Clinical impact of variants in non-coding regions of SHOX – Current knowledge

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00098892%3A_____%2F22%3A10157439" target="_blank" >RIV/00098892:_____/22:10157439 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61989592:15110/22:73609738

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S0378111922000579?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0378111922000579?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.gene.2022.146238" target="_blank" >10.1016/j.gene.2022.146238</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Clinical impact of variants in non-coding regions of SHOX – Current knowledge

Popis výsledku v původním jazyce

The short stature homeobox-containing (SHOX) is the most frequently analysed gene in patients classified as short stature patients (ISS) or diagnosed with Leri-Weill dyschondrosteosis (LWD), Langer mesomelic dysplasia (LMD), or Madelung deformity (MD). However, clinical testing of this gene focuses primarily on single nucleotide variants (SNV) in its coding sequences and copy number variants (CNV) overlapping SHOX gene. This review summarizes the clinical impact of variants in noncoding regions of SHOX. Recent findings: CNV extending exclusively into the regulatory elements (i.e., not interrupting the coding sequence) are found more frequently in downstream regulatory elements of SHOX. Further, duplications are more frequent than deletions. Interestingly, downstream duplications are more common than deletions in patients with ISS or LWD but no such differences exist for upstream CNV. Moreover, the presence of specific CNVs in the patient population suggests the involvement of additional unknown factors. Some of its intronic variants, notably NM_000451.3(SHOX):c.-9delG and c.-65C>A in the 5'UTR, have unclear clinical roles. However, these intronic SNV may increase the probability that other CNV will arise de novo in the SHOX gene based on homologous recombination or incorrect splicing of mRNA. Summary: This review highlights the clinical impact of noncoding changes in the SHOX gene and the need to apply new technologies and genotype-phenotype correlation in their analysis.

Název v anglickém jazyce

Clinical impact of variants in non-coding regions of SHOX – Current knowledge

Popis výsledku anglicky

The short stature homeobox-containing (SHOX) is the most frequently analysed gene in patients classified as short stature patients (ISS) or diagnosed with Leri-Weill dyschondrosteosis (LWD), Langer mesomelic dysplasia (LMD), or Madelung deformity (MD). However, clinical testing of this gene focuses primarily on single nucleotide variants (SNV) in its coding sequences and copy number variants (CNV) overlapping SHOX gene. This review summarizes the clinical impact of variants in noncoding regions of SHOX. Recent findings: CNV extending exclusively into the regulatory elements (i.e., not interrupting the coding sequence) are found more frequently in downstream regulatory elements of SHOX. Further, duplications are more frequent than deletions. Interestingly, downstream duplications are more common than deletions in patients with ISS or LWD but no such differences exist for upstream CNV. Moreover, the presence of specific CNVs in the patient population suggests the involvement of additional unknown factors. Some of its intronic variants, notably NM_000451.3(SHOX):c.-9delG and c.-65C>A in the 5'UTR, have unclear clinical roles. However, these intronic SNV may increase the probability that other CNV will arise de novo in the SHOX gene based on homologous recombination or incorrect splicing of mRNA. Summary: This review highlights the clinical impact of noncoding changes in the SHOX gene and the need to apply new technologies and genotype-phenotype correlation in their analysis.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30101 - Human genetics

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2022

Kód důvěrnosti údajů

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

Název periodika

Gene

ISSN

0378-1119

e-ISSN

1879-0038

Svazek periodika

818

Číslo periodika v rámci svazku

April

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

8

Strana od-do

146238

Kód UT WoS článku

000750792500008

EID výsledku v databázi Scopus

2-s2.0-85123681752