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

Table 2

Major recurrent mutations in FA.

Gene	Mutation*	Geographic/ethnic background	Comment	References
FANCA	c.3788_3790del (p.Phe1263del)	European, Brazilian	Relatively mild	[14, 15]
	c.1115_1118delTTGG (p.Val372fs)	European	Relatively mild	[16]
	Exon 12–17del; Exon 12–31del	South-African	Relatively common in Afrikaners	[17]
	c.295C>T (p.Gln99X)	Spanish Gypsy population	Worldwide highest prevalence of mutant FANCA allele	[18]
FANCC	c.711+4A>T (originally reported as IVS4+4A>T)	Homozygous in 80% of Ashkenazi Jewish FA; relatively common in Japan.	Severe phenotype in Jews, milder in Japanese.	[19–22]
	c.67delG (originally reported as 322delG)	Homozygous in approx. 50% of Dutch FA patients	Like other exon 1 mutations, relatively mild phenotype.	[19, 23–25]
FANCD2	c.1948-16T>G	Turkish	Founder mutation	[26]
FANCG	c.313G>T (p.Glu105X)	European	44% of mutated FANCG alleles in Germany.	[27]
	c.1077-2A>G	Portuguese/Brazilian	Founder mutation	[27, 28]
	c.1480+1G>C	French-Canadian	Founder mutation	[28]
	c.307+1G>C	Japanese	Founder mutation	[28, 29]
	c.1794_1803del (p.Trp599fs)	European		[28]
	c.637_643del (p.Tyr213fs)	Sub-Saharan Africa	82% of all black FA patients	[30]
FANCJ	c.2392C>T (p.Arg798X)		Found in ca. 50% of FA-J patients of diverse ancestry; ancient mutation or hot spot.	[11, 12]

Nucleotide numbering based on ATG = +1.
Published sequence variations in FA genes, with their descriptions conforming to the current nomenclature rules, are listed at http://www.rockefeller.edu/fanconi/.