Comprehensive variant spectrum of the CNGA3 gene in patients affected by achromatopsia

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064165%3A_____%2F22%3A10443898" target="_blank" >RIV/00064165:_____/22:10443898 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11110/22:10443898

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=Q7u8BGSZsF" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=Q7u8BGSZsF</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/humu.24371" target="_blank" >10.1002/humu.24371</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Comprehensive variant spectrum of the CNGA3 gene in patients affected by achromatopsia

Popis výsledku v původním jazyce

Achromatopsia (ACHM) is a congenital cone photoreceptor disorder characterized by impaired color discrimination, low visual acuity, photosensitivity, and nystagmus. To date, six genes have been associated with ACHM (CNGA3, CNGB3, GNAT2, PDE6C, PDE6H, and ATF6), the majority of these being implicated in the cone phototransduction cascade. CNGA3 encodes the CNGA3 subunit of the cyclic nucleotide-gated ion channel in cone photoreceptors and is one of the major disease-associated genes for ACHM. Herein, we provide a comprehensive overview of the CNGA3 variant spectrum in a cohort of 1060 genetically confirmed ACHM patients, 385 (36.3%) of these carrying &quot;likely disease-causing&quot; variants in CNGA3. Compiling our own genetic data with those reported in the literature and in public databases, we further extend the CNGA3 variant spectrum to a total of 316 variants, 244 of which we interpreted as &quot;likely disease-causing&quot; according to ACMG/AMP criteria. We report 48 novel &quot;likely disease-causing&quot; variants, 24 of which are missense substitutions underlining the predominant role of this mutation class in the CNGA3 variant spectrum. In addition, we provide extensive in silico analyses and summarize reported functional data of previously analyzed missense, nonsense and splicing variants to further advance the pathogenicity assessment of the identified variants.

Název v anglickém jazyce

Comprehensive variant spectrum of the CNGA3 gene in patients affected by achromatopsia

Popis výsledku anglicky

Achromatopsia (ACHM) is a congenital cone photoreceptor disorder characterized by impaired color discrimination, low visual acuity, photosensitivity, and nystagmus. To date, six genes have been associated with ACHM (CNGA3, CNGB3, GNAT2, PDE6C, PDE6H, and ATF6), the majority of these being implicated in the cone phototransduction cascade. CNGA3 encodes the CNGA3 subunit of the cyclic nucleotide-gated ion channel in cone photoreceptors and is one of the major disease-associated genes for ACHM. Herein, we provide a comprehensive overview of the CNGA3 variant spectrum in a cohort of 1060 genetically confirmed ACHM patients, 385 (36.3%) of these carrying &quot;likely disease-causing&quot; variants in CNGA3. Compiling our own genetic data with those reported in the literature and in public databases, we further extend the CNGA3 variant spectrum to a total of 316 variants, 244 of which we interpreted as &quot;likely disease-causing&quot; according to ACMG/AMP criteria. We report 48 novel &quot;likely disease-causing&quot; variants, 24 of which are missense substitutions underlining the predominant role of this mutation class in the CNGA3 variant spectrum. In addition, we provide extensive in silico analyses and summarize reported functional data of previously analyzed missense, nonsense and splicing variants to further advance the pathogenicity assessment of the identified variants.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30101 - Human genetics

Projekt

<a href="/cs/project/NU20-07-00182" target="_blank" >NU20-07-00182: Dystrofie sítnice dětského věku; multidisciplinární péče s novými přístupy k urychlení molekulární diagnostiky a odhalování mechanizmů onemocnění</a><br>

Návaznosti

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

Rok uplatnění

2022

Kód důvěrnosti údajů

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

Název periodika

Human Mutation

ISSN

1059-7794

e-ISSN

1098-1004

Svazek periodika

43

Číslo periodika v rámci svazku

7

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

27

Strana od-do

832-858

Kód UT WoS článku

000782385300001

EID výsledku v databázi Scopus

2-s2.0-85129080727