The University of Southampton
University of Southampton Institutional Repository

Different mutations in the NF1 gene are associated with Neurofibromatosis-Noonan syndrome (NFNS)

Different mutations in the NF1 gene are associated with Neurofibromatosis-Noonan syndrome (NFNS)
Different mutations in the NF1 gene are associated with Neurofibromatosis-Noonan syndrome (NFNS)
The association of the Noonan phenotype with neurofibromatosis type 1 (NF1) was first noted by Allanson et al. [Am J Med Genet 1985;21:457-462.] and 30 further cases have subsequently been reported. It has been suggested that this phenotype is more common than previously appreciated, as Colley et al. [Clin Genet 1996;49:59-64.] examined 94 sequentially identified patients with NF1 from their genetic register and found Noonan features in 12. A 3-bp deletion of exon 17 of the NF1 neurofibromin gene was described in one family by Carey et al. [Proc Greenwood Genet Center 1997;17:52-53]. However, it remains unclear whether Neurofibromatosis-Noonan syndrome (NFNS) represents a form of NF1 (with mutations in the NF1 neurofibromin gene) or a separate syndrome. We have used a new, rapid sequence analysis technique-comparative sequence analysis (CSA)-to examine the NF1 gene in six patients with NFNS. None of the six patients had the previously identified mutation, nor did we observe other mutations within this exon. However, two other mutations were found: in exon 25, a 3-bp deletion 4312 del GAA, and in exon 23-2, a 2-bp insertion 4095 ins TG. The PTPN11 gene, now known to cause over 50% of Noonan syndrome was also examined in four cases of NFNS, and no mutations were found. These results show that NFNS can in some cases result from different mutations in the NF1 gene and therefore represents a variant form of NF1.
neurofibromatosis, noonan, mutation, sequencing
1552-4825
1-8
Baralle, Diana
faac16e5-7928-4801-9811-8b3a9ea4bb91
Mattocks, Chris
d42ed851-1c39-41f7-b23f-2907dc798849
Kalidas, Kamini
55da1d9d-cd85-48af-a9de-bdf08e38b1d8
Elmslie, Frances
d03e4b3d-89cd-4780-888e-ea55bce39e0a
Whittaker, Joanne
9cba2b30-0004-49f7-8c72-b908cdee6c85
Lees, Melissa
f6e4350a-f8f5-4162-81c5-510c1edc925a
Ragge, Nicola
fa00d824-4a8a-4c2a-8986-cc6b4bc784ee
Patton, Michael A.
6a9dcfa4-8434-4102-9b2b-6ab4d510a04d
Winter, Robin M.
b917c5da-9ec6-4fd4-ac2e-ed475c3675a7
ffrench-Constant, Charles
e9a015d3-a5b8-4789-bd19-d21d7dcabf77
Baralle, Diana
faac16e5-7928-4801-9811-8b3a9ea4bb91
Mattocks, Chris
d42ed851-1c39-41f7-b23f-2907dc798849
Kalidas, Kamini
55da1d9d-cd85-48af-a9de-bdf08e38b1d8
Elmslie, Frances
d03e4b3d-89cd-4780-888e-ea55bce39e0a
Whittaker, Joanne
9cba2b30-0004-49f7-8c72-b908cdee6c85
Lees, Melissa
f6e4350a-f8f5-4162-81c5-510c1edc925a
Ragge, Nicola
fa00d824-4a8a-4c2a-8986-cc6b4bc784ee
Patton, Michael A.
6a9dcfa4-8434-4102-9b2b-6ab4d510a04d
Winter, Robin M.
b917c5da-9ec6-4fd4-ac2e-ed475c3675a7
ffrench-Constant, Charles
e9a015d3-a5b8-4789-bd19-d21d7dcabf77

Baralle, Diana, Mattocks, Chris, Kalidas, Kamini, Elmslie, Frances, Whittaker, Joanne, Lees, Melissa, Ragge, Nicola, Patton, Michael A., Winter, Robin M. and ffrench-Constant, Charles (2003) Different mutations in the NF1 gene are associated with Neurofibromatosis-Noonan syndrome (NFNS). American Journal of Medical Genetics part A, 119A (1), 1-8. (doi:10.1002/ajmg.a.20023).

Record type: Article

Abstract

The association of the Noonan phenotype with neurofibromatosis type 1 (NF1) was first noted by Allanson et al. [Am J Med Genet 1985;21:457-462.] and 30 further cases have subsequently been reported. It has been suggested that this phenotype is more common than previously appreciated, as Colley et al. [Clin Genet 1996;49:59-64.] examined 94 sequentially identified patients with NF1 from their genetic register and found Noonan features in 12. A 3-bp deletion of exon 17 of the NF1 neurofibromin gene was described in one family by Carey et al. [Proc Greenwood Genet Center 1997;17:52-53]. However, it remains unclear whether Neurofibromatosis-Noonan syndrome (NFNS) represents a form of NF1 (with mutations in the NF1 neurofibromin gene) or a separate syndrome. We have used a new, rapid sequence analysis technique-comparative sequence analysis (CSA)-to examine the NF1 gene in six patients with NFNS. None of the six patients had the previously identified mutation, nor did we observe other mutations within this exon. However, two other mutations were found: in exon 25, a 3-bp deletion 4312 del GAA, and in exon 23-2, a 2-bp insertion 4095 ins TG. The PTPN11 gene, now known to cause over 50% of Noonan syndrome was also examined in four cases of NFNS, and no mutations were found. These results show that NFNS can in some cases result from different mutations in the NF1 gene and therefore represents a variant form of NF1.

This record has no associated files available for download.

More information

Published date: 15 May 2003
Keywords: neurofibromatosis, noonan, mutation, sequencing

Identifiers

Local EPrints ID: 59466
URI: http://eprints.soton.ac.uk/id/eprint/59466
ISSN: 1552-4825
PURE UUID: 52fccde8-116a-4076-84b8-fd8b2c513d66
ORCID for Diana Baralle: ORCID iD orcid.org/0000-0003-3217-4833

Catalogue record

Date deposited: 05 Sep 2008
Last modified: 09 Jan 2022 03:27

Export record

Altmetrics

Contributors

Author: Diana Baralle ORCID iD
Author: Chris Mattocks
Author: Kamini Kalidas
Author: Frances Elmslie
Author: Joanne Whittaker
Author: Melissa Lees
Author: Nicola Ragge
Author: Michael A. Patton
Author: Robin M. Winter
Author: Charles ffrench-Constant

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×