guidebook. - Fanconi Anemia Research Fund

Chapter 2: Diagnostic Evaluation of FA
45
ESCO2 sequencing for Nijmegen breakage and Roberts
syndromes. 12 Mutation testing is used to confirm known
cases and for family studies to determine affected or
carrier status. Genetic counseling should be included in
these processes, because of the complicated explanations
and support needed for the families.
Importance of Gene and Mutation
Information
Current
The majority of patients worldwide are in the FANCA
group, in which several hundred mutations have been
documented. However, there are several populations
in which there is a founder effect, leading to a
limited number of specific mutations that can be targeted
for genetic diagnoses. These include Ashkenazi
Jewish FANCC IVS4+4 A>T or FANCD1/BRCA2
6174delT; non-Ashkenazi Jewish Moroccan FANCA
2172-2173insG or FANCA 4275delT; Tunisian FANCA
890-893del; Indian FANCA 2574C>G (S858R); Israeli
Arabs FANCA del ex 6-31, FANCA IVS 42-2A>C,
and FANCG IVS4+3A>G; Japanese FANCC IVS4+4
A>T; Afrikaner FANCA del ex 12-31 and FANCA del
ex 11-17; Brazil FANCA 3788-3790del; Spanish Gypsy
FANCA 295C>T; and Sub-Saharan African Black
FANCG 637-643delTACCGCC. Patients from those
specific groups can be tested initially for those mutations,
and premarital and prenatal testing are possible.
In families in which the proband’s mutation is known,
mutation testing of family members permits accurate
diagnosis of homozygotes and heterozygotes, leading to
appropriate medical management and focused genetic
counseling. Premarital screening, prenatal diagnosis,
and preimplantation genetic diagnosis can be performed.
Potential bone marrow transplant donors, such