Single synonymous mutation in factor IX alters protein properties and underlies haemophilia B

Vijaya  L Simhadri; Nobuko Hamasaki-Katagiri; Brian  C Lin; Ryan Hunt; Sujata Jha; Sandra  C Tseng; Andrew Wu; Amber A A Bentley; Ran Zichel; Qi Lu; Lily Zhu; Darón  I Freedberg; Dougald  M Monroe; Zub E Sauna; Robert Peters; Anton A A Komar; Chava Kimchi-Sarfaty

Single synonymous mutation in factor IX alters protein properties and underlies haemophilia B

Vijaya L Simhadri
, Nobuko Hamasaki-Katagiri
, Brian C Lin
, Ryan Hunt
, Sujata Jha
, Sandra C Tseng
, Andrew Wu
, Amber A A Bentley
, Ran Zichel
, Qi Lu
, Lily Zhu
, Darón I Freedberg
, Dougald M Monroe
, Zub E Sauna
, Robert Peters
, Anton A A Komar
, Chava Kimchi-Sarfaty

Biological, Geological, and Environmental Sciences

Research output: Contribution to journal › Article

Abstract

Haemophilia B is caused by genetic aberrations in the F9 gene. The majority of these are non-synonymous mutations that alter the primary structure of blood coagulation factor IX (FIX). However, a synonymous mutation c.459G>A (Val107Val) was clinically reported to result in mild haemophilia B (FIX coagulant activity 15%-20% of normal). The F9 mRNA of these patients showed no skipping or retention of introns and/or change in mRNA levels, suggesting that mRNA integrity does not contribute to the origin of the disease in affected individuals. The aim of this study is to elucidate the molecular mechanisms that can explain disease manifestations in patients with this synonymous mutation.

Original language	English
Journal	Journal of medical genetics
State	Published - 2016

Cite this

@article{3e0c8890ac3e413cafd82125078dc004,

title = "Single synonymous mutation in factor IX alters protein properties and underlies haemophilia B",

abstract = "Haemophilia B is caused by genetic aberrations in the F9 gene. The majority of these are non-synonymous mutations that alter the primary structure of blood coagulation factor IX (FIX). However, a synonymous mutation c.459G>A (Val107Val) was clinically reported to result in mild haemophilia B (FIX coagulant activity 15\%-20\% of normal). The F9 mRNA of these patients showed no skipping or retention of introns and/or change in mRNA levels, suggesting that mRNA integrity does not contribute to the origin of the disease in affected individuals. The aim of this study is to elucidate the molecular mechanisms that can explain disease manifestations in patients with this synonymous mutation.",

author = "Simhadri, \{Vijaya L\} and Nobuko Hamasaki-Katagiri and Lin, \{Brian C\} and Ryan Hunt and Sujata Jha and Tseng, \{Sandra C\} and Andrew Wu and Bentley, \{Amber A A\} and Ran Zichel and Qi Lu and Lily Zhu and Freedberg, \{Dar{\'o}n I\} and Monroe, \{Dougald M\} and Sauna, \{Zub E\} and Robert Peters and Komar, \{Anton A A\} and Chava Kimchi-Sarfaty",

year = "2016",

language = "English",

journal = "Journal of medical genetics",

}

TY - JOUR

T1 - Single synonymous mutation in factor IX alters protein properties and underlies haemophilia B

AU - Simhadri, Vijaya L

AU - Hamasaki-Katagiri, Nobuko

AU - Lin, Brian C

AU - Hunt, Ryan

AU - Jha, Sujata

AU - Tseng, Sandra C

AU - Wu, Andrew

AU - Bentley, Amber A A

AU - Zichel, Ran

AU - Lu, Qi

AU - Zhu, Lily

AU - Freedberg, Darón I

AU - Monroe, Dougald M

AU - Sauna, Zub E

AU - Peters, Robert

AU - Komar, Anton A A

AU - Kimchi-Sarfaty, Chava

PY - 2016

Y1 - 2016

N2 - Haemophilia B is caused by genetic aberrations in the F9 gene. The majority of these are non-synonymous mutations that alter the primary structure of blood coagulation factor IX (FIX). However, a synonymous mutation c.459G>A (Val107Val) was clinically reported to result in mild haemophilia B (FIX coagulant activity 15%-20% of normal). The F9 mRNA of these patients showed no skipping or retention of introns and/or change in mRNA levels, suggesting that mRNA integrity does not contribute to the origin of the disease in affected individuals. The aim of this study is to elucidate the molecular mechanisms that can explain disease manifestations in patients with this synonymous mutation.

AB - Haemophilia B is caused by genetic aberrations in the F9 gene. The majority of these are non-synonymous mutations that alter the primary structure of blood coagulation factor IX (FIX). However, a synonymous mutation c.459G>A (Val107Val) was clinically reported to result in mild haemophilia B (FIX coagulant activity 15%-20% of normal). The F9 mRNA of these patients showed no skipping or retention of introns and/or change in mRNA levels, suggesting that mRNA integrity does not contribute to the origin of the disease in affected individuals. The aim of this study is to elucidate the molecular mechanisms that can explain disease manifestations in patients with this synonymous mutation.

M3 - Article

JO - Journal of medical genetics

JF - Journal of medical genetics

ER -