The Comprehensive Center for Fanconi Anemia & The Cytogenetic Facility

Preimplantation Genetic Diagnosis

To: The Fanconi Anemia Community
From: Alan D'Andrea M.D.
RE: FA gene mutation screening

Following the well-publicized story of Molly Nash and her family, we have had several inquiries regarding Fanconi Anemia gene mutational screening and preimplantation genetic diagnostics. We would like to share a few thoughts with the community.

First, our Fanconi Anemia Center at the Dana-Farber Cancer Institute and Children's Hospital in Boston has been providing subtyping information to FA families. Through our active collaboration with Markus Grompe and the OHSU, we have been able to provide subtyping information for greater than 60 FA families. Identification of your FA subtype (as subtype A-M) is now a relatively straightforward screen and is the first step toward precise mutational screening.

In contrast, identification of the precise mutation(s) carried by your family is a much more complex matter, and is generally a procedure which would take many months. The identification of mutations in the FA subtype A gene (the most common subtype) is very difficult, since the gene is so large. Also, once a putative mutation is identified, it must be confirmed by linkage analysis or by functional tests. So in short, even when we find a putative mutation in an FA gene in your family, we cannot be absolutely sure that this mutation is the cause of the disease in your family.

The exception is certain cases of FA subtype C. There is a well know mutation in the FA subtype C gene (IVS 4 + 4 A toT). This mutation is found primarily in patients with Ashkenazi Jewish ancestry. Because this mutation is relatively easy to screen and because this mutation is so clearly associated with the FA disease in these families, this mutation can be used in screening for carrier detection and for preimplantation diagnostics. So, at this time, only a few families would be eligible for preimplantation studies. Indeed, these would be families which carry a well-characterized FA gene mutation which is known to cause their disease.

Our laboratory and others are trying to improve methods of FA gene mutational screening. In the event that these methods are improved, we will alert the FA community and try to upscale our mutational screening for the families accordingly.