Genomic Organisation of the PPP1CC gene located within the Noonan syndrome critical interval. A.H. Crosby1, M. Salehpour1, R. Dong1, K. Kalidas1, A. Ion1, S. Jeffery1, M. Patton1, H. Kremer2, M. van Reen2, I. van der Burgt2, H. Brunner2, E. Mariman2, R. Kucherlapati3, K. Montgomery3. 1) Dept Medical Genetics, St George Hosp Med Sch, London, England; 2) Dept Human Genetics, University Hosp Nijmegen, Nijmegen, The Netherlands; 3) Dept Molecular Genetics, Albert Einstein College Medicine, NY, USA.
Noonan syndrome (NS) is an autosomal dominant developmental disorder characterised by typical facial dysmorphology, congenital heart defects and short stature. Whilst we have shown that this condition is genetically heterogeneous, we have previously localised one gene for NS to a 5cM interval on the long arm of chromosome 12 at band 12q24.1. More recent work has involved the fine mapping and characterisation of a number of both novel and previously described transcripts within the interval. One of these transcripts, the PPP1CC gene, is a serine-threonine protein phosphatase. Due to their involvement in a variety of cellular functions from muscle contraction through to cell cycle progression, the protein phosphatases constitute potential candidates for NS. In order to examine this gene for mutations, we have determined its genomic organisation. PPP1CC comprises 7 exons which span approximately 17.5kb of genomic DNA. This gene is now being evaluated for disease-specific mutations in our large cohort of NS patients.