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Title: Somatic mosaicism and female-to-female transmission in a kindred with hemophilia B (factor IX deficiency)

Abstract

Studies have shown that hemophilia B (Christmas disease; factor IX deficiency) results from many different mutations in the factor IX gene, of which {gt}95% are single nulceotide substitutions. This study has identified a previously unreported form of hemophilia B in a patient who was a somatic mosaic for a guanine-to-cytosine transversion at nucleotide 31,170 in the factor IX gene. This point mutation changes the codon for residue 350 in the catalytic domain of factor IX from a cysteine to a serine. The authors used differential termination of primer extension to confirm and measure the degree of mosaicism. The study shows that a varying proportion of cells from hepatic, renal, smooth muscle, and hematopoietic populations possessed normal as well as mutant factor IX sequences. These results indicate that the mutation in this patient occurred either as an uncorrected half-chromatid mutation in the female gamete or as a replication or postreplication error in the initial mitotic divisions of the zygote preceding implantation. In addition, this kindred also contains two females in successive generations who have moderately severe factor IX deficiency. The molecular pathogenesis of this latter phenomenon has been studied and seems to relate to the unaccompanied expression of the mutant factormore » IX gene consequent upon a second, as yet undefined, genetic event that has prevented inactivation of sequences including the mutant factor IX gene on the X chromosome inherited from the affected male.« less

Authors:
; ;  [1]
  1. (Queen's Univ., Kingston, Ontario (Canada))
Publication Date:
OSTI Identifier:
5079758
Resource Type:
Journal Article
Resource Relation:
Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (United States); Journal Volume: 88:1
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; DNA; AUTORADIOGRAPHY; GENE MUTATIONS; DNA SEQUENCING; HEMOPHILIA; MOLECULAR BIOLOGY; DNA BASE TRANSITIONS; HEREDITARY DISEASES; PATIENTS; DISEASES; HEMIC DISEASES; MUTATIONS; NUCLEIC ACIDS; ORGANIC COMPOUNDS; STRUCTURAL CHEMICAL ANALYSIS; 550201* - Biochemistry- Tracer Techniques

Citation Formats

Taylor, S.A.M., Deugau, K.V., and Lillicrap, D.P.. Somatic mosaicism and female-to-female transmission in a kindred with hemophilia B (factor IX deficiency). United States: N. p., 1991. Web. doi:10.1073/pnas.88.1.39.
Taylor, S.A.M., Deugau, K.V., & Lillicrap, D.P.. Somatic mosaicism and female-to-female transmission in a kindred with hemophilia B (factor IX deficiency). United States. doi:10.1073/pnas.88.1.39.
Taylor, S.A.M., Deugau, K.V., and Lillicrap, D.P.. Tue . "Somatic mosaicism and female-to-female transmission in a kindred with hemophilia B (factor IX deficiency)". United States. doi:10.1073/pnas.88.1.39.
@article{osti_5079758,
title = {Somatic mosaicism and female-to-female transmission in a kindred with hemophilia B (factor IX deficiency)},
author = {Taylor, S.A.M. and Deugau, K.V. and Lillicrap, D.P.},
abstractNote = {Studies have shown that hemophilia B (Christmas disease; factor IX deficiency) results from many different mutations in the factor IX gene, of which {gt}95% are single nulceotide substitutions. This study has identified a previously unreported form of hemophilia B in a patient who was a somatic mosaic for a guanine-to-cytosine transversion at nucleotide 31,170 in the factor IX gene. This point mutation changes the codon for residue 350 in the catalytic domain of factor IX from a cysteine to a serine. The authors used differential termination of primer extension to confirm and measure the degree of mosaicism. The study shows that a varying proportion of cells from hepatic, renal, smooth muscle, and hematopoietic populations possessed normal as well as mutant factor IX sequences. These results indicate that the mutation in this patient occurred either as an uncorrected half-chromatid mutation in the female gamete or as a replication or postreplication error in the initial mitotic divisions of the zygote preceding implantation. In addition, this kindred also contains two females in successive generations who have moderately severe factor IX deficiency. The molecular pathogenesis of this latter phenomenon has been studied and seems to relate to the unaccompanied expression of the mutant factor IX gene consequent upon a second, as yet undefined, genetic event that has prevented inactivation of sequences including the mutant factor IX gene on the X chromosome inherited from the affected male.},
doi = {10.1073/pnas.88.1.39},
journal = {Proceedings of the National Academy of Sciences of the United States of America; (United States)},
number = ,
volume = 88:1,
place = {United States},
year = {Tue Jan 01 00:00:00 EST 1991},
month = {Tue Jan 01 00:00:00 EST 1991}
}