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PMID: 9643287 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Constitutional and mosaic large NF1 gene deletions in neurofibromatosis type 1.

Journal of medical genetics ·Vol. 35 ·No. 6 ·1998-06-00 ·Pages 468-71

Rasmussen SA, Colman SD, Ho VT, Abernathy CR, Arn PH, Weiss L, Schwartz C, Saul RA, Wallace MR

Abstract

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.

MeSH Terms
Adult Centromere Child Exons Female Gene Deletion Genes, Neurofibromatosis 1 Genotype Humans Intellectual Disability/genetics Introns Male Mosaicism Neurofibromatosis 1/genetics Nuclear Family Pedigree Polymerase Chain Reaction Polymorphism, Restriction Fragment Length Telomere/genetics
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Rasmussen S A
Department of Pediatrics, University of Florida College of Medicine, Gainesville 32610-0296, USA.
Colman S D
Ho V T
Abernathy C R
Arn P H
Weiss L
Schwartz C
Saul R A
Wallace M R
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Article Info
Journal
Journal of medical genetics
Abbr.
J Med Genet
ISSN
0022-2593
DOI
10.1136/jmg.35.6.468
Published
1998-06-00
Pages
468-71
Language
English
Region
England
NLM ID
2985087R
PMCID
PMC1051340
Subset
IM
Grants
NCI NIH HHS · F32CA72199 · United States
NINDS NIH HHS · R29NS31550 · United States
NCI NIH HHS · T32CA09126 · United States
External Links
PubMed source DOI: 10.1136/jmg.35.6.468 PMC Full Text View journal details
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