Anemia

Research Article

Diagnosis of Fanconi Anemia: Mutation Analysis by Multiplex Ligation-Dependent Probe Amplification and PCR-Based Sanger Sequencing

Table 3

Mutations detected in a cohort of 54 patients by screening FANCA, FANCC, FANCE, FANCF and FANCG.


			Allele 1			Allele 2
	Country of origin¹	Gene	DNA change	Effect	Number of database entries	DNA change	Effect	Number of database entries

1	ES	FANCA	ex16_17del	del	12x	c.1115_1118del	p.Val372fs	62x
2	PT	FANCA	c.718C>T	p.Gln240X	2x	c.2870G>A	W957X	1x
3	NL	FANCA	ex15del	del	3x	ex15del	del	3x
4	NL	FANCA	c.3788_3790del	p.Phe1263del	215x	c.3788_3790del	p.Phe1263del	215x
5	CA	FANCA	c.718C>T	pGlnx240X	2x	c.1085T>C	p.Leu362Pro	novel
6	PT	FANCA	c.3788_3790del	p.Phe1263del	215x	c.4130C>G	p.Ser1377X	1x
7	IE	FANCA	c.2812_2830dup	p.Asp944fs	3x	c.2812_2830dup	p.Asp944fs	3x
8	AU	FANCA	c.2303T>C	p.Leu768Pro	5x	c.2303T>C	p.Leu768Pro	5x
9	NL	FANCA	c.862G>T	p.Glu288X	1x	c.862G>T	p.Glu288X	1x
10	NL	FANCA	ex11_33del	del	1x	c.2121delC	p.Asn707fs	novel
11	DK	FANCA	ex1_8del	del	1x	c.3788_3790del	p.Phe1263del	215x
12	UK	FANCA	c.337_338del	p.Ala114fs	1x	c.3349A>G	p.Arg1117Gly	2x
13	UK	FANCA	c.3568C>T	p.Gln1190X	novel	c.3568C>T	p.Gln1190X	novel
14	NL	FANCA	c.487delC	p.Arg163fs	1x	c.2851C>T	p.Arg951Trp	11x
15	SE	FANCA	c.88delG	p.Val30fs	novel	c.100A>T	p.Lys34X	2x
16	NL	FANCA	c.862G>T	p.Glu288X	9x	c.1771C>T	p.Arg591X	9x
17	PT	FANCA	c.1709_1715+4del	p.Glu570fs	novel	c.3430C>T	p.Arg1144Trp	novel
18	NO	FANCA	c.100A>T	p.Lys34X	2x	c.1378C>T	p.Arg460X	novel
19	PT	FANCA	ex15_17del	del	2x	ex15_17del	del	2x
20	NL	FANCA	c.2982-192A>G	splice²	novel	ex7_31del	del
21	AU	FANCA	c.427-8_427-5del	splice	novel	c.1771C>T	p.Arg591X	9x
22	AU	FANCA	c.3491C>T	p.Pro1164Leu	novel	c.3491C>T	p.Pro1164Leu	novel
23	CA	FANCA	ex4_29del	del	novel	ex31del	del	6x
24	NL	FANCA	c.3391A>G	p.Thr1131Ala	15x	c.3391A>G	p.Thr1131Ala	15x
25	GR	FANCA	c.2T>C	p.Met1?	1x	c.3788_3790del	p.Phe1263del	215x
26	IE	FANCA	c.851dup	p.Val285fs	novel	c.2534T>C	p.Leu845Pro	4x
27	NL	FANCA	c.2852G>A	p.Arg951Gln	6x	c.3624C>T	p.= (splice)	2x
28	AU	FANCA	c.331_334dup	p.Leu112fs	novel	ex22_29del	del	novel
29	NL	FANCA	c.862G>T	p.Glu288X	9x	c.3920delA	p.Gln1307fs	2x
30	IR	FANCA	ex21del	del	novel	ex21del	del	novel
31	SE	FANCA	ex1_12del	del	novel	ex22_29del	del	novel
32	NL	FANCB	c.755_767del	p.Leu252fs	novel	—	—	—
33	NL	FANCC	c.67delG	p.Asp23fs	50x	c.553C>T	p.Arg185X	14x
34	NL	FANCC	c.67delG	p.Asp23fs	50x	c.67delG	p.Asp23fs	50x
35	CA	FANCC	c.67delG	p.Asp23fs	50x	c.553C>T	p.Arg185X	14x
36	NL	FANCC	c.67delG	p.Asp23fs	50x	c.1155-1G>C	splice	novel
37	NL	FANCC	c.67delG	p.Asp23fs	50x	c.67delG	p.Asp23fs	50x
38	NL	FANCC	c.67delG	p.Asp23fs	50x	c.467delC	p.Ser156fs	novel
39	PT	FANCE	c.1111C>T	p.Arg371Trp	6x	c.1111C>T	p.Arg371Trp	6x
40	UK	FANCF	c.496C>T	p.Gln166X	4x	c.496C>T	p.Gln166X	4x
41	UK	FANCG	c.307+2delT	splice	novel	c.307+2delT	splice	novel
42	UK	FANCG	c.1471_1473delinsG	p.Lys491fs	novel	c.1471_1473delinsG	p.Lys491fs	novel
43	NL	FANCG	c.65G>C	p.Arg22Pro	6x	c.65G>C;	p.Arg22Pro	6x
44	IR	FANCG	c.307+1G>C	splice	21x	c.307+1G>C	splice	21x
45	NL	FANCG	c.85-1G>A	splice	novel	c.85-1G>A	splice	novel

¹Country of origins: AU: Australia; CA: Canada; DK: Denmark; ES: Spain; GR: Greece; IE: Ireland; IR: Iran; NL: Netherlands; PT: Portugal; SE: Sweden; UK: United Kingdom
Number of database entries refers to the FA database at: http://www.rockefeller.edu/fanconi/.
The pathogenic state of novel missense mutations is based upon in silico prediction algorithms (SIFT, POLYPHEN2, Align GVGD), the presence of a second clearly pathogenic mutation in the same gene and segregation in the family.
²Effect c.2982-192A>G: by studying cDNA it was shown that the mutation created a new splice donor site resulting in an aberrant mRNA.