Research Article A Dutch Fanconi Anemia FANCC Founder Mutation in Canadian Manitoba Mennonites
Yne de Vries,1 Nikki Lwiwski,2, 3 Marieke Levitus,1, 4 Bertus Kuyt,1 Sara J. Israels,2 Fr´ Arwert,1 Michel Zwaan,5, 6 Cheryl R. Greenberg,2 e 7 Hans Joenje,1 and Hanne Meijers-Heijboer1 Blanche P.Alter,
1 Department 2 Department
of Clinical Genetics, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands of Pediatrics and Child Health, University of Manitoba, 675 McDermot Avenue, Winnipeg MB, Canada R3E 0V9 3 Department of Cardiac Sciences, St. Boniface General Hospital, 405 Tache Avenue, Winnipeg MB, Canada R2H 2A6 4 Medical Diagnostic Center Amstelland, P.O.Box 8018, 1180 LA Amstelveen, The Netherlands 5 Department of Pediatrics, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands 6 Department of Pediatric Oncology/Hematology, Erasmus MC, Sophia Children’s Hospital, P.O. Box 2060, 3000 CB Rotterdam, The Netherlands 7 Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, Department of Health and HumanServices, National Cancer Institute, 6120 Executive Boulevard, 1Executive Plaza South, Room 7020, Rockville, MD 20852-7231, USA Correspondence should be addressed to Yne de Vries, firstname.lastname@example.org Received 9 January 2012; Accepted 22 March 2012 Academic Editor: Henri J. van de Vrugt Copyright © 2012 Yne de Vries et al. This is an open access article distributed under the Creative Commons AttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Fanconi anemia (FA) is a recessive DNA instability disorder associated with developmental abnormalities, bone marrow failure, and a predisposition to cancer. Based on their sensitivity to DNA cross-linking agents, FA cells have been assigned to 15 complementationgroups, and the associated genes have been identiﬁed. Founder mutations have been found in diﬀerent FA genes in several populations. The majority of Dutch FA patients belongs to complementation group FA-C. Here, we report 15 patients of Dutch ancestry and a large Canadian Manitoba Mennonite kindred carrying the FANCC c.67delG mutation. Genealogical investigation into the ancestors of the Dutchpatients shows that these ancestors lived in four distinct areas in The Netherlands. We also show that the Dutch and Manitoba Mennonite FANCC c.67delG patients share the same haplotype surrounding this mutation, indicating a common founder.
Fanconi anemia is an inherited chromosomal instability disorder associated with developmental abnormalities, bone marrow failure, and apredisposition to cancer. A characteristic feature of FA cells is their hypersensitivity to DNA crosslinking agents such as diepoxybutane (DEB) and mitomycin C (MMC). This feature has been used to assign FA cells to diﬀerent complementation groups. Currently, 15 diﬀerent complementation groups and their associated genes have been identiﬁed. Of these, 14 have an autosomal recessive, and one has an X-linked,mode of inheritance [1–3]. The majority of FA patients belong to complementation group
FA-A (65%) followed in frequency by FA-C (10%) and FA-G (10%) . The incidence of FA is approximately 1 in 130,000 live births, with a carrier frequency of approximately 1 in 181 . In some ethnic groups, however, the incidence is much higher due to genetic isolation and a founder eﬀect. For example,founder mutations in the FANCA gene have been found in several populations including the South African Afrikaners, Spanish Gypsies, and Moroccan Israeli Jews [6– 8]. Furthermore, sub-Saharan Blacks and Japanese carry founder mutations in the FANCG gene [9, 10]. In addition, FANCC c.456 + 4A > T (also known as IVS4 + 4A > T) is a previously identiﬁed founder mutation in the FANCC gene
2 in the...