Two Czech patients with familial adenomatous polyposis presenting mosaicism in APC gene

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064165%3A_____%2F19%3A10399004" target="_blank" >RIV/00064165:_____/19:10399004 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11110/19:10399004

Result on the web

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=KIQGc-mkWh" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=KIQGc-mkWh</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.4149/neo_2018_180731N559" target="_blank" >10.4149/neo_2018_180731N559</a>

Result language

angličtina

Original language name

Two Czech patients with familial adenomatous polyposis presenting mosaicism in APC gene

Original language description

During standard molecular diagnostic procedure, two Czech families with APC (Adenomatous polyposis coli gene) mosaicism have been detected. A woman with attenuated familial adenomatous polyposis (AFAP, OMIM #175100) was recently inspected by next generation sequencing. Standard bioinfonnatics pipeline, restricted to variants with at least 20% of reads (for germline variants) would miss mutation p.G1412X (NM_000038.5) present in 17% of reads. This novel variant was not present in any of her two children. Another woman with a clinical manifestation of attenuated PAP was tested 16 years ago without conclusive APC mutation found when denaturing gradient gel electrophoresis (DGGE), protein truncation test (PTT) multiplex ligation probe amplification (MLPA) and direct Sanger sequencing were applied. Recent inspection of her son showed clear mutation p.Q1062X (NM_000038.5, NP_000029.2) leading to premature stop codon. This fording led to re-evaluation of this protein position in his mother and detection of mosaicism (11% of allele, 22% of heterozygous cells in blood), which was primarily overlooked. Mutations in both patients were confirmed by allele-specific real time PCR (AS qPCR). In both index patients it was possible to detect and quantify the mosaic allele in biological samples of polyps, adjacent colonic mucosa and buccal swabs. In cases of sporadic appearance of FAP, besides blood we plan to preferably inspect also other samples, where mosaic fraction might be under detection limit of bioinformatics pipelines (&lt;3%). For our future routine NGS sequencing analysis we will apply our in-house somatic variant detection pipeline to minimize the false negative calls when genes with high level of de-novo mutations are analyzed.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10600 - Biological sciences

Project

<a href="/en/project/GBP302%2F12%2FG157" target="_blank" >GBP302/12/G157: Dynamics and Organization of Chromosomes in the Cell Cycle and during Differentiation under Normal and Pathological Conditions</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2019

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Neoplasma

ISSN

0028-2685

e-ISSN

—

Volume of the periodical

66

Issue of the periodical within the volume

2

Country of publishing house

SK - SLOVAKIA

Number of pages

7

Pages from-to

294-300

UT code for WoS article

000465160800017

EID of the result in the Scopus database

2-s2.0-85063294682