Variant of Factor IX Deficiency in Female with 45, X Turner’s Syndrome

Bithell, Thomas C; Pizarro, Alejandro; Macdiarmid, W. D.

doi:10.1182/blood.v36.2.169.169

Cited by 31 publications

(11 citation statements)

References 22 publications

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“…Hemophilia A or B in females is a rare occurrence. The possible causes of clinical hemophilia in females have been documented to be (1) due to homozygosity for the hemophilia gene resulting from consanguinity [2,14] or double de-novo mutations [15], (2) deletion (Turner's syndrome [16]) or structural abnormalities of the Xchromosomes [3,4,17], (3) non-random skewed inactiva-tion of the normal X-chromosome [6,7], or (4) theoretically, due to genetic homozygosity or uniparental disomy.…”

Section: Discussionmentioning

confidence: 99%

Hemophilia B in a female carrier due to skewed inactivation of the normal X-chromosome

et al. 1998

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A novel missense mutation (codon 351, GCT (Ala) --> CCT (Pro)) of the FIX gene was characterised in a young female with mild hemophilia B. She is heterozygous for the FIX mutation inherited from her carrier mother. Analysis of the methyl-sensitive Hpa II sites at the 5' end of the hypoxanthine phosphoribosyltransferase gene showed that skewed inactivation of the X chromosome carrying her normal FIX gene accounted for the hemophilia phenotype.

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Section: Discussionmentioning

confidence: 99%

Hemophilia B in a female carrier due to skewed inactivation of the normal X-chromosome

et al. 1998

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“…Such cases have been observed predominantly in females with numerical or structural abnormalities of the X chromosome. The disease is caused either by a hemizygous mutation, as seen in Turner syndrome [3], or by predominant expression of the mutated allele as a result of preferential inactivation of the normal X chromosome, carrying the wild‐type FVIII gene [4]. However, clinical manifestation of X‐linked recessive disorders has also repeatedly been reported in females without cytogenetically detectable rearrangement of the X chromosome.…”

Section: Introductionmentioning

confidence: 99%

Female haemophiliac homozygous for the factor VIII intron 22 inversion mutation, with transcriptional inactivation of one of the factor VIII alleles

et al. 2003

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Phenotypic expression of X-linked recessive disorders, including haemophilia A, is rare in females. This report describes a female with sporadic severe haemophilia A. The female patient and her family members were evaluated by coagulation assays. Visible detectable disturbance of X chromosome structure or number, as well as 2N von Willebrand disease, were excluded as possible explanations of the haemophilia A phenotype. Molecular studies, factor VIII (FVIII) intron 22 inversion mutation analysis showed that the severe haemophilia A phenotype is the result of a maternally inherited, distal, FVIII gene inversion and a paternally inherited de novo, also distal, FVIII gene inversion. Furthermore, comparative single-stranded conformation polymorphism analysis revealed the absence of detectable maternally inherited abnormal FVIII gene transcript in the patient's peripheral blood lymphocytes. X chromosome methylation analysis indicates that this could be explained by preferential inactivation of the maternally inherited X chromosome carrying the distal FVIII gene inversion.

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“…For instance, structural chromosomal abnormalities such as translocations are known to result in nonrandom X chromosomal inactivation in female carriers ( Mori et al , 1979 ; Spinelli et al , 1976 ; Gilgenkrantz et al , 1986 ). Homozygosity for the recessive allele, iso(X) chromosome or Turner syndrome have been found in other cases ( Bithell et al , 1970 ; Lusher & McMillan, 1978; Panarello et al , 1992 ).…”

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A de novo translocation 46,X,t(X;15) causing haemophilia B in a girl: a case report

et al. 1998

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Haemophilia B is an X-linked recessive bleeding disorder caused by mutations in the factor IX gene with an incidence of 1:25000-30000. Usually female carriers are clinically normal, and severe phenotypic expression of the disease in females is extremely rare. In this report we describe a girl with a clinically severe course of haemophilia B who had no signs of Turner syndrome or any other dysmorphic features. Cytogenetic and molecular studies in the patient and her parents showed a de novo translocation 46,X,t(X;15)(q27.1;p11.2) in the patient, indicating a possible break near the factor IX gene. The structurally normal X chromosome was late replicating and inactivated in all metaphases as shown by high-resolution R-banding. By fluorescence in situ hybridization (FISH) with YAC and cosmid probes we could further characterize the breakpoint region on the X chromosome and the involvement of the factor IX gene.

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Variant of Factor IX Deficiency in Female with 45, X Turner’s Syndrome

Cited by 31 publications

References 22 publications

Hemophilia B in a female carrier due to skewed inactivation of the normal X-chromosome

Hemophilia B in a female carrier due to skewed inactivation of the normal X-chromosome

Female haemophiliac homozygous for the factor VIII intron 22 inversion mutation, with transcriptional inactivation of one of the factor VIII alleles

A de novo translocation 46,X,t(X;15) causing haemophilia B in a girl: a case report

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