Targeted long-read sequencing identified a causal structural variant in X-linked nephrogenic diabetes insipidus

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00669806%3A_____%2F24%3A10474237" target="_blank" >RIV/00669806:_____/24:10474237 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11140/24:10474237

Result on the web

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

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1186/s12920-024-01801-1" target="_blank" >10.1186/s12920-024-01801-1</a>

Result language

angličtina

Original language name

Targeted long-read sequencing identified a causal structural variant in X-linked nephrogenic diabetes insipidus

Original language description

Background: X-linked nephrogenic diabetes insipidus (NDI) is a rare genetic renal disease caused by pathogenic variants in the AVPR2 gene. Single nucleotide variants and small insertions/deletions in AVPR2 are reliably detected by routine clinical sequencing. Nevertheless, structural variants involving AVPR2 are challenging to identify accurately by conventional genetic testing. Here, we report a novel deletion of AVPR2 in a Czech family identified for the first time by targeted long-read sequencing (T-LRS).Methods: A male proband with X-linked NDI underwent clinical sequencing of the AVPR2 gene that failed and thus indicated possible whole-gene deletion. Therefore, PCR mapping and subsequent targeted long-read sequencing (T-LRS) using a Pacific Biosciences sequencer were applied to search for the suspected deletion. To validate the deletion breakpoints and prove variant segregation in the family with X-linked NDI, Sanger sequencing of the deletion junction was performed. Quantitative real-time PCR was further carried out to confirm the carrier status of heterozygous females.Results: By T-LRS, a novel 7.5 kb deletion of AVPR2 causing X-linked NDI in the proband was precisely identified. Sanger sequencing of the deletion junction confirmed the variant breakpoints and detected the deletion in the probands&apos; mother, maternal aunt, and maternal cousin with X-linked NDI. The carrier status in heterozygous females was further validated by quantitative real-time PCR.Conclusions: Identifying the 7.5 kb deletion gave a precise molecular diagnosis for the proband, enabled genetic counselling and genetic testing for the family, and further expanded the spectrum of structural variants causing X-linked NDI. Our results also show that T-LRS has significant potential for accurately identifying putative structural variants.

Czech name

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Czech description

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Type

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

CEP classification

—

OECD FORD branch

30101 - Human genetics

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2024

Confidentiality

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

Name of the periodical

BMC Medical Genomics

ISSN

1755-8794

e-ISSN

1755-8794

Volume of the periodical

17

Issue of the periodical within the volume

1

Country of publishing house

GB - UNITED KINGDOM

Number of pages

7

Pages from-to

29

UT code for WoS article

001157246700004

EID of the result in the Scopus database

2-s2.0-85182845450