High throughput mutation screening of the factor VIII gene (F8C) in hemophilia A: 37 novel mutations and genotype-phenotype correlation

2002 ◽  
Vol 20 (4) ◽  
pp. 267-274 ◽  
Author(s):  
Michael Citron ◽  
Lynn Godmilow ◽  
Tapan Ganguly ◽  
Arupa Ganguly
Keyword(s):  
Factor Viii ◽  
High Throughput ◽  
Hemophilia A ◽  
Mutation Screening ◽  
Phenotype Correlation ◽  
Factor Viii Gene ◽  
Novel Mutations ◽  
Genotype Phenotype Correlation

scholarly journals Novel mutations of RPGR in Chinese families with X-linked retinitis pigmentosa

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Zhimeng Zhang ◽  
Hehua Dai ◽  
Lei Wang ◽  
Tianchang Tao ◽  
Jing Xu ◽  
...  
Keyword(s):  
Retinitis Pigmentosa ◽  
Mutation Screening ◽  
Phenotype Correlation ◽  
Novel Mutations ◽  
Pathological Myopia ◽  
Nonsense Mutations ◽  
Chinese Families ◽  
Coding Regions ◽  
Genotype Phenotype Correlation ◽  
Male Patients

Abstract Background RP (retinitis pigmentosa) is a group of hereditary retinal degenerative diseases. XLRP is a relatively severe subtype of RP. Thus, it is necessary to identify genes and mutations in patients who present with X-linked retinitis pigmentosa. Methods Genomic DNA was extracted from peripheral blood. The coding regions and intron-exon boundaries of the retinitis pigmentosa GTPase regulator (RPGR) and RP2 genes were amplified by PCR and then sequenced directly. Ophthalmic examinations were performed to identify affected individuals from two families and to characterize the phenotype of the disease. Results Mutation screening demonstrated two novel nonsense mutations (c.1541C > G; p.S514X and c.2833G > T; p.E945X) in the RPGR gene. The clinical manifestation of family 1 with mutations in exon 13 was mild. Genotype-phenotype correlation analysis suggested that patients with mutations close to the downstream region of ORF15 in family 2 manifested an early loss of cone function. Family 2 carried a nonsense mutation in ORF15 that appeared to have a semi-dominant pattern of inheritance. All male patients and two female carriers in family 2 manifested pathological myopia (PM), indicating that there may be a distinctive X-linked genotype-phenotype correlation between RP and PM. Conclusions We identified two novel mutations of the RPGR gene, which broadens the spectrum of RPGR mutations and the phenotypic spectrum of the disease in Chinese families.

scholarly journals TWO NOVEL MUTATIONS IN SIX EXONS OF FACTOR VIII GENE IN SUDANESE PATIENTS WITH HEMOPHILIA A.

2016 ◽  
Vol 4 (11) ◽  
pp. 1268-1274
Author(s):  
Dr.Wedelbahar H.Aballah ◽  
◽  
Dr.MariaM. Satti ◽  
Dr.MansourM. Mansoor ◽  
◽  
...  
Keyword(s):  
Factor Viii ◽  
Hemophilia A ◽  
Factor Viii Gene ◽  
Novel Mutations

scholarly journals Identification of the Intron 22 and Intron 1 Inversions of the Factor VIII Gene in Iraqi Kurdish Patients With Hemophilia A

2020 ◽  
Vol 26 ◽  
pp. 107602961988829 ◽  
Author(s):  
Aveen M. Raouf Abdulqader ◽  
Ali Ibrahim Mohammed ◽  
Shwan Rachid ◽  
Peyman Ghoraishizadeh ◽  
Sarwar Noori Mahmood
Keyword(s):  
Factor Viii ◽  
Hemophilia A ◽  
Causative Mutation ◽  
Coagulation Disorder ◽  
Phenotype Correlation ◽  
Factor Viii Gene ◽  
Intron 1 ◽  
Pcr Method ◽  
Polymerase Chain ◽  
And Inversion

Hemophilia A (HA) is a severe coagulation disorder affecting 1 in 5000 to 10 000 male births. In severe cases, the most deleterious large DNA rearrangements are inversions of intron 22 (Inv22) and intron 1 (Inv1) of the factor VIII (FVIII) gene. These account for 40% to 50% and 1% to 5% of all causative mutations, respectively. Nevertheless, no genetic analysis to identify the actual causative mutation of FVIII, particularly Inv22 and Inv1, among Iraqi Kurdish hemophiliacs has been performed. In this study, we aimed to genotype Inv22 and Inv1 of the FVIII gene in our patients with HA and reveal the genotype/phenotype correlation with the inversion mutations and their role as a risk factor for the development of inhibitors. Analyses of the Inv22 and Inv1 mutations in 80 Iraqi Kurdish patients with HA (60 severe, 18 moderate, and 2 mild) were performed using the inverse shifting–polymerase chain reaction (IS-PCR) method. In severe cases, 46.7% (28/60) had Inv22 and 3.3% (2/60) had Inv1. The genotype/phenotype relation of Inv22 and Inv1 illustrated a statistically significant association ( P = .012) between disease severity and inversion mutations. Slightly more patients with Inv22 (39%) developed inhibitors than those without Inv22 (28%; odds ratio = 1.65, 95% confidence interval = 0.56-4.87, P = .361). Inv22 is a major cause of severe HA in Iraqi Kurdish patients, and IS-PCR is a rapid, robust, and effective method that can be applied for carrier detection and prenatal diagnosis of HA in developing countries.

THE RELATIVE EFFICACY OF GENETIC ANALYSIS AND COAGULATION TESTING IN THE DIAGNOSIS OF CARRIERS OF HEMOPHILIA A

1987 ◽  
Author(s):  
D Lillicrap ◽  
A R Giles ◽  
J J A Holden ◽  
B N White
Keyword(s):  
Factor Viii ◽  
Gene Deletion ◽  
Hemophilia A ◽  
Fragment Length Polymorphism ◽  
Genetic Diagnosis ◽  
Prior History ◽  
Carrier Status ◽  
Factor Viii Gene ◽  
Coagulation Testing ◽  
History Of

This study has assessed the relative benefits of restriction fragment length polymorphism (RFLP) linkage and coagulation testing in the diagnosis of carriers of hemophilia A. 221 samples from 55 families have been studied for intragenic and flanking RFLPs. All samples were tested for the Factor VIII intragenic Bell RFLP and for the flanking marker St 14. 83% of obligate carrier females were heterozygous at oneor both of these two polymorphicsites. However, only38% of these women were heterozygous at the intragenic site and might safely be offered prenatal diagnosis using this marker for the hemophilia mutation. Carrier diagnosis was obtained in 52% of 81 potential carriers tested. Diagnosis wasbased on intragenic RFLP information in only 48% of these cases. Genetic diagnosis was possible in 27 atrisk women from families with no prior history of hemophilia. Four of these women were diagnosed as carriers on the basis of a gross Factor VIII gene deletion and the remaining 23 women were identified as non-carriers by the Bell (11) and Stl4 (12) RFLP data. 39 women remained undiagnosed after gene analysis studies. 23 of these women were female relatives of sporadic hemophiliacs and thus RFLP segregation analysis was inappropriate. A further 9 potential carriers were undiagnosed because of homozygosity in key individuals in their families. In 31 potential carriers we have quantitated Factor VIII:C (one stage assay) and vWf:Ag (Laurell and ELISA) and derived probabilities for carrier status. In 3 women there was conflicting genetic and coagulation data. Meanwhile, in 12 undiagnosed women from sporadic families, carrier diagnostic probabilities of > 0.9 were obtained. These studies indicate that optimal carrier detection for hemophilia A requires more intragenic and closely linked RFLPs and the continuance of coagulation testing to assist women from sporadic families.

Localization and Characterization of Mutations Within the Factor VIII Gene in a Cohort of 212 Patients with Hemophilia A

2001 ◽  
pp. 270-272
Author(s):  
J. Schröder ◽  
V. Ivaskevicius ◽  
S. Rost ◽  
A. Müller ◽  
H.-H. Brackmann ◽  
...  
Keyword(s):  
Factor Viii ◽  
Hemophilia A ◽  
Factor Viii Gene
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