Current Projects

The research activities of the members of the Department of Medical Genetics include a variety of topics:

Neurofibromatosis Type 1 (NF1)

  • A multicenter clinical treatment trial with Pirfenidone—this study is open for accrual.
  • A Phase II clinical treatment trial with AZD217 for adults with NF1: Mayo is the coordinating center for this seven center study that is now open for accrual. Mayo also has a Neurofibromatosis Clinic.

Schwannoma research

  • Effects of hormone therapy on human schwannoma xenoimplants in SCID mice.
  • Subdural vestibular schwannoma xenografts in SCID mice in collaboration with Mayo Otolaryngology Department.

Breast-ovarian cancer research

  • Inherited Breast Cancer Study -involves segregation analysis, sequence conservation and functional studies to attempt to reclassify BRCA1 and BRCA2 variants of uncertain significance as either deleterious mutations or benign polymorphisms.
  • Family Breast & Ovarian Cancer Study involves the utilization of genetic epidemiology to attempt to provide more information to BRCA positive families and to enroll high risk BRCA negative families for further gene discovery and genomic rearrangement analysis.
  • Evaluation of multiple BRCA gene probability prediction models.

Spontaneous arterial dissections

  • This study is enrolling individuals age 50 or younger in whom no current genetic explanation is apparent, in order to search for other genes that may predispose to this condition.

Gene therapy studies for Very Long Chain Acyl Co-A Dehydrogenase (VLCAD) deficiency (a disorder of fatty acid beta oxidation)

  • This study is working toward a liver gene delivery system that would be able to safely and stably correct VLCAD deficiency, using an Adeno-associated virus vectors to deliver VLCAD expression cassettes to the liver following IV administration. In addition, collaboration is underway with researchers at the University of MN to develop a plasmid based delivery system in conjunction with in vivo selection for corrected hepatocytes as an alternative method.

Familial melanoma

  • Families with a very strong history of melanoma are being studied in collaboration with the Melanoma Linkage Consortium for further understanding of underlying gene(s) that may account for this type of aggregation.

Colon Cancer Family Registry

  • Mayo is a member of this multinational consortium dedicated to furthering knowledge of the environmental and genetic predisposing factors in colorectal cancer. Further information on this extensive project can be found at http://epi.grants.cancer.gov/CFR/about_colon.html. High risk families are currently being enrolled.

Familial Cancer Program

  • The Department of Medical Genetics has a longstanding interest in identification and management of all types of familial aggregation of cancers. Currently over 50 specific rare genetic syndromes have been defined that warrant individualized cancer risk management. Clinical consultation for genetic risk assessment may lead to enrollment in this program. An update of The Concise Handbook of Family Cancer Syndromes (Journal of the National Cancer Institute. 90(14):1039-71, 1998 is in preparation now).

Rare or suspected genetic disorders

  • The Department has a long history of promoting knowledge regarding rare or novel genetic disorders and sees this as a very important function for those families for which information is so limited.

Lysosomal storage disease

  • A multidisciplinary group is being developed to conduct research and to provide diagnostic and therapeutic services for people of all ages with lysosomal storage diseases (LSDs). Although individually rare, these inherited diseases collectively affect thousands of people in the United sates and overseas. Effective therapies are being developed, but major gaps in understanding of basic mechanisms and natural history remain. Specific studies underway or planned at Mayo Clinic include:
    • A phase I/II trial of miglustat in adults and children with Niemann-Pick disease, type C. Mayo Clinic is partnering the Royal Manchester Children's Hospital in the United Kingdom in this study. The study is fully enrolled, and is currently in a maintenance phase.
    • In vitro studies of endosomal-lysosomal trafficking in LSDs, and the therapeutic effect of rab overexpression in the NPC mouse
    • Protocols under development include studies of the epidemiology of lysosomal storage diseases and newborn screening for LSDs

Congenital disorders of glycosylation

  • The congenital disorders of glycosylation (CDG) comprise a family of inherited diseases that most often present in childhood, with dysfunction of the nervous system, liver, heart, kidneys and immune system. Clinical researchers at Mayo Clinic are working with colleagues in laboratory genetics to refine and expand diagnostic techniques in addition to establishing a consortium to conduct natural history and therapeutic studies in patients affected by CDG