A Dutch Fanconi Anemia FANCC Founder Mutation in Canadian Manitoba Mennonites

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 complementation groups, 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 Dutch patients 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.

[1]  W. Marsden.  I and J , 2012 .

[2]  P. Rosenberg,et al.  How high are carrier frequencies of rare recessive syndromes? Contemporary estimates for Fanconi Anemia in the United States and Israel , 2011, American journal of medical genetics. Part A.

[3]  D. Schindler,et al.  SLX4, a coordinator of structure-specific endonucleases, is mutated in a new Fanconi anemia subtype , 2011, Nature Genetics.

[4]  Franca Fraternali,et al.  Mutation of the RAD51C gene in a Fanconi anemia–like disorder , 2010, Nature Genetics.

[5]  Hans Joenje,et al.  The genetic and molecular basis of Fanconi anemia. , 2009, Mutation research.

[6]  A. Innes,et al.  Unique disease heritage of the Dutch‐German Mennonite population , 2008, American journal of medical genetics. Part A.

[7]  H. Joenje,et al.  The Fanconi Anemia Pathway of Genomic Maintenance , 2006, Cellular oncology : the official journal of the International Society for Cellular Oncology.

[8]  C. Lewis,et al.  A common Fanconi anemia mutation in black populations of sub-Saharan Africa. , 2005, Blood.

[9]  C. Mathew,et al.  A common founder mutation in FANCA underlies the world highest prevalence of Fanconi anemia in Gypsy families from Spain , 2004 .

[10]  H. Joenje,et al.  Fanconi anaemia complementation groups in Germany and The Netherlands , 1996, Human Genetics.

[11]  M. Waterman,et al.  Canadian Mennonites and individuals residing in the Friesland region of the Netherlands share the same molecular basis of 17α-hydroxylase deficiency , 1992, Human Genetics.

[12]  V. Regitz-Zagrosek,et al.  The 2373insG mutation in the MYBPC3 gene is a founder mutation, which accounts for nearly one-fourth of the HCM cases in the Netherlands. , 2003, European heart journal.

[13]  T. Nakajima,et al.  Two common founder mutations of the fanconi anemia group g gene FANCG/XRCC9 in the Japanese population , 2003, Human mutation.

[14]  C. Mathew,et al.  Molecular and genealogical evidence for a founder effect in Fanconi anemia families of the Afrikaner population of South Africa , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[15]  R. Elhasid,et al.  Fanconi anaemia group A (FANCA) mutations in Israeli non‐Ashkenazi Jewish patients , 2000, British journal of haematology.

[16]  S. Asano,et al.  The IVS4 + 4 A to T mutation of the fanconi anemia gene FANCC is not associated with a severe phenotype in Japanese patients. , 2000, Blood.

[17]  H Niimura,et al.  Mutations in the gene for cardiac myosin-binding protein C and late-onset familial hypertrophic cardiomyopathy. , 1998, The New England journal of medicine.

[18]  G. T. te Meerman,et al.  Genomic sharing surrounding alleles identical by descent: Effects of genetic drift and population growth , 1997, Genetic epidemiology.

[19]  A. D’Andrea,et al.  Clinical variability of Fanconi anemia (type C) results from expression of an amino terminal truncated Fanconi anemia complementation group C polypeptide with partial activity. , 1996, Blood.

[20]  A. Auerbach,et al.  Carrier frequency of the IVS4 + 4 A-->T mutation of the Fanconi anemia gene FAC in the Ashkenazi Jewish population. , 1995, Blood.

[21]  C. Mathew,et al.  Mutation analysis of the Fanconi anemia gene FACC. , 1994, American journal of human genetics.

[22]  V. Doerksen.  Mennonite Historical Atlas , 1991 .