Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

Ultra-deep amplicon sequencing indicates absence of low-grade mosaicism with normal cells in patients with type-1 NF1 deletions

Summerer, Anna, Schäfer, Eleonora, Mautner, Victor-Felix, Messiaen, Ludwine, Cooper, David N. and Kehrer-Sawatzki, Hildegard 2019. Ultra-deep amplicon sequencing indicates absence of low-grade mosaicism with normal cells in patients with type-1 NF1 deletions. Human Genetics 138 (1) , pp. 73-81. 10.1007/s00439-018-1961-5
Item availability restricted.

[img] PDF - Accepted Post-Print Version
Restricted to Repository staff only until 20 November 2019 due to copyright restrictions.

Download (295kB)

Abstract

Different types of large NF1 deletion are distinguishable by breakpoint location and potentially also by the frequency of mosaicism with normal cells lacking the deletion. However, low-grade mosaicism with fewer than 10% normal cells has not yet been excluded for all NF1 deletion types since it is impossible to assess by the standard techniques used to identify such deletions, including MLPA and array analysis. Here, we used ultra-deep amplicon sequencing to investigate the presence of normal cells in the blood of 20 patients with type-1 NF1 deletions lacking mosaicism according to MLPA. The ultra-deep sequencing entailed the screening of 96 amplicons for heterozygous SNVs located within the NF1 deletion region. DNA samples from three previously identified patients with type-2 NF1 deletions and low-grade mosaicism with normal cells as determined by FISH or microsatellite marker analysis were used to validate our methodology. In these type-2 NF1 deletion samples, proportions of 5.3%, 6.6% and 15.0% normal cells, respectively, were detected by ultra-deep amplicon sequencing. However, using this highly sensitive method, none of the 20 patients with type-1 NF1 deletions included in our analysis exhibited low-grade mosaicism with normal cells in blood, thereby supporting the view that the vast majority of type-1 deletions are germline deletions.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Springer
ISSN: 0340-6717
Date of First Compliant Deposit: 17 December 2018
Date of Acceptance: 20 November 2018
Last Modified: 02 Jul 2019 15:51
URI: http://orca.cf.ac.uk/id/eprint/117704

Actions (repository staff only)

Edit Item Edit Item

Downloads

Downloads per month over past year

View more statistics