Advanced

Two factor IX mutations in the family of an isolated haemophilia B patient : direct carrier diagnosis by amplification mismatch detection (AMD)

Montandon, A J; Green, P M; Bentley, D R; Ljung, R LU ; Nilsson, Inga Marie and Giannelli, F (1990) In Human Genetics 85(2). p.4-200
Abstract

Rapid identification of gene defects allows definite carrier and prenatal diagnosis in virtually every family with haemophilia B. We report a study of the family of an isolated patient. Analysis of all the essential regions of the patient's factor IX gene (promoter, exons, transcript processing signals) revealed two mutations: one C----T transition at residue 17762 and another at residue 30890. The former created a translation stop at codon 116, and the latter caused substitution of His 257 by Tyr. The translation stop is an obvious detrimental mutation, while the His 257----Tyr substitution has uncertain functional consequences. From analysis of other family members, it was found that the first mutation had occurred at grandpaternal... (More)

Rapid identification of gene defects allows definite carrier and prenatal diagnosis in virtually every family with haemophilia B. We report a study of the family of an isolated patient. Analysis of all the essential regions of the patient's factor IX gene (promoter, exons, transcript processing signals) revealed two mutations: one C----T transition at residue 17762 and another at residue 30890. The former created a translation stop at codon 116, and the latter caused substitution of His 257 by Tyr. The translation stop is an obvious detrimental mutation, while the His 257----Tyr substitution has uncertain functional consequences. From analysis of other family members, it was found that the first mutation had occurred at grandpaternal gametogenesis, in keeping with the negative family history, while the second was of more remote origin and did not reduce the maternal grandfather's factor IX coagulant and antigen level. This neutral mutation (His 257----Tyr) pinpoints a poorly conserved amino acid in factor IX and related serine proteases. Its coexistence with a detrimental mutation stresses the need to examine all essential regions of a gene before attempting to interpret the functional consequences of its sequence changes.

(Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Antigens, Base Sequence, Child, Preschool, Codon, Exons, Factor IX, Hemophilia B, Heterozygote Detection, Humans, Male, Molecular Sequence Data, Mutation, Nucleic Acid Amplification Techniques, Pedigree, Polymerase Chain Reaction, Case Reports, Journal Article, Research Support, Non-U.S. Gov't
in
Human Genetics
volume
85
issue
2
pages
4 - 200
publisher
Springer
external identifiers
  • Scopus:0025297773
ISSN
0340-6717
DOI
10.1007/BF00193196
language
English
LU publication?
yes
id
012acce9-466a-41c2-b625-52fc1540a556
date added to LUP
2016-11-08 15:01:26
date last changed
2016-11-21 09:33:34
@misc{012acce9-466a-41c2-b625-52fc1540a556,
  abstract     = {<p>Rapid identification of gene defects allows definite carrier and prenatal diagnosis in virtually every family with haemophilia B. We report a study of the family of an isolated patient. Analysis of all the essential regions of the patient's factor IX gene (promoter, exons, transcript processing signals) revealed two mutations: one C----T transition at residue 17762 and another at residue 30890. The former created a translation stop at codon 116, and the latter caused substitution of His 257 by Tyr. The translation stop is an obvious detrimental mutation, while the His 257----Tyr substitution has uncertain functional consequences. From analysis of other family members, it was found that the first mutation had occurred at grandpaternal gametogenesis, in keeping with the negative family history, while the second was of more remote origin and did not reduce the maternal grandfather's factor IX coagulant and antigen level. This neutral mutation (His 257----Tyr) pinpoints a poorly conserved amino acid in factor IX and related serine proteases. Its coexistence with a detrimental mutation stresses the need to examine all essential regions of a gene before attempting to interpret the functional consequences of its sequence changes.</p>},
  author       = {Montandon, A J and Green, P M and Bentley, D R and Ljung, R and Nilsson, Inga Marie and Giannelli, F},
  issn         = {0340-6717},
  keyword      = {Antigens,Base Sequence,Child, Preschool,Codon,Exons,Factor IX,Hemophilia B,Heterozygote Detection,Humans,Male,Molecular Sequence Data,Mutation,Nucleic Acid Amplification Techniques,Pedigree,Polymerase Chain Reaction,Case Reports,Journal Article,Research Support, Non-U.S. Gov't},
  language     = {eng},
  number       = {2},
  pages        = {4--200},
  publisher    = {ARRAY(0xb7c9a30)},
  series       = {Human Genetics},
  title        = {Two factor IX mutations in the family of an isolated haemophilia B patient : direct carrier diagnosis by amplification mismatch detection (AMD)},
  url          = {http://dx.doi.org/10.1007/BF00193196},
  volume       = {85},
  year         = {1990},
}