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Molecular basis of inherited factor XIII deficiency: identification of multiple mutations provides insights into protein function
Author(s) -
Anwar Rashida,
Stewart Alistair D.,
Miloszewski Krzysztof J. A.,
Losowsky Monty S.,
Markham Alexander F.
Publication year - 1995
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.1995.tb05376.x
Subject(s) - identification (biology) , genetics , function (biology) , computational biology , biology , mutation , gene , botany
Summary. Factor XIII (FXIII) is a zymogen essential for normal haemostasis. In inherited FXIII deficiency the majority of cases show absence of the FXHIa subunit. Molecular analysis of PCR‐amplified FXIIIa subunit exonic regions, and of RT‐PCR amplified cDNA from six patients with FXIIIa subunit deficiency, from five unrelated families, has revealed 10 sequence changes: three mutations resulting in abnormal splicing of pre‐mRNA, one nonsense mutation, one deletion/insertion change, three point mutations producing Val34Leu, Asn60Lys and Arg408Gln changes, and two silent mutations. In three families the patients are homozygous for a specific deficiency causing mutation, and patients from the remaining two families are compound heterozygotes. Understanding the molecular pathology of the disorder provides insights into the structure‐function relationships of the various domains within the FXm protein. From a clinical point of view, it enables direct diagnosis at the DNA level and may aid the development of FXIII analogues to promote wound healing.