ◽  
pp. 259-264 ◽  
Author(s):  
Patrycja Juchniewicz ◽  
Anna Kloska ◽  
Anna Tylki-Szymańska ◽  
Joanna Jakóbkiewicz-Banecka ◽  
Grzegorz Węgrzyn ◽  
...  
Keyword(s):  
Fabry Disease ◽  
X Chromosome ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation

EEC Growth, JAK2 Mutation, PRV-1 Overexpression and X-Chromosome Inactivation Pattern: Predicting Values on Polycythemia Vera Evolution and Risk of Thrombosis in Idiopathic Thrombocytosis.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2692-2692
Author(s):  
Lee-Yung Shih ◽  
Ching-Tai Lee ◽  
Tung-Liang Lin ◽  
Chia-Hui Chang ◽  
Chein-Fuang Huang ◽  
...  
Keyword(s):  
X Chromosome ◽  
Bone Marrow Cells ◽  
Vascular Complications ◽  
X Chromosome Inactivation ◽  
Initial Presentation ◽  
Chromosome Inactivation ◽  
Pcr Assay ◽  
Jak2 Mutation ◽  
Female Patients ◽  
Inactivation Pattern

Abstract We have previously demonstrated that endogenous erythroid colony (EEC) growth could predict PV evolution in idiopathic thrombocytosis (IT) (Blood 83:744, 1994). We also showed that female patients with IT and monoclonal X-chromosome inactivation pattern (XCIP) had a high risk of vascular complications (Blood100:1596, 2002). Recently, PRV-1 overexpression and JAK2V617F mutation have been described and implicated in the diagnosis of Ph(-) chronic myeloproliferative disorders. In a large cohort of patients with IT, we aimed to determine the correlation among the molecular markers of EEC growth, JAK2 mutation status, PRV-1 level and XCIP, and to assess the predicting values of these biomarkers on PV evolution and risk of thrombosis. Allele-specific PCR assay was used to detect JAK2V617F in peripheral blood granulocytes (n=178) or bone marrow cells (n=75) from patients with IT. EEC assay was performed on 235 patients in a serum-free culture system at initial diagnosis. PRV-1 mRNA expression in granulocytes from 187 patients was measured by real-time RQ-PCR assay and expressed as the copy number of PRV-1 normalized to GAPDH gene (NCN). Clonality analysis of XCIP with HUMARA-PCR assay was performed on 123 female patients. JAK2V617F was detected in 57.7% of patients with IT. Forty-one percent of IT patients had EEC growth at initial presentation. Of those analyzed for PRV-1 levels, 138 patients had not received platelet-lowering agents at time of analysis; 72 (38.5%) had PRV-1 overexpression with NCN ≥ 1 (NCN of 30 normal subjects, mean±SE: 0.32±0.04, range: 0.04–0.97). Seventy-six female patients had monoclonal XCIP and 28 had polyclonal XCIP; the remaining 19 patients had ambiguous or homozygous pattern of XCIP. EEC growth was strongly correlated with JAK2 mutation (P<0.0001) and PRV-1 overexpression (P<0.0001). PRV-1 overexpression was highly associated with JAK2 mutation (P<0.0001) and monoclonal XCIP (P=0.003). The frequency of JAK2 mutation or EEC growth was not different between monoclonal and polyclonal XCIP. Thirty-four patients subsequently developed PV (IT-PV), ranging from 1.5 months to 90 months. All 34 IT-PV patients had EEC growth and all but one harbored JAK2 mutation at initial presentation. Patients with IT-PV had a significantly higher frequency of EEC(+) (P<0.0001), JAK2(+) (P<0.0001), and PRV-1(+) (P<0.0001) than those without PV evolution, whereas there was no difference in age (P=0.914) or XCIP (P=0.550) between IT with and without PV evolution. One hundred and sixty-nine patients had all biomarkers of JAK2/EEC/PRV-1 analyzed, 57 patients were JAK2(+)/EEC(+)/PRV-1(+) and 55 were JAK2(-)/EEC(-)/PRV-1(-). Eighteen patients with all 3 biomarkers-positive developed PV later compared with none of patients with all 3 biomarkers-negative (P<0.0001). Eighty-two patients experienced thrombotic complications during their disease courses. The occurrence of thrombosis was strongly associated with EEC growth (P=0.0002), JAK2 mutation (P=0.007), PRV-1 level (P=0.004), and XCIP (P=0.034). The present study showed that EEC growth and JAK2 mutation were predictors of PV evolution; EEC growth, JAK2 mutation, PRV-1 overexpression and monoclonal XCIP predicted the risk of thrombosis in patients with IT.

scholarly journals Predictive values of X-chromosome inactivation patterns and clinicohematologic parameters for vascular complications in female patients with essential thrombocythemia

Blood ◽  
2002 ◽  
Vol 100 (5) ◽  
pp. 1596-1601 ◽  
Author(s):  
Lee-Yung Shih ◽  
Tung-Liang Lin ◽  
Chang-Liang Lai ◽  
Po Dunn ◽  
Jin-Hou Wu ◽  
...  
Keyword(s):  
X Chromosome ◽  
Essential Thrombocythemia ◽  
Receptor Gene ◽  
Vascular Complications ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation ◽  
Predictive Values ◽  
Female Patients ◽  
Increased Risk ◽  
Risk For Thrombosis

Essential thrombocythemia (ET) is a heterogeneous disorder in which the clonality of hematopoiesis varies. The clinical significance of clonality status in ET remains to be determined. We used the human androgen receptor gene (HUMARA)–polymerase chain reaction assay to investigate X-chromosome inactivation patterns (XCIPs) and their value in predicting vascular complications in 89 female patients with ET. Fifty-four (68.4%) patients had a clonal pattern of XCIP, and 15 (19.0%) had a polyclonal pattern. The remaining 20 patients had either an ambiguous or a homozygous pattern of XCIP and were therefore excluded from further analysis. Patients with clonal XCIPs were older (P = .029) and were at greater risk for thrombosis (P = .007) than were those with polyclonal XCIPs. We did not find a correlation between the occurrence of hemorrhage and XCIP (P = .492). Advanced age was predictive of thrombosis and hemorrhage. Platelet count did not influence the risk for vascular complications. Hypertension was significantly correlated with thrombotic events (P = .002), whereas diabetes mellitus and hypercholesterolemia were of no predictive value. In a multivariate analysis, age was the significant predictor of thrombosis (P = .030); however, XCIPs (P = .083) and hypertension (P = .073) tended to predict thrombosis. Our results suggest that older patients who have clonal XCIPs or hypertension are at increased risk for thrombosis and should be monitored closely for this complication.

scholarly journals Clonal patterns of X-chromosome inactivation in peripheral blood cells of female patients with chronic idiopathic neutropenia

Haematologica ◽  
2012 ◽  
Vol 97 (12) ◽  
pp. 1931-1933 ◽  
Author(s):  
S. Mastrodemou ◽  
V. Vazgiourakis ◽  
M. Velegraki ◽  
K. Pavlaki ◽  
G. N. Goulielmos ◽  
...  
Keyword(s):  
X Chromosome ◽  
Peripheral Blood ◽  
Blood Cells ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation ◽  
Peripheral Blood Cells ◽  
Female Patients ◽  
Chronic Idiopathic Neutropenia
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