RGD Reference Report - Identification of eight novel coagulation factor XIII subunit A mutations: implied consequences for structure and function. - Rat Genome Database

RGD Reference Report - Identification of eight novel coagulation factor XIII subunit A mutations: implied consequences for structure and function. - Rat Genome Database

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Identification of eight novel coagulation factor XIII subunit A mutations: implied consequences for structure and function.
Authors:	Ivaskevicius, V Biswas, A Bevans, C Schroeder, V Kohler, HP Rott, H Halimeh, S Petrides, PE Lenk, H Krause, M Miterski, B Harbrecht, U Oldenburg, J
Citation:	Ivaskevicius V, etal., Haematologica. 2010 Jun;95(6):956-62. doi: 10.3324/haematol.2009.017210. Epub 2010 Feb 23.
RGD ID:	10450729
Pubmed:	PMID:20179087 (View Abstract at PubMed)
PMCID:	PMC2878794 (View Article at PubMed Central)
DOI:	DOI:10.3324/haematol.2009.017210 (Journal Full-text)
BACKGROUND: Severe hereditary coagulation factor XIII deficiency is a rare homozygous bleeding disorder affecting one person in every two million individuals. In contrast, heterozygous factor XIII deficiency is more common, but usually not associated with severe hemorrhage such as intracranial bleeding or hemarthrosis. In most cases, the disease is caused by F13A gene mutations. Causative mutations associated with the F13B gene are rarer. DESIGN AND METHODS: We analyzed ten index patients and three relatives for factor XIII activity using a photometric assay and sequenced their F13A and F13B genes. Additionally, structural analysis of the wild-type protein structure from a previously reported X-ray crystallographic model identified potential structural and functional effects of the missense mutations. RESULTS: All individuals except one were heterozygous for factor XIIIA mutations (average factor XIII activity 51%), while the remaining homozygous individual was found to have severe factor XIII deficiency (<5% of normal factor XIII activity). Eight of the 12 heterozygous patients exhibited a bleeding tendency upon provocation. CONCLUSIONS: The identified missense (Pro289Arg, Arg611His, Asp668Gly) and nonsense (Gly390X, Trp664X) mutations are causative for factor XIII deficiency. A Gly592Ser variant identified in three unrelated index patients, as well as in 200 healthy controls (minor allele frequency 0.005), and two further Tyr167Cys and Arg540Gln variants, represent possible candidates for rare F13A gene polymorphisms since they apparently do not have a significant influence on the structure of the factor XIIIA protein. Future in vitro expression studies of the factor XIII mutations are required to confirm their pathological mechanisms.

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
F13A1	Human	factor XIII deficiency		IAGP		DNA:nonsense mutations and missense mutations:cds:	RGD
F13a1	Rat	factor XIII deficiency		ISO	F13A1 (Homo sapiens)	DNA:nonsense mutations and missense mutations:cds:	RGD
F13a1	Mouse	factor XIII deficiency		ISO	F13A1 (Homo sapiens)	DNA:nonsense mutations and missense mutations:cds:	RGD

Genes (Rattus norvegicus)


F13a1 (coagulation factor XIII A1 chain)

Genes (Mus musculus)


F13a1 (coagulation factor XIII, A1 subunit)

Genes (Homo sapiens)


F13A1 (coagulation factor XIII A chain)