Authors:
M Upadhyaya, M Ruggieri, J Maynard, M Osborn, C Hartog, S Mudd, M Penttinen, I Cordeiro, M Ponder, BA Ponder, M Krawczak, DN Cooper
Journal name: 
Hum Genet
Citation info: 
102(5):591-597
Abstract: 
Mutation screening in neurofibromatosis type 1 (NF1) families has long been hampered by the complexity of the NF1 gene. By using a novel multi-track screening strategy, 67 NF1 families (54 two-generation, 13 three-generation) with a de novo mutation in the germline of the first generation were studied with two extragenic and 11 intragenic markers. The pathological lesion was identified in 31 cases. Loss of heterozygosity (LOH) in the affected individual revealed a gross gene deletion in 15 of the two-generation families; in 12 (80%) of them, the deletion was maternally derived. Eleven patients with a gross deletion exhibited developmental delay, ten had dysmorphic features and six manifested a learning disability. No gross deletion was apparent in any of the 13 three-generation families, suggesting that such lesions are subject to more intense selection. In these families, the new mutation was of paternal origin in 11 kindreds and the underlying mutational event could be characterised in three of them.
DOI: 
http://doi.org/10.1007/s004390050746
Research group: 
Ponder Group
E-pub date: 
01 May 1998
Users with this publication listed: 
Bruce Ponder