HUM-MOLGEN DIAGnostics/Clinical Research

June, 10 1999
Cystic Fibrosis  mutation, D1152H

We are seeking collaborators to participate in a genotype-phenotype study of the CFTR exon 18 missense mutation, D1152H.  This mutation was first identified at the University of North Carolina at Chapel Hill and was presented as a Hot Science poster at the 1992 North American CF Conference (CFGAC Newsletter #49, Sept. 29, 1992). The index cases were three siblings notable for their extremely mild clinical presentations as well as their advanced age (60's to 70's).   Subsequently we have found this mutation among numerous normal-sweat patients with very mild lung disease of a variable nature and/or men with congenital bilateral absence of the vas deferens (CBAVD).  It's prominent role in CBAVD was described by poster presentations at last year's meeting in Montreal as well as at the 1998 American Society of Human Genetics meeting in Denver.
Additionally, recent work by Harry Cuppens has demonstrated reduced whole cell chloride currents when a D1152H-bearing CFTR cDNA vector is expressed in Xenopus oocytes.
Hardly any commercial laboratories screen for D1152H, and few, if any, academic institutions beyond UNC specifically test for this mutation. It is likely this limited scrutiny has prevented recognition of this mutation as having sufficient prevalence to warrant further research and, potentially, a higher clinical profile.
Interested laboratories who have already identified individuals with D1152H are requested to contact us for a clinical data submission form for each patient.  Labs who have not looked for D1152H but are interested in testing for it may contact us for a straightforward assay.  Once collaborators have been identified, control population information will be sought.


Dr. Kenneth Friedman, Ph.D., primary contact
919-966-0717 (FAX)

Lawrence M. Silverman, Ph.D.
Michael R. Knowles, M.D.
(Dep'ts of Pathology and Medicine, University of North Carolina at Chapel Hill, NC)
W. Edward Highsmith, Jr., Ph.D.
(Dep't of Pathology, University of Maryland, Baltimore, MD)