Of 7,028 disorders with suspected Mendelian inheritance, 1,139 are recessive and have an established molecular basis. Although individually uncommon, Mendelian diseases collectively account for ~20% of infant mortality and ~18% of pediatric hospitalizations. Molecular diagnostic testing is currently available for only ~300 recessive disorders. Preconception screening, together with genetic counseling of carriers, has resulted in remarkable declines in the incidence of several severe recessive diseases including Tay-Sachs disease and cystic fibrosis. However, extension of preconception screening and molecular diagnostic testing to most recessive disease genes has hitherto been impractical. Recently, we reported a preconception carrier screen / molecular diagnostic test for 448 recessive childhood diseases. The current status of this test is reviewed here. Currently, this reports analytical validity of the comprehensive carrier test. As the clinical validity and clinical utility in the contexts described is ascertained, this article will be updated.
Affiliation: Children's Mercy Hospitals and Clinics, Kansas City, MO
Stephen F. Kingsmore joined Children's Mercy Hospital and Clinics, Kansas City, MO, in 2011 to set up pediatric genomic medicine (a structured approach to disease diagnosis & management that prominently features genome sequence information). Previously, Dr. Kingsmore was President of the National Center for Genome Resources, Santa Fe, NM, Chief Operating Officer of Molecular Staging Inc., Vice President of Research of CuraGen Corp. and Assistant Professor at the Univ. Florida. Dr. Kingsmore received a B.Sc., M.B., Ch.B., B.A.O. and D.Sc. from Queen's University Belfast, N. Ireland. He completed residency in Internal Medicine and fellowship in Rheumatology at Duke. He is a Fellow of the Royal College of Pathologists (UK). He has published over one hundred research papers and identified seven disease genes.