2007 Mutations in patients with factor XIII deficiency

Mutations in patients with factor XIII deficiency

Gene	Mutation	Location	Domain	Type	Genotype	Origin	Activity U/dL	Antigen U/dL	Expression	Comments	Reference
XIII-A	nt -7 del 20 bp and Ala394Val IVS4+2 ins T ( Nagoya 1)	UTR Exon 9 IVS4	Core	Splicing Missense Splicing	Comp het	Japan	<5	<5			1, 2
XIII-A	nt 27 del T*	Exon 2	Activation peptide	Frameshift	Hom	Sweden	<3	<5		Also found in heterozygote from Denmark	3
XIII-A	nt 131 del AG	Exon 3	Activation	Frameshift	Hom	Japan	<3	<5			4
XIII-A	Asn60Lys Tyr441stop	Exon 3 Exon 11	b sandwich Core	Missense Nonsense	Comp het	Caucasian	<1	<5	Yes		5, 6, 7
XIII-A	Tyr69stop	Exon 3	b sandwich	Nonsense	Hom	India					8
XIII-A	Arg77His*	Exon 3	b sandwich	Missense	Hom	Iran	<3	0			9
XIII-A	Arg77His*	Exon 3	b sandwich	Missense	Hom	Switzerland	2.9	0.9	Yes	First family described in 1960	10
XIII-A	Arg77His* nt 607 del G	Exon 3 Exon 5	b sandwich Core	Missense Splicing	Comp het	Switzerland	5.4	1.8		Measured under replacement therapy	10 #
XIII-A	Arg78Cys IVS5-1 G>C	Exon 3 Intron 5	b sandwich	Missense Splicing	Comp het						11
XIII-A	nt 249 del 13	Exon 3	b sandwich	Frameshift	Hom	Greece	<5				12
XIII-A	nt 291 del GG and nt 303 ins 6 bp IVS3+5 G>A	Exon 3 Intron 3	b sandwich	Frameshift Splicing	Comp het						7
XIII- A	nt 319 G>T*	Exon 3	b sandwich	Splicing	Hom						7
XIII- A	nt 319 G>T* Undefined	Exon 3	b sandwich	Splicing	Comp het	U.K					13
XIII-A	IVS3+6 T>C Arg661stop *	Intron 3 Exon 14	Barrel 2	Splicing Nonsense	Comp het	Finland	<1				14, 15
XIII-A	IVS3-1 G>T	Intron 3		Splicing	Hom	UK	<1				7
XIII-A	nt 398 ins G Ser413Leu*	Exon 4 Exon 10	b sandwich Core	Frameshift Missense	Comp het		<2				16
XIII-A	Met159Arg*	Exon 4	b sandwich	Missense	Hom	Switzerland	1.3	<0.5	Yes		10 #
XIII-A	Met159Arg* Arg661stop*	Exon 4 Exon 14	b sandwich Barrel 2	Missense Nonsense	Comp het	Switzerland	1.8	<0.5			10 #
XIII-A	Arg171stop Undefined ( Bristol)	Exon 4	b sandwich	Nonsense	Comp het		<5				17
XIII-A	Gly210Arg	Exon 5	Core	Missense	Hom	India	9	10	Yes	Measured under replacement therapy	18, 19
XIII-A	Gly215Arg IVS10+1 G>A	Exon 5 Intron 10	Core Core	Missense Splicing	Comp het	Serbia	5.7	2.2	Yes	Measured under replacement therapy	10 #
XIII-A	nt 689 del A	Exon 5	Core	Frameshift	Hom	Iran	18	16		Measured under replacement therapy	9
XIII-A	IVS5-1 G>A* Asn541Lys*	Intron 5 Exon 12	Barrel 1	Splicing Missense	Comp het	U.K		<5			20
XIII-A	IVS5-1 G>A*	Intron 5		Splicing	Hom	Netherlands	<5	<5			21
XIII-A	IVS5-1 G>A*	Intron 5		Splicing	Hom	Czechoslovakia	0.5	0.1		Also found in homozygotes from Kosovo and Macedonia	10 #
XIII-A	Leu235Arg	Exon 6	Core	Missense	Hom			<5			22
XIII- A	nt 709 del G Trp691stop	Exon 6 Exon 15	Core Barrel 2	Frameshift Nonsense	Comp het	U.K					13
XIII-A	Met242Thr Arg661stop*	Exon 6 Exon 14	Core Barrel 2	Missense Nonsense	Comp het	Finland					15, 23
XIII-A	Arg252Ile Arg326Gln*	Ex 6 Ex 8	Core Core	Missense Missense	Comp het	Germany	<2	<1	Yes		3, 23
XIII-A	Arg260Cys* Undefined ( Nagoya 2)	Exon 6	Core	Missense	Comp het	Japan	<5				24
XIII-A	Arg260Cys* Trp375Cys	Exon 6 Exon 9	Core Core	Missense Missense	Comp het	Switzerland	8.4	11.9	Yes	Measured under replacement therapy	10 #
XIII-A	Arg260Cys* His716Arg*	Exon 6 Exon 15	Core Barrel 2	Missense Missense	Comp het	Switzerland	5.9	2.2	Yes	Measured under replacement therapy	10 #
XIII-A	Arg260Cys*	Exon 6	Core	Missense	Hom	Iran	8	3		Measured under replacement therapy	9
XIII-A	Arg260His*	Exon 6	Core	Missense	Hom	Syria			Yes		25
XIII-A	Arg260His*	Exon 6	Core	Missense	Hom	India					8
XIII-A	Arg260His*	Exon 6	Core	Missense	Hom	Iran	<3	<1			9
XIII-A	Arg260Leu	Exon 6	Core	Missense	Hom	Israeli Arab	4	<5	Yes	Measured under replacement therapy	18, 19
XIII- A	Gly262Glu Val316Phe*	Exon 6 Exon 7	Core Core	Missense Missense	Comp het	Dutch	<1	<12.5			26
XIII-A	Ser263Phe IVS14-1 G>A	Exon 6 Intron 14	Core	Missense Splicing	Comp het	India					8
XIII-A	Tyr283Cys Undefined	Exon 7	Core	Missense	Comp het	Italy	<2	<5	Yes		27, 28
XIII A	nt 869 ins C	Exon 7	Core	Frameshift	Hom	Tunis	4				18
XIII A	nt 874 ins G	Exon 7	Core	Frameshift	Hom	India					8
XIII-A	Ser295Arg*	Ex on 7	Core	Missense	Hom	Pakistan					13, 29
XIII-A	Val316Phe* Arg326Gln*	Exon 7 Exon 8	Core Core	Missense Missense	Comp het	Netherlands	<1				30
XIII A	Ala318Val nt 1652 del 10 bp	Exon 7 Exon 12	Core Barrel 1	Missense Frameshift	Comp het	Athiopian Jewish	2	2	Yes		18, 19
XIII-A	IVS7+1 G>A and exon 8 last nt T>G	Intron 7 Exon 8	Core	Splicing	Hom		<1				31
XIII-A	Arg326Gln*	Exon 8	Core	Missense	Hom	Germany	<2	<1	Yes		3, 23
XIII-A	Arg326Gln*	Exon 8	Core	Missense	Hom	Pakistan					32
XIII-A	Arg326Gln* Undefined	Exon 8	Core	Missense	Comp het	Netherlands	<1				30
XIII-A	Arg326stop	Exon 8	Core	Nonsense	Hom	Pakistan					13
XIII-A	nt 1033 del AAT	Exon 8	Core	Del Asn 344	Hom	Thailand	5		Yes		33
XIII-A	Leu354Pro*	Exon 8	Core	Missense	Hom	Pakistan	<5			Additional homozygote from India	18, 34
XIII-A	Arg382Ser	Exon 9	Core	Missense	Hom	Iran	6	5		Measured under replacement therapy	9
XIII-A	Thr398Asn	Exon 9	Core	Missense	Hom	India	1.6	1.3	Yes		18, 19
XIII-A	Gln400stop	Exon 9	Core	Nonsense	Hom	Turkey	<1				35
XIII-A	nt 1202 ins C*	Exon 9	Core	Frameshift	Hom	Turkey				Additional homozygote from Greece	36, 37
XIII-A	Arg408Gln Big del exons 4-11	Exon 10 Exon 4-11	Core	Missense Big deletion	Comp het	UK	<1	<1			7, 38
XIII-A	Ser413Leu*	Exon 10	Core	Missense	Hom	India					8
XIII-A	Val414Phe*	Exon 10	Core	Missense	Hom	Malaysia-India	6	6		Measured under replacement therapy	39
XIII-A	Val414Phe*	Exon 10	Core	Missense	Hom	India			Yes		8, 35
XIII-A	Gly420Ser	Exon 10	Core	Missense	Hom	Thailand					40
XIII-A	nt 1392 del AATT* Undefined	Exon 11	Core	Frameshift	Comp het	France	<1				35
XIII-A	nt 1392 del AATT*	Exon 11	Core	Frameshift	Hom						41
XIII-A	nt 1405 del CAAA	Exon 11	Core	Frameshift	Hom	Turkey					36
XIII A	IVS11+1 G>T	Intron 11		Splicing	Hom	Indian Jewish	2.5	5		Measured under replacement therapy	18
XIII-A	Leu498Pro Arg661stop*	Exon 12 Exon 14	Core Barrel 2	Missense Nonsense	Comp het	Sweden	<2	<1	Yes		3, 23
XIII-A	Gly501Arg	Exon 12	Core	Missense	Het				Yes		5, 6
XIII-A	Asn541Lys	Exon 12	Barrel 1	Missense	Hom	Turkey					36
XIII-A	nt1643 ins A	Exon 12	Barrel 1	Splicing	Hom	India					8
XIII-A	Gly562Arg	Exon 12	Barrel 1	Missense					Yes		41
XIII-A	Leu660Pro*	Exon 14	Barrel 2	Missense	Hom	Israeli Arabs	<1	<5		Founder effect, Carriership of 0.67% in Israeli Arabs	42
XIII-A	Arg661stop*	Exon 14	Barrel 2	Nonsense	Hom	Finland	<1		Yes		3, 15, 23
XIII-A	Arg661stop*	Exon 14	Barrel 2	Nonsense	Hom	India	6	2			18
XIII-A	Leu667Pro (Calgary)	Exon 14	Barrel 2	Missense	Hom	Canada	1	<6			43
XIII-A	nt 2035 del AAG	Exon 14	Barrel 2	Del Lys 678	Hom		<2	<5			22
XIII-A	nt 2045 G>A*	Exon 14	Barrel 2	Splicing	Hom	UK	<1			Published as Arg681His	7, 44
XIII-A	nt 2045 G>A*	Exon 14	Barrel 2	Splicing	Hom	Pakistan				Founder effect Additional homozygotes from India.	18, 32
XIII-A	nt 2067 del C	Exon 15	Barrel 2	Frameshift	Hom	Iran	<3	<1			9
XIII- A	Arg703Trp His716Arg*	Exon 15 Exon 15	Barrel 2 Barrel 2	Missense Missense	Comp het	China	<5	<1			45

XIII B	IVS1-2 del A*	Intron 1		Splicing	Hom	Japan		<10		Founder effect	46
XIII B	IVS1-2 del A* Cys430Phe	Intron 1 Exon 8	Sushi 7	Splicing Missense	Comp het	Japan		<5	Yes		47, 48, 49
XIII B	IVS1-2 del A* nt 1498 del G	Intron 1 Exon 9	Sushi 8	Splicing Frameshift	Comp het	Japan		<10	Yes		46
XIII B	nt 299 ins A AC*	Exon 3	Sushi 2	Frameshift	Hom	Italy		<5		Founder effect	50, 51

Nucleotide numbers of FXIII-A subunit are based on the Genebank file NM_000129 using the A (nucleotide 102) of the ATG initiator methionine as +1.
Nucleotide numbers of FXIII B subunit are based on the Genebank file NM_001994 using the A (nucleotide 36) of the ATG initiator methionine as +1.
Amino acid numbers of FXIII-A subunit are based on the initiator methionine as O and its succeeding serine as +1 (this is due to wrong numbering cited in most papers.)
* A Mutation that was identified in more than 1 family.
# Matching the genotypes to phenotypes is unavailable in the paper but was kindly communicated by the authors.

References

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