RT Journal Article
SR Electronic
T1 Constitutional and mosaic large NF1 gene deletions in neurofibromatosis type 1.
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 468
OP 471
DO 10.1136/jmg.35.6.468
VO 35
IS 6
A1 S A Rasmussen
A1 S D Colman
A1 V T Ho
A1 C R Abernathy
A1 P H Arn
A1 L Weiss
A1 C Schwartz
A1 R A Saul
A1 M R Wallace
YR 1998
UL http://jmg.bmj.com/content/35/6/468.abstract
AB A set of neurofibromatosis type 1 (NF1) patients was screened for large NF1 gene deletions by comparing patient and parent genotypes at 10 intragenic polymorphic loci. Of 67 patient/parent sets (47 new mutation patients and 20 familial cases), five (7.5%) showed loss of heterozygosity (LOH), indicative of NF1 gene deletion. These five patients did not have severe NF1 manifestations, mental retardation, or dysmorphic features, in contrast to previous reports of large NF1 deletions. All five deletions were de novo and occurred on the maternal chromosome. However, two patients showed partial LOH, consistent with somatic mosaicism for the deletion, suggesting that mosaicism may be more frequent in NF1 than previously recognised (and may have bearing on clinical severity). We suggest that large NF1 deletions (1) are not always associated with unusual clinical features, (2) tend to occur more frequently on maternal alleles, and (3) are an important mechanism for constitutional and somatic mutations in NF1 patients.